Hudson Institute of Medical Research, 2016 Annual Report by Hudson Institute of Medical Research

UNEXPECTED DISCOVERIES 2016 ANNUAL REPORT

Front cover: Acriflavine bottle from the collection of the Geoffrey Kaye Museum of Anaesthetic History (Australian and New Zealand College of Anaesthetists).

[ OUR MISSION ]

Our mission is to capitalise on our multidisciplinary research strengths, academic and health partnerships, and to provide transformative and innovative solutions to major health problems. [ OUR VISION ]

We strive to enhance human health and quality of life through groundbreaking collaborative medical research discoveries and innovation, to ensure a direct impact on the community. [ OUR CENTRES ]

Centre for Cancer Research

Centre for Endocrinology and Metabolism

Centre for Genetic Diseases

Centre for Innate Immunity and Infectious Diseases

Centre for Reproductive Health

The Ritchie Centre

2016 ANNUAL REPORT / 1

AT A GLANCE

ABOUT US

COLLABORATIONS

OUR DISCOVERIES IMPACT

BOARD CHAIR’S REPORT

DIRECTOR’S REPORT CENTRE REPORTS

Centre for Cancer Research

Centre for Endocrinology and Metabolism

Centre for Genetic Diseases

Centre for Innate Immunity and Infectious Diseases

Centre for Reproductive Health

The Ritchie Centre RESEARCH HIGHLIGHTS

WWI antiseptic could be key to fighting 21st century viral infections

Breakthrough for lung cancer and emphysema offers hope to patients

Australian-first service to help children with brain tumours

Hope for bladder cancer patients

World first – a way forward for a hidden condition

Non-invasive swab test for endometrial cancer

Findings may help women struggling with fertility

PUBLICATIONS

TECHNOLOGY PLATFORMS Launch of the Cell Therapies Platform and Miltenyi Biotec Cell Therapy Centre of Excellence

MHTP RESEARCH WEEK 2016

COMMERCIALISATION AND BUSINESS DEVELOPMENT OUR PEOPLE

Early career researchers

Students

Gender equity

2016 INSTITUTE SPEAKERS

SERVICE TO THE SCIENTIFIC COMMUNITY

OUR COMMUNITY OUR SUPPORTERS

Fielding Foundation

Julian’s story

Thank you to our supporters

Cycling for vital equipment

BOARD OF DIRECTORS

ORGANISATIONAL STRUCTURE

100

FINANCIAL SNAPSHOT

2 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Hudson Institute at a glance

303

183

STAFF

STUDENTS

333

DISEASES IMPACTED BY OUR RESEARCH

RESEARCH PUBLICATIONS

2016 ANNUAL REPORT / 3

About us

Partnerships

Hudson Institute is a leading Australian medical research institute located in the heart of the Monash Health Translation Precinct (MHTP) in Clayton, Victoria. We bring together more than 450 brilliant scientific minds to unlock the mysteries of the human body and enhance human health.

Our partnership with Monash Health (Victoria’s largest healthcare network) and Monash University (Australia’s largest university) to form the Monash Health Translation Precinct, enables us to focus our discoveries on solving the most pressing health needs within our community and Australia.

Our 51 research laboratories are clustered into six specialist centres and conduct both basic and clinical research across cancer, innate immunity and infectious diseases, and women’s and babies’ health.

A strong network of more than 150 leading Australian and international scientific and clinical collaborators support our work and ensure that the impact of our research is global.

We embrace an open structure encouraging collaboration between disciplines, empowering our scientists to examine problems from a wide range of perspectives and sparking out-of-the-box approaches to discovery.

We also partner with Australian and international biotechnology and pharmaceutical companies to ensure our discoveries reach patients, translating to real-world outcomes.

Our history

Translational Research Facility

Two of Australia’s most trusted names in medical research, Prince Henry’s Institute of Medical Research and Monash Institute of Medical Research, merged in 2014 to form Hudson Institute of Medical Research. Combined, we have more than 75 years’ experience in research discoveries for Australia and beyond. Our institute is named after Professor Bryan Hudson, the Founding Director of Prince Henry’s Institute and Founding Chair of the Department of Medicine at Monash University.

Unique in Australia, the Translational Research Facility (TRF) co-locates clinicians and researchers within a purpose-built space, including a Clinical Trials Centre and technology platforms, ensuring our workflow is focused on meeting clinical needs and that our breakthrough discoveries are seamlessly transferred into clinical trials and patient care. The 8-bed, 21-chair Clinical Trials Centre within the TRF is directly linked by a walk-through bridge to Monash Health. This proximity supports the movement of discoveries from initial phase I testing through to phase IV primary health trials. This dynamic interchange between the laboratory and clinic ensures our research responds to the greatest health challenges of the 21st century.

Monash Health Translation Precinct Partners

4 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Collaborations

Adelaide, Australia Brisbane, Australia Canberra, Australia Darwin, Australia Melbourne, Australia Perth, Australia Sydney, Australia Graz, Austria Brussels, Belgium Leuven, Belgium Sao Paulo, Brazil Edmonton, Canada Toronto, Canada Beijing, China Chengdu, China Hangzhou, China Shanghai, China Wuhan, China Aarhus, Denmark Copenhagen, Denmark Cambridge, England Hinxton, England London, England Newcastle, England Oxford, England Warwick, England Turku, Finland Amiens, France Montpellier, France Paris, France

Bonn, Germany Cologne, Germany Freiburg, Germany Giessen , Germany Kiel, Germany Munich, Germany Makassar, Indonesia Dublin, Ireland Ness Ziona, Israel Florence, Italy Padua, Italy Rome, Italy Himeji, Japan Kanazawa, Japan Moroyama, Japan Osaka, Japan Sendai, Japan Suita, Japan Tokyo, Japan Leiden, Netherlands Nijmegen, Netherlands Utrecht, Netherlands Otago, New Zealand Lisbon, Portugal Madinah, Saudi Arabia Thuwal, Saudi Arabia Aberdeen, Scotland Edinburgh, Scotland Singapore, Singapore Madrid, Spain

Gothenburg, Sweden Solna, Sweden Geneva, Switzerland Boston, MA, USA Cincinnati, OH, USA Clay Center, NE, USA Cleveland, OH, USA Coralville, IA, USA Dallas, TX, USA Detroit, MI, USA Greenville, SC, USA Los Angeles, CA, USA Madison, WI, USA Minneapolis, MN, USA New Haven, CT, USA New York City, NY, USA Philadelphia, PA, USA Pittsburgh, PA, USA Providence, RI, USA Pullman, WA, USA Raleigh, NC, USA Salt Lake City, UT, USA San Francisco, CA, USA Seattle, WA, USA Silver Spring, MD, USA St Louis, MO, USA Waltham, MA, USA Washington, DC, USA West Lafayette, IN, USA Cardiff, Wales

2016 ANNUAL REPORT / 5

Our discoveries impact

Cancer

HIV

Baby and children’s health

Bladder cancer

Human metapneumovirus

Birth asphyxia

Bowel cancer

Inflammatory bowel disease

Bronchopulmonary dysplasia

Breast cancer

Influenza

Cerebral palsy

Cancers of the female reproductive tract

Respiratory syncytial virus

Epilepsy

Systemic lupus erythematosus

Intrauterine growth restriction

Endocrine cancers

Vocal cord dysfunction

Endometrial cancer

Zika virus

Neonatal respiratory distress syndrome

Gastrointestinal cancer Leukaemia and lymphomas

Placental development and dysfunction

Lung cancer

Women’s and reproductive health

Ovarian cancer

Assisted reproductive technologies

Paediatric cancer

Disorders of sex development

Pancreatic cancer

Disorders of testicular development

Testicular cancer

Egg and sperm quality

Thyroid cancer

Endometriosis

Other areas

Failure of spermatogenesis

Brain and blood

Immunity and infectious diseases

Female reproductive tract infections, cancers and inflammatory diseases

Cardiovascular disease

Arthritis

Fibroids

Clinical endocrinology research

Asthma

Infertility and contraception

Epigenetics

Chlamydia

IVF

Genetic diseases

Chronic inflammatory diseases

Male reproductive health

Germ cell development

Chronic obstructive pulmonary disease

Parkinson’s disease

Metabolic bone disease

Pelvic organ prolapse

Mitochondrial biology

Gastritis

Pre-eclampsia

Mitochondrial epigenetics

Helicobacter pylori

Premature ovarian failure

Mitochondrial genetics

Herpes simplex virus

Testicular inflammation

Mitochondrial mutations and disease

Premature birth Pulmonary hypertension SIDS Sleep-disordered breathing

Cerebral palsy

6 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Board chair’s report [ DR BOB EDGAR ]

The past year has been one of the greatest in Hudson Institute’s combined 76-year history. The official opening of the Monash Health Translation Precinct’s Translational Research Facility (TRF) in March marked the beginning of a new era that is already defining translational research. The TRF was substantially federally funded thanks to $87.5 million from the government, along with financial contributions from Hudson Institute and Monash University, and land contributions from Monash Health. By combining laboratory and translational research with a dedicated Clinical Trials Centre, this unique facility is fast-tracking our discoveries directly to patients, and cementing the Monash precinct as an Australian leader in translational research. In 2016, collaborations in this unique space produced outstanding outcomes. Several clinical trials and studies are underway in collaboration with Monash Health

clinicians, including a study that may change the dietary advice given to pregnant women and a study to determine a world-first early diagnostic test for lung cancer and emphysema. Commercial investments, such as the research collaboration signed between Hudson Institute, Monash University and Roche in November, are becoming increasingly important as part of the funding mix for independent medical research institutes. They complement and advance Hudson Institute’s existing intellectual property and outstanding record of basic and clinical research. While celebrating our success, I must draw attention to the challenging funding climate we work in. The majority of scientists looking to take discoveries to the clinic encounter the ‘valley of death’, where promising research becomes stalled between discovery and commercial product due to funding gaps.

The federal government’s new $1.1 billion National Innovation and Science Agenda, announced in 2016, can be an important step forward in addressing some of these challenges. The suite of measures includes a $500 million partnership with industry to help commercialise biomedical discoveries into real-life healthcare solutions. We will watch, with interest, the outcomes of this landmark investment. Long-term success in medical research requires foresight, ingenuity and sound management. Our vision as a board is to support our researchers to stay at the top of their game while pushing the boundaries of discovery. I am pleased to report that Hudson Institute is well-placed to navigate the pressures and challenges of our sector. Our board underwent some significant changes during the year. I wish to thank our longstanding board directors Mrs Jane Bell, Ms Jennifer Anne Joiner and Mr John Weste, who retired in 2016, for their contributions over many years.

2016 ANNUAL REPORT / 7

We welcomed three new board directors in 2016: Mr Nigel Garrard, Mr Andrew Leyden and Mrs Zita Peach; and thank them for contributing their time and expertise. Monash Healthâ&#x20AC;&#x2122;s Chief Medical Officer, Professor Erwin Loh, joined the board as an observer during the year. Monash Health is a highly valued precinct and clinical partner of Hudson Institute. Prof Loh brings a unique mix of expertise in medicine, management and law, and extensive knowledge about the health needs of our community. I am extremely grateful for his support. Finally, thank you to Hudson Instituteâ&#x20AC;&#x2122;s Emeritus Director and Distinguished Scientist, Professor Henry Burger AO, who retired as a Member, for his significant contributions over a number of years. We welcomed Distinguished Scientist Professor John (Jock) Findlay in his place and look forward to benefiting from his scientific experience and guidance.

Long-term success in medical research requires foresight, ingenuity and sound management. Our vision as a board is to support our researchers to stay at the top of their game while pushing the boundaries of discovery. To the lifeblood of Hudson Institute, the many wonderful individuals and organisations whose generosity provides the financial support needed for our researchers to continue their discoveries, I express my sincere gratitude. These organisations are listed on page 76.

Dr Bob Edgar Board chair Hudson Institute of Medical Research

8 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Director’s report [ PROFESSOR BRYAN WILLIAMS ]

It has been a memorable year at Hudson Institute of Medical Research as we consolidated and strengthened our position as a premier Australian independent medical research institute across basic, translational and clinical research. Henry Ford said, “Coming together is a beginning, keeping together is progress and working together is success.” Hudson Institute’s success is a sum of all of our parts— researchers, staff, collaborations and partnerships. The impact of our work on human health and in our sector resonated widely in 2016. Our scientists were awarded more than $10 million in government research grants, published 333 publications, made major research advances and commenced clinical trials, all building on our 76-year contribution to discoveries in our community, across Australia and the globe.

We also signed major commercial deals with pharmaceutical companies, based on discoveries made by our scientists, signalling our shift to translational research and move into drug development. Philanthropic support, in particular, is crucial to our ongoing research success. We are grateful that Melbourne businessperson and philanthropist Mr Peter Fielding, through the 2016 Fielding Innovation Award, supported Associate Professor Marcel Nold to realise the commercial potential of his laboratory’s work. In 2016, the Gandel Foundation committed more than $500 000 in funding for genomics in our technology platforms. This vital funding will allow us to create a Gandel Genomics Health Research Program to rapidly transition medical discoveries into improved healthcare using the latest genomic technologies. I very much look forward to reporting on the

progress and impact of this worldleading technology. Our newly established Centre for Functional Genomics, led by Dr Joseph Rosenbluh who we recruited from the USA jointly with Monash University, will further expand our leadership in precision cancer medicine to find new and more targeted solutions for diseases. We were delighted that, in an uncertain research funding climate, the National Health and Medical Research Council awarded more than $10 million in fellowships and competitive grants to our researchers. Our 2016 awards included a prestigious Young Tall Poppy Science Award, awarded to Dr Maria Kaparakis-Liaskos, for her work on immune responses during Helicobacter infection. Sadly, Dr Kaparakis-Liaskos and esteemed breast cancer researcher Dr Kristy Brown departed the institute at

2016 ANNUAL REPORT / 9

the end of 2016 to take up new university research positions with secured funding. I wish Dr KaparakisLiaskos and Dr Brown the very best in their future endeavours. While endlessly rewarding, a career in medical research can be a difficult path for young scientific minds to carve. Government grant funding has remained largely static and the pot of money is not increasing in line with the number of researchers reliant on this scarce resource, creating great uncertainty within our workforce. I am grateful to our researchers for their dedication to science and to their families for their support. We will continue to work with government and industry to ensure we continue to attract and retain talented scientists, while securing the future of Australia’s thriving medical research sector and driving science innovation. In addition to vital government support, our research is only made possible through the support of

Henry Ford said, “Coming together is a beginning, keeping together is progress and working together is success.” Hudson Institute’s success is a sum of all of our parts—researchers, staff, collaborations and partnerships. foundations, trusts, charities and industry partners. To all of our vital supporters, thank you. I look forward to another year of working together as Hudson Institute. Thank you for being a key part of our success.

Professor Bryan Williams Director and CEO Hudson Institute of Medical Research

10 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Centre for Cancer Research [ CENTRE HEAD: ASSOCIATE PROFESSOR RON FIRESTEIN ]

Our discoveries impact CANCER Bladder cancer Bowel cancer Breast cancer Leukaemia and lymphomas Lung cancer Ovarian cancer Paediatric cancer

Centre for Cancer Research (CCR) scientists tackle the most pressing challenges in the diagnosis and treatment of adult and childhood cancers. The Centre’s goal is to explain the fundamental mechanisms of tumour biology and to use our discoveries for the development of novel cancer therapies and biomarkers (indicators) of cancer.

Prostate and bowel cancer breakthrough brings personalised medicine a step closer Targeted genetic treatment for cancer is a step closer, with a worldfirst clinical trial set to test the effectiveness of a new class of drugs called BET inhibitors in treating prostate and colorectal cancers. A team of clinicians and researchers at Hudson Institute and Monash University was awarded a $2 million Victorian Cancer Agency grant for the innovative project.

The three-year trial will involve 24 patients with stage four prostate cancer or colorectal cancer, for whom all other forms of treatment have failed. Prostate and colorectal cancers are two of the most commonly diagnosed cancers in Australia. More than 3000 men die of prostate cancer and more than 4100 lives are claimed by colorectal cancer every year in Australia. The trial builds on previous work by co-lead of the project and CCR Head, Associate Professor Ron Firestein, which identified a genetic marker that may explain why only some patients respond to BET inhibitors. “BET inhibitors are a relatively new class of cancer drugs that target tumour cells at a genetic level by essentially ‘switching off’ the expression of certain cancer genes,” A/Prof Firestein said. “My research at Genentech in the USA found that patients who express a particular genetic marker,

2016 ANNUAL REPORT / 11

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

long, non-coding RNAs, may respond best to this type of genetic cancer therapy. “This is the first clinical trial to target the treatment to patients with a specific genetic marker.” A/Prof Firestein says the aim of the project is to develop a test that could eventually be used in cancer patients to assess their genetic compatibility with BET inhibitor therapy. Medical oncologist at Monash Health and Monash University Senior Research Fellow, Dr Arun Azad, believes around 50 per cent of prostate and colorectal cancer patients have the RNA biomarker and predicts these patients will respond well to the new class of drug. “We’re ultimately hoping to increase the range of therapeutic options available to prostate and colorectal cancer patients,” added Dr Azad. The team is optimistic about the potential for epigenetic therapies like BET inhibitors.

STUDENTS

“Improving the effectiveness of targeted cancer therapies not only improves survival rates, it also provides more options to patients who invariably develop chemotherapy resistance,” A/Prof Firestein said. Collaborators on this study include Monash University’s Professor Gail Risbridger, Associate Professor Helen Abud, colorectal surgeon Associate Professor Paul McMurrick and Cabrini’s Dr Simon Wilkins.

New therapies targeting the cancer cell’s engine Despite being implicated in more than 50 per cent of cancer tumours, a biochemical pathway called STAT3 has remained elusive to researchers and oncologists. STAT3 is difficult to target with cancer drugs, as high levels detected in the system are correlated with poor survival rates. CCR scientist, Dr Daniel Gough, working with Professor Brendan

31 STAFF

DISEASES IMPACTED BY OUR RESEARCH

Jenkins from CiiiD, has identified a pool of STAT3 that enters the mitochondria, or the ‘powerhouse’, which supplies energy to a cell. From here, STAT3 can control the mitochondria’s key functions and crucially, the growth of cancer tumours. The next step is to see whether currently available cancer drugs are effective in targeting this particular pool of STAT3, providing the potential to intervene before it enters the mitochondria and thus stop the growth of cancer.

Linking inflammation and cancer The Immunohaematology laboratory, led by Dr Ashish Banerjee and Dr George Grigoriadis, is working to understand the role of the cancer regulator protein ‘NIK’ in the growth of lymphoma, a type of blood cancer. The laboratory has successfully generated a sophisticated and

12 / HUDSON INSTITUTE OF MEDICAL RESEARCH

novel model that will enhance our understanding of this important pathway. In addition, Dr Banerjee’s group is investigating the role of a transcription regulator called RelA in inflammation and cancer. Continued collaboration with the Walter and Eliza Hall Institute of Medical Research has enabled a successful NHMRC grant supporting this project, with a publication in preparation.

Dr Ashish Banerjee (Immunohaematology) Dr Kristy Brown (Metabolism and Cancer) Dr Jason Cain (Developmental and Cancer Biology) A/Prof Colin Clyne (Cancer Drug Discovery) Dr Daniel Gough (STAT Cancer Biology) Dr George Grigoriadis (Immunohaematology)

New hope for paediatric solid brain tumour

Prof Terrance Johns (Oncogenic Signalling)

Malignant rhabdoid tumour (MRT) is a rare but devastating paediatric solid cancer that starts in the kidneys or in the brain and can spread to other parts of the body. Children are diagnosed with the disease at an average age of just 15 months.

Dr Anthony Sadler (Cancer and Innate Immunity)

In work published in the prestigious journal Clinical Cancer Research, Dr Jason Cain’s research group has identified a new therapeutic target for MRT.

Distinguished scientist

Dr Cain’s team showed that histone deacetylase inhibitors have profound effects in both inhibiting the growth of these tumours and inducing the process of reverting cancerous tissue to normal tissue.

Australian Lions Childhood Cancer Research Foundation

This work underpinned a successful collaborative NHMRC project grant to next conduct a phase ll clinical trial in patients with paediatric solid tumours, that will see these preclinical research findings implemented into the clinic.

Dr Andrew Stephens (Ovarian Cancer Biomarkers) Prof Bryan Williams (Cancer and Innate Immunity)

Prof Alan Trounson

Our supporters

Bailey’s Day Children’s Cancer Foundation Evans Family Foundation National Breast Cancer Foundation NHMRC Ovarian Cancer Research Foundation United States Department of Defense Victorian Cancer Agency

Research group heads A/Prof Ron Firestein (Cancer Genetics and Functional Genomics) A/Prof Elizabeth Algar (Genetics and Molecular Pathology)

2016 ANNUAL REPORT / 13

Centre for Endocrinology and Metabolism [ CENTRE HEAD: PROFESSOR PETER FULLER AM ]

Our discoveries impact CANCER Breast cancer Endocrine cancers Ovarian cancer Thyroid cancer WOMENâ&#x20AC;&#x2122;S AND REPRODUCTIVE HEALTH Cancers of the female reproductive tract

Centre for Endocrinology and Metabolism (CEM) scientists undertake basic and clinical research to show the impact of the endocrine system on health and disease. Our researchers improve the understanding of hormones in human biology that impact reproductive health, bone health, cardiovascular disease, endocrine cancer and obesity to improve and refine diagnosis, treatment and prevention of disease.

Male reproductive health OTHER Cardiovascular disease Cerebral palsy Clinical endocrinology research Metabolic bone disease

Mobility and muscle mass key for maintaining bone health in cerebral palsy and spina bifida Our researchers have found that immobility is the most significant risk factor for fractures in children and adults with spina bifida. Dr Anne Trinh, a clinical endocrinologist and PhD student working with Associate Professor Fran Milat in the Metabolic Bone Research group, studies the effects of cerebral palsy and spina bifida

on musculoskeletal health from childhood to young adulthood. In a retrospective study of 146 spina bifida patients, ranging from toddlers to adults, Dr Trinh showed that people with spina bifida who couldnâ&#x20AC;&#x2122;t walk independently of a mechanical aid had an increased risk of fracture, highlighting the importance of maintaining mobility in spina bifida. In another study, Dr Trinh examined the relationship between body composition, bone mineral density and fractures in 45 adults with cerebral palsy. This study found that maintaining muscle mass is crucial for good bone health in young adults with cerebral palsy. It also showed for the first time that hypogonadism (a lack of sex steroids, linked to an increased risk of bone fractures) was present in 20 per cent of these patients. Hypogonadism was linked to changes in body composition, including reductions in lean tissue mass and lumbar spine bone mineral

14 / HUDSON INSTITUTE OF MEDICAL RESEARCH

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

density. In addition, low bone mineral density and fractures were found to be common in adults with cerebral palsy. These findings could help researchers and clinicians tailor treatments to patients with cerebral palsy, to help prevent bone fractures that can limit mobility and quality of life. “Fractures can have a devastating impact on already reduced mobility in adults with chronic neurological disease such as cerebral palsy,” Dr Trinh said. “By identifying the importance of muscle and sex steroids in maintaining bone health, treatment can be tailored to reduce fracture risk in these individuals. “This study goes some way to illuminating the functional and endocrine factors behind an increased risk of bone fractures in young people with cerebral palsy.” Dr Trinh and her team are now recruiting patients for a clinical

STUDENTS

trial at Monash Health that will show whether zoledronic acid, which is normally used to treat osteoporosis, can be used in adults with cerebral palsy. Dr Trinh’s work is supported by a grant from Osteoporosis Australia and The Royal Australasian College of Physicians.

Clinician-researchers open Melbourne’s first endocrine hypertension clinic Melbourne’s first endocrine hypertension clinic opened at Monash Health this year under the auspices of CEM clinicianresearchers Dr Jun Yang, Dr Jimmy Shen and Professor Peter Fuller. The clinic is designed to streamline diagnosis for Conn’s syndrome, also known as primary aldosteronism, a common yet underdiagnosed cause of high blood pressure. Conn’s syndrome affects up to 10 per cent of people with high blood pressure and causes more strokes,

30 STAFF

DISEASES IMPACTED BY OUR RESEARCH

heart attacks and heart arrhythmia than ordinary high blood pressure. Many patients with Conn’s syndrome are not properly diagnosed and so are placed on unnecessary medication that does not treat the underlying cause of disease. If detected early, Conn’s syndrome is potentially curable or easily managed with a specific drug. Establishment of the clinic has led to an exponential increase in the number of referrals for the investigation of Conn’s syndrome. The clinic will integrate patient data with laboratory-based research so that cutting-edge science can be incorporated into day-to-day healthcare.

New kidney link for blood disorder medication discovered Thalassaemia major is a genetic disorder that affects the production of haemoglobin and results in severe anaemia. The treatment options

2016 ANNUAL REPORT / 15

for this condition include blood transfusions and bone marrow transplants. Clinician-researcher Dr Phillip Wong is investigating thalassaemia major and other transfusion-dependent haemoglobinopathies (genetic defects resulting in blood disorders), in the Metabolic Bone Research group, led by A/Prof Frances Milat. A cross-sectional study by Dr Wong, examining 152 adults with betathalassaemia major and related conditions, found that a common drug used to remove excess iron that accumulates in the liver could lead to kidney damage. Therapeutic doses of deferasirox, an iron chelator used in patients with these blood conditions who undergo regular transfusions, was linked to hypercalciuria (elevated levels of calcium in the urine). Dr Wongâ&#x20AC;&#x2122;s study recommended further investigation and vigilance with the use of these drugs, as hypercalciuria can lead to impaired kidney function and kidney stones.

Helping patients with heart disease New treatments for patients with heart disease who are at risk of developing heart failure were discovered by Dr Morag Youngâ&#x20AC;&#x2122;s research group, Cardiovascular Endocrinology. The group focuses on the cell signalling processes involved in the cardiac injury and repair that underlies many cardiovascular diseases. Their work, published in the journal Endocrinology, showed that cell signalling initiated by a steroid hormone receptor (the MR) in inflammatory cells within the heart is a major cause of tissue inflammation and formation of fibrotic deposits. This results in poor heart muscle function and other detrimental features of heart failure.

By studying and activating the signalling in MR inflammatory cells of the heart (macrophages) isolated from the heart and aorta, as well as other areas in the body, the team discovered regulation of specific inflammatory signals and fibrotic factors that negatively impact the heart.

Research group heads Prof Peter Fuller AM (Steroid Receptor Biology) Prof Robert McLachlan AM (Clinical Andrology) Clinical A/Prof Frances Milat (Metabolic Bone Research) Dr Peter Stanton (Male Fertility Regulation, jointly with Centre for Reproductive Health) Dr Morag Young (Cardiovascular Endocrinology)

Our supporters Amgen Cerebral Palsy Alliance GlaxoSmithKline Monash Comprehensive Cancer Consortium Monash Health NHMRC Osteoporosis Australia Ovarian Cancer Research Foundation Servier The Endocrine Fellows Foundation, USA The Endocrine Society of Australia The Ian Potter Foundation The Rebecca L. Cooper Medical Research Foundation The Rivkin Center for Ovarian Cancer, USA The Royal Australasian College of Physicians

16 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Centre for Genetic Diseases [ CENTRE HEAD: PROFESSOR JUS ST. JOHN ]

Our discoveries impact WOMEN’S AND REPRODUCTIVE HEALTH Assisted reproductive technologies Egg and sperm quality Infertility OTHER Brain and blood Epigenetics Genetic diseases Germ cell development Mitochondrial biology Mitochondrial epigenetics Mitochondrial genetics Mitochondrial mutations and disease

Scientists in the Centre for Genetic Diseases (CGD) focus on understanding the genetic causes underlying disease. We use innovative reproductive, developmental and stem cell models and state-of the-art analytical approaches to better understand gene inheritance. By understanding genetic mutations, the number of copies of genes and how epigenetic regulators work, we provide a platform to improve clinical practice to prevent lifelong disease.

Scientists rescue poor quality eggs with genetically identical mitochondrial DNA Many women undergoing IVF have eggs that either fail to fertiIise or arrest during very early embryo development—the result of these eggs having low counts of mitochondrial DNA. Research by Professor Jus St. John and his team, in collaboration with commercial partners OvaScience

and colleagues at Harvard University, has shown that supplementing poor quality eggs with genetically identical mitochondrial DNA can increase the chances of achieving a pregnancy and a live birth. The team supplemented an egg that had low counts of mitochondrial DNA with genetically identical material taken from another egg, and demonstrated that these poor quality eggs could be rescued and successfully fertilised. “Not only were we able to show that these eggs could be rescued, we also showed that they produced high quality embryos and were very similar to those embryos generated from normal eggs,” Prof St. John, Head of CGD, said. “We were also able to show that the embryos expressed key genes vital for embryo development and that their gene expression profiles were similar to embryos derived from good quality eggs.” In addition, the scientists discovered that this process of mitochondrial

2016 ANNUAL REPORT / 17

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

supplementation induces an unexpected mitochondrial DNA replication event, which ensures sufficient mitochondrial DNA is present during early embryo development. “Previously, scientists had not realised the importance of mitochondrial DNA to the processes of fertilisation and development. Our results show that it is the amount of mitochondrial DNA that is important,” Prof St. John explained. Data from the study has been presented to authorities that regulate the use of eggs and embryos in the UK and Japan, as well as at international meetings.

Finding will assist new treatments for mitochondrial disorders Defects in mitochondria can cause disease in organs such as the brain, heart and liver. Often there are no

STUDENTS

effective therapies for these patients and the disease is fatal because mitochondria are a vital part of a cell, generating the energy it requires. Dr Matthew McKenzie, Head of the Molecular Basis of Mitochondrial Disease research group, leads work aimed at understanding how things can go wrong in this essential cellular process. A key component of the cell’s energy production pathway is mitochondrial complex I. To function properly, this complex needs to be precisely assembled from 45 parts. Dr McKenzie and collaborators have found that loss of just one of these parts, ND1, disrupts the early stages of mitochondrial complex I assembly. It was also discovered that loss of ND1 impacts on another key component of energy production, mitochondrial complex IV. These findings further the understanding of how defects in mitochondrial complex I may cause disease, and will help in the design of future therapies for mitochondrial disorders.

STAFF

DISEASES IMPACTED BY OUR RESEARCH

Safeguards for preventing genetic mutations during fetal development We inherit mitochondrial DNA from our mothers. Often, it has a number of mutations that, at low levels, tend to be harmless. In this study, led by Prof St. John, scientists developed a preclinical model to understand how these mutations are passed from one generation to the next without becoming harmful. The results, taken over three generations, show that mitochondrial DNA mutations are present in eggs and embryos, but their levels are reduced in our tissues and organs. This research highlights the mechanisms in place during fetal development that restrict the replication and transmission of mutations in other parts of our bodies so that our tissues and organs can function normally.

18 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Key insights into ovary formation and development The development of reproductive organs begins while we are still in the womb. The formation of an ovary or testis is fundamental for determining a babyâ&#x20AC;&#x2122;s gender, supporting lifelong fertility and ensuring enough reproductive sex hormones are produced. Despite this key role, surprisingly little is known about ovarian development, especially during fetal life. Dr Patrick Western, from the Germ Cell Development and Epigenetics group, and his team have developed a new cell-based approach to examine ovary formation that will provide a greater understanding of the cell differentiation events that lead to the formation of ovaries in a fetus. This study provided new insights into the formation of ovarian cells

that will ultimately sustain a baby girlâ&#x20AC;&#x2122;s own egg development and production, as well as her ovary function. This research is essential for the broader understanding of female fertility, ovarian function and female reproductive health.

Research group heads Prof Jus St. John (Mitochondrial Genetics) Dr Matthew McKenzie (Molecular Basis of Mitochondrial Disease) Dr Patrick Western (Germ Cell Development and Epigenetics)

Our supporters Australian Mitochondrial Disease Foundation Australian Pork Limited OvaScience Inc, USA

2016 ANNUAL REPORT / 19

Centre for Innate Immunity and Infectious Diseases [ CENTRE HEAD: PROFESSOR PAUL HERTZOG ]

Our discoveries impact CANCER Breast cancer Endometrial cancer Gastrointestinal cancer (particularly stomach adenocarcinoma and lymphoma) Lung cancer Ovarian cancer Pancreatic cancer IMMUNITY AND INFECTIOUS DISEASES Arthritis Asthma Chlamydia Chronic inflammatory diseases Chronic obstructive pulmonary disease Gastritis Helicobacter pylori Herpes simplex virus HIV Human metapneumovirus Inflammatory bowel disease

Influenza Respiratory syncytial virus Systemic lupus erythematosus Vocal cord dysfunction Zika virus WOMEN’S AND REPRODUCTIVE HEALTH Female reproductive tract infections, cancers and inflammatory diseases

Scientists in the Centre for Innate Immunity and Infectious Diseases (CiiiD) focus on molecules and cells that comprise our innate immune system. We aim to discover how our immune system fights infection, inflammatory diseases and cancer, and to develop new approaches to understanding, preventing, diagnosing and treating these diseases.

Breakthrough for lung disease The Cancer and Immune Signalling laboratory, headed by Professor Brendan Jenkins, discovered that the drug ‘sgp130Fc’ has the ability to halt the progression of lung cancer and emphysema. Combined, these lung diseases claim the lives of 15 000 Australians each year. The study on emphysema, a culmination of six years’ work for the team, including first author and NHMRC Biomedical Fellow Dr Saleela Ruwanpura, was published in the prestigious American Journal

20 / HUDSON INSTITUTE OF MEDICAL RESEARCH

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

of Respiratory and Critical Care Medicine. It follows on from a related study on lung cancer published earlier in 2016 by the team, including first author and PhD student Gavin Brooks, in the top-ranked Cancer Research journal. In both studies, the CiiiD researchers identified that an inflammationcausing molecule, interleukin 6 (IL-6), propels emphysema and lung cancer through a process called trans-signalling. Trans-signalling is the master regulator of the disease process, so it has very important effects on lung disease. Therefore, it is also an attractive target for treatment with drugs such as sgp130Fc. The drug sgp130Fc was developed by CiiiD collaborator Professor Stefan Rose-John from the University of Kiel, to specifically target the process of transsignalling. It is currently being tested in clinical trials for other diseases that use the mechanism of transsignalling, including inflammatory bowel disease. Prof Jenkins’ team

STUDENTS

now believes the drug has clinical potential against lung cancer and emphysema. The Cancer and Immune Signalling laboratory in CiiiD is also working with clinical colleagues at Monash Health, led by Professor Philip Bardin, to analyse the blood samples of lung cancer and emphysema patients in the hope of developing an early detection blood test for both diseases. Lung cancer and emphysema are difficult to detect early, meaning that effective management and treatment for patients with these conditions is compromised. For example, at present, emphysema can only be diagnosed by a CT scan and only long after the disease has begun. This delay means many patients do not receive treatment until the disease has progressed to a severe state, when treatment options are limited. A blood test has the potential to vastly improve survival rates through earlier diagnosis, while sgp130Fc has

36 STAFF

DISEASES IMPACTED BY OUR RESEARCH

the ability to halt the progression of lung cancer and emphysema. Not every patient with emphysema or lung cancer will benefit from this drug, but with clinical trials Prof Jenkins’ team can identify which patients would respond to treatment, and at which stage of the disease they may best respond. Lung cancer is the most common cancer in the world and the leading cause of cancer death in Australia. Emphysema is the major debilitating component of the lethal chronic obstructive pulmonary disease, which is predicted by the World Health Organization to be the thirdleading cause of death worldwide by 2020, behind heart disease and cancer. The team’s research was publicised widely in Victorian and national media.

Pivotal discovery: fighting influenza outbreaks Pandemic influenza outbreaks, such as the 1918 Spanish flu, can have devastating global consequences,

2016 ANNUAL REPORT / 21

yet we still only have limited treatments for these diseases. Research by Associate Professor Ashley Mansell and Dr Michelle Tate of the Pattern Recognition Receptors and Inflammation group, published in the prestigious journal Scientific Reports, has shown that the influenza virus can overstimulate the NLRP3 inflammasome, which causes the body to burn up with infection from the inside, in a socalled ‘cytokine storm’. Their pivotal discovery identifies that blocking the inflammasome at the height of infection with the experimental drug MCC950 can reduce this dangerous inflammatory response. Targeting the inflammasome may have potential as an effective therapeutic approach for lethal influenza infections and addresses an urgent unmet need for flu treatments. The findings from A/Prof Mansell’s and Dr Tate’s study may also be applied to other diseases where the NLRP3 inflammasome plays a critical role, including dengue fever, arthritis and even septic shock.

War on superbugs A team of CiiiD researchers identified that a WWI antiseptic could be used as a front-line drug against viruses and ‘superbugs’. Led by Dr Michael Gantier and Dr Genèvieve Pépin of the Nucleic Acids and Innate Immunity group, the study found that acriflavine, a century-old antiseptic made from a derivative of coal tar, protects against the common cold by triggering an antiviral immune response. The team discovered that acriflavine binds cellular DNA to activate the host immune system and unleash a powerful immune response on a potentially broad range of pathogens. They

believe acriflavine could be a useful tool in the fight against superbug resistance and viral pandemics. Next, the team will use preclinical models to test how acriflavine mobilises the immune system in more virulent infections. The study was published in the prestigious journal Nucleic Acids Research, and publicised in national and international media.

Microbiome key to good health Scientists at the Wellcome Trust Sanger Institute in Cambridge, UK, including Dr Samuel Forster (NHMRC CJ Martin Biomedical Overseas Fellow from the Regulation of Interferon and Innate Signalling group of CiiiD), have grown and catalogued more than 130 bacteria from the human intestine in a study published in Nature. The researchers developed a process to understand how our bacterial ‘microbiome’ helps keep us healthy and how imbalances contribute to complex conditions and diseases such as obesity, inflammatory bowel disease, irritable bowel syndrome and allergies. Dr Forster says, “The extensive database of genomes we have generated from these bacteria is essential for studying which bacteria are present or absent in people with gastrointestinal conditions. Now we can start to design mixtures of therapeutic candidates for use in these diseases.” Dr Forster will return to continue his microbiota research in Melbourne at CiiiD in 2017/18.

A/Prof Richard Ferrero (Gastrointestinal Infection and Inflammation) Dr Michael Gantier (Nucleic Acids and Innate Immunity) Prof Brendan Jenkins (Cancer and Immune Signalling) Dr Maria Kaparakis-Liaskos (Host– Pathogen Interactions) A/Prof Ashley Mansell (Pattern Recognition Receptors and Inflammation)

Our supporters Alliance for Lupus Research Australian Centre for HIV and Hepatitis Virology Research (ACH2) Australian Institute of Policy and Science Australian Research Council (ARC) Bill and Melinda Gates Foundation Cancer Council Victoria CASS Foundation NHMRC The Sylvia and Charles Viertel Charitable Foundation United States Department of Defense United States National Institutes of Health/National Institute of Allergy and Infectious Diseases Victorian Endowment For Science Knowledge and Innovation (veski)

Commercial partners

Research group heads

Cartherics Pty Ltd

Prof Paul Hertzog (Regulation of Interferon and Innate Signalling)

Lateral Pharma Pty Ltd

Prof Philip Bardin (Respiratory and Lung Research)

Pfizer Centers for Therapeutic Innovation

22 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Centre for Reproductive Health [ CENTRE HEAD: PROFESSOR LOIS SALAMONSEN ]

Our discoveries impact CANCER Endometrial cancer Ovarian cancer Testicular cancer WOMEN’S AND REPRODUCTIVE HEALTH Disorders of sex development Disorders of testicular development Endometriosis Failure of spermatogenesis

Lifelong health is determined by external factors that begin exerting their influence prior to conception. Using basic and translational science, researchers in the Centre for Reproductive Health (CRH) seek to answer critical questions about sperm and egg development, early embryo development, implantation of the embryo into the womb, formation of the placenta and nurture of the fetus until birth, and how these affect human life and development.

Fibroids Infertility and contraception Parkinson’s disease Pre-eclampsia Testicular inflammation BABY AND CHILDREN’S HEALTH Intrauterine growth restriction Placental development and dysfunction

Targeting small molecule could stop growth of endometrial cancer Endometrial cancer occurs in the inner lining of the uterus and is the most common gynaecological cancer. In 2016, the disease claimed the lives of around 441 Australian women, with an estimated 2652 new cases diagnosed. Endometrial cancer is one of the most common types of cancer affecting postmenopausal women,

but incidences are increasing in women of child-bearing age. CRH researchers believe blocking a small signalling molecule known as interleukin 11 (IL-11) could reduce tumour growth and spread. Associate Professor Eva Dimitriadis’ Embryo Implantation research group developed a model of endometrial cancer to test the hypothesis around IL-11. Using this model, which mimics the growth of human cancer cells, the researchers were able to show that targeting IL-11 reduces the growth and spread of endometrial cancer tumours. “It’s exciting to find that targeting this small molecule in preclinical stages could help block the growth of endometrial tumours,” said Dr Amy Winship, a postdoctoral researcher in A/Prof Dimitriadis’ laboratory. “There is no screening test for this disease and there is a lack of curative therapies for patients with recurrent or aggressive disease, or for young women wanting to preserve fertility.

2016 ANNUAL REPORT / 23

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

“Our next step will be to test the treatment in a spontaneous preclinical model of endometrial cancer before the work may proceed to clinical trials,” Dr Winship said.

Understanding male contraception Our researchers are investigating the potential use of male hormonal contraceptives. In a paper published in the important clinical journal Human Reproduction, Dr Peter Stanton and his team demonstrated that a vital component of the blood– testis barrier becomes disorganised when male hormonal contraceptives are used effectively for eight weeks. The same effect is also seen in men with testicular disorders that lead to infertility, indicating that maintenance of the blood–testis barrier is important for male fertility. Understanding the way in which male hormonal contraceptives work is key to translating them to clinical use and will allow us to gain insights into the causes of male infertility.

STUDENTS

Male sex development breakthrough Gender is determined at conception and during the development of the fetus. Disorders of sex development, or intersex, may be triggered by genetic disturbances during this development period. A focus of Professor Vincent Harley’s Sex Development laboratory is the ‘SRY’ gene, which is responsible for the initiation of male sex determination in humans, along with the gene that regulates this process, known as ‘SOX9’. Prof Harley and his PhD student, Dimuthi Alankarage, discovered one mechanism by which SOX9 exerts its effects on the testis to maintain a niche among stem cells that in turn promotes the development of sperm. Their discovery was published in the International Journal of Biochemistry & Cell Biology, and has important implications for understanding male infertility.

39 STAFF

DISEASES IMPACTED BY OUR RESEARCH

Embryo–maternal communication for implantation success Dr Hong Nguyen and Professor Lois Salamonsen, in collaboration with Dr David Greening and Professor Richard Simpson from La Trobe University, described an important step in the initiation of pregnancy in the journal Biology of Reproduction. They demonstrated that nanosized extracellular vesicles, released from epithelial stem cells located in the endometrium, contain hormone-specific cargo called exosomes that are taken up by trophoblast cells (the outer cells of the blastocyst, a precursor to an embryo). The vesicles release their cargo into these cells, making the trophoblast more ‘adhesive’, and help the embryo to implant in the endometrium—the first step in creating a healthy pregnancy.

24 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Research group heads

Distinguished scientists

Prof Lois Salamonsen (Endometrial Remodelling)

Prof David de Kretser AC, Distinguished Sir John Monash Professor

Prof David de Kretser AC (Activin Follistatin Biology and Inflammation)

Prof Jock Findlay AO

A/Prof Eva Dimitriadis (Embryo Implantation)

Our supporters

Prof Jock Findlay AO (Ovarian Biology)

Bethlehem Griffiths Research Foundation

Prof Vincent Harley (Sex Development)

Cancer Council Victoria

A/Prof Mark Hedger (Endocrinology and Immunophysiology)

Ferring Pharmaceuticals

CASS Foundation

Dr Joohyung Lee (Brain and Gender)

Merck

Prof Kate Loveland (Testis Development and Male Germ Cell Biology)

Monash IVF Research and Education Foundation

A/Prof Guiying Nie (Implantation and Placental Development)

Rotary Club of Balwyn

Dr Peter Stanton (Male Fertility Regulation, jointly with Centre for Endocrinology and Metabolism)

NHMRC

Society for Reproductive Biology

2016 ANNUAL REPORT / 25

The Ritchie Centre [ CENTRE HEAD: PROFESSOR STUART HOOPER ]

Our discoveries impact IMMUNITY AND INFECTIOUS DISEASES Systemic lupus erythematosus WOMEN’S AND REPRODUCTIVE HEALTH Endometriosis Infertility IVF Pelvic organ prolapse Pre-eclampsia Premature ovarian failure BABY AND CHILDREN’S HEALTH Birth asphyxia Bronchopulmonary dysplasia Cerebral palsy Epilepsy Intrauterine growth restriction Neonatal respiratory distress syndrome Premature birth Pulmonary hypertension SIDS Sleep-disordered breathing

The Ritchie Centre (TRC) is Australia’s premier clinical and research centre for women, pregnancy, newborn babies and children. It adopts a unique and holistic cycle of care from pregnancy through to birth and early childhood. The collaboration between researchers and clinicians at TRC drives the energy and expertise behind finding solutions to the most important problems facing pregnant women and their babies, both in Australia and overseas.

$6 million for research to reduce harm stemming from premature birth Minimising harm to babies exposed to adverse early life events such as premature birth and birth asphyxia is the focus of a research program made possible by a $6.12 million NHMRC grant. Professor Stuart Hooper, Professor Euan Wallace and Professor Peter

Davis from The Royal Woman’s Hospital will lead the five-year program. It will bring together 30 Australian and international experts in the fields of neonatology, physiology and obstetrics, as well as in clinical and basic sciences, to find ways to minimise harm stemming from events that occur shortly before or after birth. “Adverse early life events like premature birth, perinatal asphyxia and intrauterine growth restriction can cause death or permanent disabilities like cerebral palsy,” Prof Hooper explained. “What is less well known is that these events can have lifelong effects, with the potential to contribute to diabetes, obesity, coronary artery disease and hypertension. “This impact on health extends from birth, through childhood and into adult life, and it can influence the health of future generations.”

26 / HUDSON INSTITUTE OF MEDICAL RESEARCH

135

RESEARCH PUBLICATIONS

PHD AND HONOURS GRADUATES

The program will look to tackle some of the most challenging problems in modern perinatal medicine, such as improving the transition to newborn life for very premature babies. Researchers will examine the babies’ crucial transition to air-breathing, a time when preterm babies and those exposed to intrauterine growth restriction, lung hypoplasia and birth asphyxia, are most at risk. They will also look at developing new techniques for detecting, preventing and treating neonatal lung disease, a relatively common but potentially fatal condition. “We will use a multidisciplinary approach to understand the science and develop and optimise new treatments for improving the health and care of infants during the perinatal period,” Prof Hooper said.

STUDENTS

100

Menstruating rodent to progress women’s health research Few mammals menstruate. This means that research into menstruation and menstrual disorders in women has been stalled by the lack of an appropriate preclinical model in which scientists can study these conditions. As a result, disorders like endometriosis and premenstrual syndrome remain poorly understood, making it difficult for researchers to progress new treatments. Researchers in Dr Hayley Dickinson’s Embryology and Placental Biology group were the first in the world to observe menstruation in a rodent called the spiny mouse (Acomys cahirinus). The team is developing ways to study the mechanisms of menstrual

STAFF

DISEASES IMPACTED BY OUR RESEARCH

shedding and repair in the spiny mouse to better understand pregnancy and menstrual conditions including endometriosis, which affects one in every ten women.

Creatine could be vital for baby growth in the womb Dr Dickinson’s team is also leading research into how a baby’s growth during pregnancy may depend on a mother’s levels of a critical nutrient called creatine. Their study, published in the British Journal of Obstetrics and Gynaecology, demonstrated links between a mother’s creatine levels during pregnancy and the size of her baby at birth. The finding has prompted a worldfirst study of 900 pregnant women at Monash Health to determine optimum creatine levels during pregnancy.

2016 ANNUAL REPORT / 27

Dr Dickinson said the discovery is a major breakthrough for understanding the importance of maternal diet and its impact on an unborn baby’s growth.

Research group heads

New research collaboration announced

Dr Hayley Dickinson (Embryology and Placental Biology)

A new research collaboration between Hudson Institute of Medical Research, Monash University and Swiss-based healthcare company Roche will aim to develop next-generation treatments for autoimmune diseases, focused on proteins targeting novel molecular pathways.

A/Prof Caroline Gargett (Endometrial Stem Cells)

The partnership, announced in late 2016, will enable the multidisciplinary research team and Roche to work together to advance and translate existing and new intellectual property into novel treatments.

A/Prof Tim Moss (Perinatal Inflammation)

The collaboration has arisen from work performed by Associate Professor Marcel Nold and Dr Claudia Nold (National Heart Foundation of Australia Future Leader Fellow) from Hudson Institute and Monash University’s Department of Paediatrics, and Professor James Whisstock and Dr Andrew Ellisdon from the Monash Biomedicine Discovery Institute.

Prof Stuart Hooper (Fetal and Neonatal Health) A/Prof Jim Buttery (Infant and Child Health)

Prof Rosemary Horne (Infant and Child Health) Prof Graham Jenkin (Cell Therapy and Regenerative Medicine) Dr Rebecca Lim (Amnion Cell Biology)

A/Prof Marcel Nold and Dr Claudia Nold (Interventional Immunology in Neonatal Diseases) Dr Graeme Polglase (Perinatal Transition) A/Prof David Walker (Fetal and Neonatal Health Neurodevelopment) Dr Megan Wallace (Lung Development) A/Prof Flora Wong (Neonatal Brain Protection) Prof Nick Freezer, Head, Department of Paediatrics, School of Clinical Sciences at Monash University

A/Prof Suzanne Miller, Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash University (Neurodevelopment and Neuroprotection) Prof Euan Wallace, Head, Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash University (Maternal and Perinatal Medicine)

Our supporters Cerebral Palsy Alliance Children’s Cancer Foundation Ferring Pharmaceuticals Fielding Foundation Ian Potter Foundation Inner Wheel Australia Monash Institute of Medical Engineering NHMRC Perpetual Trustees The Rebecca L. Cooper Medical Research Foundation

28 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS COMMON COLD, VIRAL INFECTION, ANTIBIOTIC RESISTANCE ]

2016 ANNUAL REPORT / 29

CENTRE FOR INNATE IMMUNITY AND INFECTIOUS DISEASES (CiiiD)

WWI antiseptic could be key to fighting 21st century viral infections A topical antiseptic derived from coal tar and used to treat wounds and ‘sleeping sickness’ in soldiers during WWI could activate the immune system to protect against viral infection, and may prove key in the fight against antibiotic resistance, CiiiD researchers have shown.

The discovery, led by Dr Michael Gantier and Dr Geneviève Pépin, and published in the journal Nucleic Acids Research, revealed that the century-old antiseptic ‘acriflavine’ was protective against the common cold virus (rhinovirus). The team believes the way in which acriflavine activates the immune system may also offer a useful tool in the fight against viral pandemics and could have the potential to combat superbug resistance.

Whole picture revealed Dr Gantier, Head of the Nucleic Acids and Innate Immunity research group, said acriflavine was used to treat everything from gonorrhoea to urinary infections prior to WWII, but a whole picture of its mechanism of action has evaded scientists until now. The researchers pretreated human lung cells with acriflavine before introducing rhinovirus infection, and found that acriflavine protected the cells against infection by triggering an antiviral immune response. “Acriflavine was heavily used during WWI as a topical antiseptic to treat

wounds. Early scientific literature describes its antibacterial qualities in test tubes, but its very effective action on the skin has never been fully defined or explored,” Dr Gantier said. “We have shown for the first time that acriflavine works by binding to cellular DNA and activating the host immune system, unleashing a powerful immune response on a potentially broad range of pathogens. “The effect is twofold; acriflavine directly affects the replication of the pathogen and then the activation of the host immune system steps in, which helps to clear the infection,” he explained.

ACRIFLAVINE FACTS Acriflavine (also known as trypaflavine) was first identified as an antiseptic by German scientists in 1912. It was used by soldiers during WWI to treat wounds and kill the parasites that caused ‘sleeping sickness’. Australia’s volunteer nurses in WWII also carried acriflavine in their kits.

30 / HUDSON INSTITUTE OF MEDICAL RESEARCH

War on superbugs Dr Pépin, first author on the paper, says acriflavine could one day offer a safeguard against antibioticresistant bacteria or could be used during a viral outbreak to trigger a baseline immune response to an infection, such as SARS or influenza, in at-risk groups. “Acriflavine was used in the first half of the twentieth century as a topical antibacterial, before being supplanted by penicillin. Now, antibiotic-resistant superbugs are a growing threat to human health,” Dr Pépin said.

“Our study indicates that acriflavine stimulates the host immune system, rather than simply just killing bacteria, suggesting it wouldn’t be as likely to drive mutations in bacteria. This shows a safeguard against resistance and a potential alternative to current antibacterial drugs.” Next, the team will use preclinical models to test how well acriflavine mobilises the immune system against more virulent pathogens.

Collaborating organisations Monash Lung and Sleep at Monash Medical Centre; The ACRF Chemical Biology Division at The Walter and Eliza Hall Institute of Medical Research

Funding partners NHMRC; ARC

More information Pépin G, Nejad C, Thomas BJ, Ferrand J, McArthur K, Bardin PG, Williams BR and Gantier MP (2016) Activation of cGAS-dependent antiviral responses by DNA intercalating agents. Nucleic Acids Res. DOI:10.1093/nar/gkw878

2016 ANNUAL REPORT / 31

Acriflavine stimulates the host immune system, rather than simply just killing bacteria, suggesting it wouldn’t be as likely to drive mutations in bacteria.

Team Dr Geneviève Pépin, Miss Charlotte Nejad, Dr Jonathan Ferrand, Dr Belinda Thomas, Prof Philip Bardin, Prof Bryan Williams, Dr Michael Gantier

32 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS LUNG CANCER, EMPHYSEMA ]

2016 ANNUAL REPORT / 33

CENTRE FOR INNATE IMMUNITY AND INFECTIOUS DISEASES (CiiiD)

Breakthrough for lung cancer and emphysema offers hope to patients Lung cancer and emphysema combined claim the lives of about 15 000 Australians each year. These lung diseases could soon be diagnosed much earlier and targeted with an existing drug, which could vastly improve patient outcomes, thanks to a major discovery by our scientists.

LUNG CANCER AND EMPHYSEMA FACTS • Lung cancer is the most common cancer in the world and the leading cause of cancer death in Australia. • Emphysema is predicted by the World Health Organization to be the third-leading cause of death worldwide by 2020, behind heart disease and cancer. • Patients with emphysema are at an increased risk (between 25 and 30 per cent) of also developing lung cancer.

In two separate studies taking more than six years to complete, the CiiiD team, headed by Professor Brendan Jenkins, identified that an inflammation-causing molecule, interleukin 6 (IL-6), propels emphysema and lung cancer through a process called trans-signalling. The researchers found receptors essential for the IL-6 trans-signalling process are present in high levels in the blood of both emphysema and lung cancer patients, giving both diseases the same unique signature

that can be used for early disease detection. In a double hit, the researchers also discovered that an experimental drug called sgp130Fc has the ability to halt the progression of both diseases. This drug, developed by the team’s German collaborator Professor Stefan Rose-John at the University of Kiel, is already in a clinical trial for inflammatory bowel disease.

Expect the unexpected “The results were surprising because lung cancer and emphysema are polar opposites. Emphysema is characterised by the loss of lung tissue and lung cancer by the uncontrolled growth of tissue,” said Prof Jenkins. “Trans-signalling and IL-6 are having very important effects on lung disease—they are master regulators and can both be targeted with sgp130Fc.”

Early detection, saving lives “We are now working with our clinical collaborators at Monash Health, led

34 / HUDSON INSTITUTE OF MEDICAL RESEARCH

by Professor Philip Bardin, to analyse blood samples from lung cancer and emphysema patients to develop a simple blood test that could be used to detect both diseases,” Prof Jenkins said. Early detection for both lung cancer and emphysema is difficult, meaning mortality rates are high. Many patients present with the diseases at a late stage, so treatment options are limited. For example, emphysema can currently only be diagnosed in later stages by a CT scan. “Early detection is crucial to effective management and treatment of both diseases. A blood test has the potential to vastly improve survival rates through earlier diagnosis, while sgp130Fc has the ability to halt the progression of lung cancer and emphysema,” said Prof Jenkins.

Next steps Prof Jenkins is cautiously optimistic about the drug’s potential. Armed with both findings, his team will now investigate potential uses for

sgp130Fc in managing lung cancer and emphysema. “Not every patient with emphysema or lung cancer is a candidate for this drug, but with clinical trials we can identify which patients would respond to treatment and at which stage of the disease. We believe there’s a real opportunity here to target and treat patients with these lung diseases.” The study on emphysema, a culmination of six years’ work for the team, including first author and NHMRC Biomedical Fellow, Dr Saleela Ruwanpura, was published in the American Journal of Respiratory and Critical Care Medicine. It follows on from a related study on lung cancer by the team, including first author and PhD student Gavin Brooks, which was published in the top-ranked Cancer Research journal.

Collaborating organisations Monash Health; University of Kiel, Germany; NovImmune

SA, Switzerland; University of Melbourne; RMIT University

Funding partners NHMRC; The Sylvia and Charles Viertel Charitable Foundation

More information Ruwanpura SM, McLeod L, Dousha LF, Seow HJ, Alhayyani S, Tate MD, Deswaerte V, Brooks GD, Bozinovski S, MacDonald M, Garbers C, King PT, Bardin PG, Vlahos R, Rose-John S, Anderson GP and Jenkins BJ (2016) Therapeutic targeting of the IL-6 trans-signalling/mTORC1 axis in pulmonary emphysema. Am J Respir Crit Care Med 194:1494-1505. Brooks GD, McLeod L, Alhayyani S, Miller A, Russell PA, Ferlin W, RoseJohn S, Ruwanpura S and Jenkins BJ (2016) IL6 Trans-signaling promotes KRAS-driven lung carcinogenesis. Cancer Res 76:866-876.

2016 ANNUAL REPORT / 35

In a double hit, the researchers also discovered that an experimental drug called sgp130Fc has the ability to halt the progression of both diseases.

Teams Lung cancer: Mr Gavin Brooks, Ms Louise McLeod, Mr Sultan Alhayyani, Dr Alistair Miller, Dr Saleela Ruwanpura, Prof Brendan Jenkins Emphysema: Dr Saleela Ruwanpura, Ms Louise McLeod, Mr Sultan Alhayyani, Dr Michelle Tate, Dr Virginie Deswaerte, Mr Gavin Brooks, Dr Martin MacDonald, Dr Paul King, Prof Philip Bardin, Prof Brendan Jenkins

36 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS CHILDHOOD BRAIN CANCER, MEDULLOBLASTOMA ]

2016 ANNUAL REPORT / 37

CENTRE FOR CANCER RESEARCH (CCR)

Australian-first service to help children with brain tumours Children with the most common type of brain cancer could be spared unnecessary radiation and chemotherapy, thanks to a breakthrough new program from the Centre for Cancer Research.

Our researchers are establishing a pilot for an Australian-first service that will significantly reduce the time it takes for children with the most common type of solid brain tumour, medulloblastoma, to receive a prognosis. This more efficient service will help doctors to formulate the best treatment plan with the least side effects for these children.

MEDULLOBLASTOMA FACTS • Medulloblastoma represents 20 per cent of all childhood brain cancers. • There are four subgroups of medulloblastoma, each with different causes, requiring different treatments.

Tumour samples from Australia are currently sent overseas for analysis, a process that can take up to two months. This new service, a collaboration between Hudson Institute of Medical Research, Monash Health and the Monash Children’s Hospital Cancer Centre, will provide the same prognostic information within three weeks.

“We are excited to be the first Australian laboratory to provide a validated local service, according to international standards,” said Dr Jason Cain, who is Head of the Developmental and Cancer Biology research group within the Centre for Cancer Research at Hudson Institute. “Our service will enable doctors to provide a prognosis more quickly and to tailor cancer treatments to fit the tumour profile with the best result for the child.” This collaborative project is generously funded by the Australian Lions Childhood Cancer Research Foundation, Children’s Cancer Foundation, Robert Connor Dawes Foundation and Bailey’s Day.

New level of personalised treatment There are four subgroups of medulloblastoma and all are currently treated the same way, with chemotherapy and, where it is required, radiation. While the survival rate is around 80 per cent for average risk patients,

38 / HUDSON INSTITUTE OF MEDICAL RESEARCH

the one-size-fits-all treatment regime for this disease means children can suffer permanent and debilitating side effects like intellectual disability and issues with growth, speech and hearing loss. Emerging research suggests there are variations within the existing tumour subgroups for medulloblastoma that require further subclassification. As well as providing prognostic information to existing patients, the research team will also look to improve care for future patients. The researchers will analyse tumour samples from archived tissue banks across Australia to uncover key genetic and epigenetic differences that will inform new treatments that can be targeted to the profile of a patient’s tumour—an approach known as precision medicine. “It’s become clear over the last five years that medulloblastoma is not a single disease, but comprised of at least these four distinct subgroups, each with different causes and prognosis,” Dr Cain said. “There is a low-risk group that doesn’t need the same amount of chemotherapy or radiation. There are also targeted therapies in clinical trials showing some promising results, but they are only effective

in one high-risk subgroup. This is crucial information for these patients. “Identifying key methylation differences will enable our team to catalogue medulloblastoma treatments to each tumour subgroup, minimising unnecessary toxic treatments and lifelong side effects,” Dr Cain said. The team believes methylation array technology is also key to analysing other types of solid brain tumours, and may become the ‘gold standard’ across all extracranial solid tumours.

What is precision cancer medicine? Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in genome sequence and other unique personalised information (such as microbiome composition, health history, lifestyle and diet) to identify and deliver the right treatment to the right patient at the right time. The use of precision medicine has the potential to revolutionise healthcare delivery by improving treatment effectiveness, as well as sparing patients the costs and side effects of therapies from which they

would not benefit, based on their individualised makeup. Unlike traditional one-size-fits-all medicine, precision cancer medicine involves testing DNA from patients’ tumours to identify the mutations or other changes that drive their cancer. Scientists and physicians then use this information to identify small molecule drugs, monoclonal antibodies and other therapies that are precisely targeted for the individual patient. While such therapies are not widespread yet, there is a general consensus among cancer specialists globally that precision medicine will be central to the future of cancer care in improving treatment success rates and reducing side effects.

Collaborating organisations Monash Children's Hospital; Royal Children's Hospital

Funding partners Australian Lions Childhood Cancer Research Foundation; Robert Connor Dawes Foundation; Bailey's Day; Children's Cancer Foundation

2016 ANNUAL REPORT / 39

Identifying key methylation differences will enable our team to catalogue medulloblastoma treatments to each tumour subgroup.

Team A/Prof Elizabeth Algar, Dr Sara Khan, Dr Jason Cain, Dr Peter Downie

40 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS ADVANCED BLADDER CANCER ]

2016 ANNUAL REPORT / 41

CENTRE FOR CANCER RESEARCH (CCR)

Hope for bladder cancer patients A crucial genetic marker that heralds better treatment and outcomes for advanced bladder cancer patients has been discovered by Centre for Cancer Research scientists. The finding, published in the journal Molecular Cancer Therapeutics, represents major progress in treatment for advanced bladder cancer patients.

BLADDER CANCER FACTS • Each year, more than 2800 Australians are diagnosed with bladder cancer. • It is the fourth most common cancer among men and the ninth most common cancer among women. • Because of high rates of recurrence and continuing invasive monitoring, bladder cancer also has the highest lifetime treatment costs per patient of all cancers. • Treatments for advanced bladder cancer are currently limited to surgery and chemotherapy. In recurrent cancers, larger doses of chemotherapy are required and these drugs become less effective as the cancer progresses.

Solving a vital piece of the puzzle Researchers Dr Dhanya Sooraj, Professor Bryan Williams, Dr Dakang Xu and Dr Jason Cain were investigating why the crucial tumour

suppressor, ATF3, disappears as bladder cancer progresses. Disappearance of ATF3 correlates with poor survival rates. The team discovered that an enzyme inhibitor drug ‘pracinostat’, currently in clinical trials for other types of cancer, could be used to reactivate the ATF3 gene in bladder cancer cells, restoring cells to their original non-tumour state. Significantly, they found that once the ATF3 gene was reactivated, tumour sizes reduced, resulting in an improved chance of survival. “ATF3 is a vital piece of the puzzle in creating the best possible outcomes for advanced bladder cancer patients,” Prof Williams said. “Our results show that a normal functioning ATF3 gene is necessary for standard treatment to be effective. This gene could also be used as a biomarker for monitoring patients’ response to treatment. For example, if levels of ATF3 increase, then we may know the treatment is working.” Prof Williams added that when used in combination with chemotherapy,

42 / HUDSON INSTITUTE OF MEDICAL RESEARCH

pracinostat has the potential to be an effective new treatment approach for the majority of patients.

chemotherapy and emerging immunotherapies to improve treatment responses.

“By using a more efficient dose of chemotherapy to tackle the tumour, we could ultimately improve patients’ responses to treatment, which in turn improves survival rates and quality of life.”

The drug is already in phase II clinical trials for acute myeloid leukaemia and myelofibrosis, with promising results.

Next steps Work in preclinical models will confirm whether pracinostat can be used in combination with

The team believes the findings of this study could also be used to improve treatment options for colorectal cancer, a disease in which the expression of the ATF3 gene is also lost.

Collaborating organisation MEI Pharma

Funding partner NHMRC

More information Sooraj D, Xu D, Cain JE, Gold DP and Williams BRG (2016) Activating transcription factor 3 expression as a marker of response to the histone deacetylase inhibitor pracinostat. Mol Cancer Ther 15:1726-1739.

2016 ANNUAL REPORT / 43

ATF3 is a vital piece of the puzzle in creating the best possible outcomes for advanced bladder cancer patients.

Team Dr Dhanya Sooraj, Dr Dakang Xu, Dr Jason Cain, Prof Bryan Williams

44 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS PELVIC ORGAN PROLAPSE ]

Stem cell based pelvic organ prolapse contruct.

2016 ANNUAL REPORT / 45

THE RITCHIE CENTRE (TRC)

World first–a way forward for a hidden condition The impact of birth leaves one in four women with a lifelong hidden medical condition, but help is on the way thanks to research taking place at The Ritchie Centre.

Pelvic organ prolapse (POP) occurs when the tissues, pelvic floor muscles and ligaments that support the pelvic organs (bladder, uterus and bowel) are damaged, usually in childbirth, causing the organs to herniate or shift.

Associate Professor Caroline Gargett’s research group in The Ritchie Centre have discovered a way to extract and purify stem cells taken from the human endometrium, which could be used to help women with POP.

POP causes debilitating symptoms, including poor bladder or bowel control and pain during sex.

“Our world-first discovery means that one day we could take stem cells from the lining of a woman’s uterus to help repair some of the lifelong damage caused by childbirth,” A/Prof Gargett said.

PELVIC ORGAN PROLAPSE FACTS One in four women are affected by POP. In postmenopausal women who have had children, this figure increases to one in two. • Every year in Australia around 22 000 women undergo surgery for POP. • Around one in five women with POP will require surgical intervention. A third of these will require multiple operations. • About half of all women who have had a child have some level of prolapse, but only one in five women seek medical help.

Progressing help for women The team are working on combining the stem cells with a specially engineered mesh that mimics the delicate tissues in the vaginal walls. Around one in five women with POP will require surgical intervention. Current surgeries may involve vaginal insertion of a synthetic mesh to give the pelvic organs permanent support, but this surgery has significant side effects for around one in ten women. Some women’s bodies reject the meshes, leading to internal scarring or exposure of the mesh, requiring more surgeries to then remove them.

46 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Work in preclinical models indicates that supplementing new biocompatible meshes with endometrial stem cells may improve the outcomes of surgery. “The stem cells help the body accept new biocompatible meshes as native rather than foreign. They modify the body’s immune response to one of wound healing, rather than of scarring,” explains A/Prof Gargett. The team are also working towards production of endometrial stem cells for use in clinical trials.

“As these stem cells can be extracted in a consulting room environment, without the use of anaesthetic, they represent an attractive and accessible option for development of cell-based therapies,” A/Prof Gargett said. “We believe the endometrium may be a superior source of stem cells that could be used in many health conditions.”

Collaborating organisations CSIRO; Monash Health

Funding partner NHMRC

More information Darzi S, Werkmeister JA, Deane JA and Gargett CE (2016) Identification and characterization of human endometrial mesenchymal stem/ stromal cells and their potential for cellular therapy. Stem Cells Transl Med 5:1127-1132.

2016 ANNUAL REPORT / 47

One day we could take stem cells from the lining of a womanâ&#x20AC;&#x2122;s uterus to help repair some of the lifelong damage caused by childbirth.

Team A/Prof Caroline Gargett, Dr James Deane, Ms Saeedah Darzi

48 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS PELVIC ORGAN PROLAPSE ]

2016 ANNUAL REPORT / 49

CENTRE FOR REPRODUCTIVE HEALTH (CRH)

Non-invasive swab test for endometrial cancer Endometrial cancer is one of the most common types of cancer affecting postmenopausal women. In 2016, the disease claimed the lives of an estimated 441 women in Australia.

In a world-first finding, scientists from the Centre for Reproductive Health, led by Associate Professor Guiying Nie, discovered that the proprotein convertase (PC) enzyme activity could be the key to an early detection swab test for endometrial cancer.

ENDOMETRIAL CANCER FACTS • In 2013, there were 424 deaths from uterine cancer in Australia. In 2016, it was estimated that this will have increased to 441 deaths. • Uterine cancer is the sixth most commonly diagnosed cancer among females in Australia and the most commonly diagnosed gynaecological cancer. • Incidences are increasing in premenopausal women.

A/Prof Nie’s team found that PC activity is present in elevated levels in endocervical swabs taken from endometrial cancer patients, a finding that could inform a simple

but life-saving and non-invasive early detection swab test for endometrial cancer. “Early and non-invasive detection of endometrial cancer is critically important but currently not available,” A/Prof Nie explained. “Endometrial cancer is currently only diagnosed by a combination of different tests, which may include an ultrasound, endometrial biopsy, hysteroscopy or MRI scan. “Vaginal bleeding in postmenopausal women is an indicator that the cancer has already progressed. “A swab test is a simple and noninvasive method that could easily be performed during a woman’s regular check-up.” Previous work by A/Prof Nie’s laboratory also demonstrated that PC activity is significantly elevated in the uterine fluid of postmenopausal women with endometrial cancer. Her team will now look to further develop the two findings into a simple screening tool for endometrial cancer.

50 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Collaborating organisations

More information

Department of Obstetrics and Gynaecology; Monash University and Epworth Research Institute; Epworth HealthCare

Heng S, Stephens AN, Jobling TW and Nie G (2016) Measuring PC activity in endocervical swab may provide a simple and non-invasive method to detect endometrial cancer in post-menopausal women. Oncotarget 7:46573-46578.

Funding partners NHMRC; The CASS Foundation

2016 ANNUAL REPORT / 51

PC activity is present in elevated levels in endocervical swabs taken from endometrial cancer patients, a finding that could inform a simple but lifesaving and non-invasive early detection swab test for endometrial cancer.

Team A/Prof Guiying Nie, Ms Sophea Heng, Dr Andrew Stephens

52 / HUDSON INSTITUTE OF MEDICAL RESEARCH

[ DISCOVERY IMPACTS IVF, FERTILITY, GENETIC DISORDERS, BIRTHS ]

2016 ANNUAL REPORT / 53

CENTRE FOR GENETIC DISEASES (CGD)

Findings may help women struggling with fertility Women undergoing IVF may soon have a greater chance of achieving a pregnancy, thanks to research from our Centre for Genetic Diseases.

The study, published in the journal Scientific Reports and led by Centre Head, Professor Jus St. John, showed that improving egg quality during fertilisation resulted in an increased chance of fertilisation and development of a healthy embryo. Prof St. John’s discovery revealed that boosting the health of a woman’s egg using genetically identical mitochondrial DNA from another of her eggs improved the chance of a healthy embryo developing. Mitochondrial DNA provides key components for the mitochondria, which are like batteries that supply a cell with energy. Low counts of mitochondrial DNA within an egg are an indicator of poor function, meaning fertilisation is more likely to fail.

IVF and mitochondrial DNA facts There is no definitive data on mitochondrial DNA deficiency for women going through IVF. However, the team estimate that around 10 per cent of IVF cycles fail because of mitochondrial DNA deficiency, which equates to 16.2 per cent of cycles for women over the age of 35 years.

A ‘bigger role’ for mitochondrial DNA in pregnancy “It’s becoming clear that mitochondrial DNA has a bigger role to play in fertilisation outcome and embryo development than previously thought. “Failure to have enough mitochondrial DNA can result in fertilisation failure, embryo arrest and other genetic disorders,” said Prof St. John. Using preclinical models, Prof St. John’s team took a female’s eggs that had a low level of mitochondrial DNA, and increased the level by supplementing using mitochondrial DNA with genetically identical information, taken from another of her eggs. When this supplementation process was carried out at the same time as fertilisation of the egg with sperm, the result was the development of a healthy embryo.

What’s a healthy egg? A healthy egg normally contains more than 150 000 copies of

54 / HUDSON INSTITUTE OF MEDICAL RESEARCH

mitochondrial DNA, which help an egg to develop during and after fertilisation. Some women undergoing IVF have low levels of mitochondrial DNA in their eggs (fewer than 50 000 copies), which often results in these eggs failing to either fertilise or to develop into embryos.

“Previously, scientists had not realised just how important mitochondrial DNA is to the processes of fertilisation and development. Our results show that it is the amount of mitochondrial DNA that is important for development,” Prof St. John said.

While it was known that other factors including a woman’s age, environment (such as exposure to toxins or smoking) and medical issues can affect egg health, Prof St. John’s world-first discovery adds another factor to this list.

Collaborating organisations Monash University; Harvard University, USA; University of New South Wales

Funding partner OvaScience Inc, USA

More information Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA and St John JC (2016) Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep 6:23229.

2016 ANNUAL REPORT / 55

Boosting the health of a womanâ&#x20AC;&#x2122;s egg using genetically identical mitochondrial DNA from another of her eggs improved the chance of a healthy embryo developing.

Team Dr Gael Cagnone, Ms Te-Sha Tsai, Dr Yogeshwar Makanji, Ms Pamela Matthews, Ms Jodee Gould, Dr Kirstin Elgass, Dr Matthew McKenzie, Prof Jus St. John

56 / HUDSON INSTITUTE OF MEDICAL RESEARCH

2016 publications BOOKS 1 McKenzie M (2016) Mitochondrial DNA: Methods and Protocols. (ed McKenzie M). Methods in Molecular Biology. New York: Springer, pp 1-234.

Horne R (2016) Sleep disorders in newborns and infants. In Sleep Disorders in Children. Nevšímalová S and Bruni O, eds. Switzerland: Springer. pp 129-153.

Lyons VG and McCoy CE (2016) Simple methods to investigate microRNA induction in response to toll-like receptors. In Toll-Like Receptors, 2nd Edn. McCoy CE, ed. Methods in Molecular Biology. New York: Springer. Vol 1390, pp 159-182.

Markman B, Serra V and Tabernero J (2016) mTOR inhibition beyond rapalogs. In mTOR Inhibition for Cancer Therapy: Past, Present and Future Mita M, Rowinsky EK and Mita A, eds. France: Springer-Verlag. pp 251-275.

Ahmed N, Greening D, Samardzija C, Escalona RM, Chen M, Findlay JK and Kannourakis G (2016) Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells. Sci Rep 6:30061.

Praszkier J, Sutton P and Ferrero RL (2016) Virulence mechanisms of Helicobacter Pylori: An Overview. In Helicobacter Pylori Research. Backert S and Yamaoka Y, eds. Japan: Springer. pp 57-87.

Sun X, Lee W, Vaghjiani V and St John J (2016) Analysis of mitochondrial DNA copy number and its regulation through DNA methylation of POLGA. In Mitochondrial DNA, 3rd Edn. McKenzie M, ed. Methods in Molecular Biology New York: Springer. Vol 1351, pp 131-141.

Alankarage D, Lavery R, Svingen T, Kelly S, Ludbrook L, Bagheri-Fam S, Koopman P and Harley V (2016) SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5) during mammalian sex development. Int J Biochem Cell Biol 79:41-51.

Alexiadis M, Chu S, Leung DT, Gould J, Jobling T and Fuller PJ (2016) Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors. Oncotarget 7:14207-14219.

Allison BJ, Hooper SB, Coia E, Zahra VA, Jenkin G, Malhotra A, Sehgal A, Kluckow M, Gill AW, Sozo F, Miller SL and Polglase GR (2016) Ventilation induced lung injury is not exacerbated by growth restriction in preterm lambs. Am J Physiol Lung Cell Mol Physiol 310:213-223.

Andraweera PH, Bobek G, Bowen C, Burton GJ, Correa Frigerio P, Chaparro A, Dickinson H, Duncombe G, Hyett J, Illanes SE, Johnstone E, Kumar S, Morgan TK, Myers J, Orefice R, Roberts CT, Salafia CM, Thornburg KL, Whitehead CL and Bainbridge SA (2016) IFPA meeting 2015 workshop report: Mechanistic role of the placenta in fetal programming; biomarkers of placental function and complications of pregnancy; late onset fetal growth restriction surveillance and monitoring. Placenta 48: 7-11.

BOOK CHAPTERS 1

Allan C and McLachlan R (2016) Androgen deficiency disorders. In Endocrinology: Adult and Pediatric 7th Edn. De Groot L et al., eds. Philadelphia, PA: Elsevier. Vol 2, pp 2394-2420. Atik A, Harding R, De Matteo R and Tolcos M (2016) Caffeine and the developing brain: molecular and cellular effects. In Neuropathology of Drug Addictions and Substance Misuse. Preedy VR, ed. USA: Elsevier. Vol 3, pp 753-761. Cagnone G, Vaghjiani V, Lee W, Sun C, Johnson J, Yeung KY and St John JC (2016) Analysis of the mitochondrial DNA and its replicative capacity in induced pluripotent stem cells. In Induced Pluripotent Stem (iPS) Cells. Turksen K and Nagy A, eds. Methods in Molecular Biology. New York: Springer. Vol 1357, pp 231-267. Chen JL, Colgan TD, Walton KL, Gregorevic P and Harrison CA (2016) The TGF-beta signalling network in muscle development, adaptation and disease. In Growth Factors and Cytokines in Skeletal Muscle Development, Growth, Regeneration and Disease. White J and Smythe G, eds. Advances in Experimental Medicine and Biology Switzerland: Springer. Vol 900, pp 97-131. Dhagat U, Nero TL, Kan WL, Hercus TR, Broughton SE, De Weerd N, Jenkins B, Mansell A, Guthridge MA, Hertzog P, Lopez A and Parker MW (2016) Cytokine receptors and their ligands. In Encylopedia of Cell Biology. Bradshaw RA and Stahl PD, eds. Cell Communication. USA: Academic Press. Vol 3, pp 22-36. Dowling JK and Dellacasagrande J (2016) Toll-Like receptors: ligands, cell-based models, and readouts for receptor action. In Toll-Like Receptors, 2nd Edn. McCoy CE, ed. Methods in Molecular Biology. New York: Springer. Vol 1390, pp 3-27. Edgell TJ, Evans J, Rombaults LJR, Vollenhoven B and Salamonsen L (2016) Assessing receptivity of the human endometrium to improve outcomes of fertility treatment. In Uterine Endometrial Function. Kanzaki H, ed. Japan: Springer. pp 27-28. Ferrand J and Gantier MP (2016) Assessing the inhibitory activity of oligonucleotides on TLR7 sensing. In TollLike Receptors 2nd Edn. Mc Coy CE, ed. Methods in Molecular Biology. New York: Springer. Vol 1390, pp 79-90. Hertzog P, Bourke NM, de Weerd NA and Mangan NE (2016) New interferons. In Encyclopedia of Immunobiology. Ratcliffe MJ, ed. USA: Elsevier. Vol 1, pp 501-508.

JOURNAL ARTICLES 1 Abumaree MH, Almutairi A, Cash S, Boeuf P, Chamley LW, Gamage T, James JL, Kalionis B, Khong TY, Kolahi KS, Lim R, Liong S, Morgan TK, Motomura K, Peiris HN, Pelekanos RA, Pelzer E, Shafiee A, Lash GE and Natale D (2016) IFPA meeting 2015 workshop report IV: Placenta and obesity; stem cells of the feto-maternal interface; placental immunobiology and infection. Placenta 48:17-20.

Te Pas AB and Hooper SB (2016) Initiation of breathing at birth. In Fetal and Neonatal Lung Development. Jobe AH, Whitsett J and Abman S, eds. USA: Cambridge University Press. pp 164-170.

Trounce IA, Ackerley J and McKenzie M (2016) Generation of xenomitochondrial embryonic stem cells for the production of live xenomitochondrial mice. In Mitochondrial DNA, 3rd Edn. McKenzie M, ed. Methods in Molecular Biology. Springer. Vol 1351, pp 163-173.

Wallace MJ, Harding R and Hooper SB (2016) Physiologic mechanisms of normal and altered lung growth before and after birth In Fetal and Neonatal Physiology, 5th Edn. Polin R, Abman S, Benitz B and Rowitch D, eds. London: Elsevier Academic Press. Vol 2, pp 646-657.

West AC and Jenkins BJ (2016) Investigating the role of toll-like receptors in mouse models of gastric cancer. In TollLike Receptors, 2nd Edn. McCoy CE, ed. Methods in Molecular Biology. New York: Springer. Vol 1390, pp 427-449.

Antony N, McDougall AR, Mantamadiotis T, Cole TJ and Bird AD (2016) Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms. Sci Rep 6:25569.

Wong F (2016) Cerebral blood flow measurements in the neonatal brain. In Prenatal and Postnatal Determinants of Development. Walker D, ed. Humana Press. Vol 9, pp 69-87.

Arachchi S, Armstrong DS, Roberts N, Baxter M, McLeod S, Davey MJ and Nixon GM (2016) Clinical outcomes in a high nursing ratio ward setting for children with obstructive sleep apnea at high risk after adenotonsillectomy. Int J Pediatr Otorhinolaryngol 82:54-57.

Aridas JD, McDonald CA, Paton MC, Yawno T, Sutherland AE, Nitsos I, Pham Y, Ditchfield M, Fahey MC, Wong F, Malhotra A, Castillo-Melendez M, Bhakoo K, Wallace EM, Jenkin G and Miller SL (2016) Cord blood mononuclear cells prevent neuronal

20 Wu D and Gantier MP (2016) Normalization of affymetrix miRNA microarrays for the analysis of cancer samples. In Microarray Data Analysis, 2nd Edn. Guzzi PH, ed. Methods in Molecular Biology. Humana Press. Vol 1375, pp 1-10.

2016 ANNUAL REPORT / 57

apoptosis in response to perinatal asphyxia in the newborn lamb. J Physiol 594:1421-1435. 10

Ataman LM, Rodrigues JK, Marinho RM, Caetano JP, Chehin MB, Alves da Motta EL, Serafini P, Suzuki N, Furui T, Takae S, Sugishita Y, Morishige KI, Almeida-Santos T, Melo C, Buzaglo K, Irwin K, Wallace WH, Anderson RA, Mitchell RT, Telfer EE, Adiga SK, Anazodo A, Stern C, Sullivan E, Jayasinghe Y, Orme L, Cohn R, McLachlan R, Deans R, Agresta F, Gerstl B, Ledger WL, Robker RL, de Meneses ESJM, Silva LH, Lunardi FO, Lee JR, Suh CS, De Vos M, Van Moer E, Stoop D, Vloeberghs V, Smitz J, Tournaye H, Wildt L, Winkler-Crepaz K, Andersen CY, Smith BM, Smith K and Woodruff TK (2016) Creating a global community of practice for oncofertility. J Glob Oncol 2:83-96. Bardin PG, Low K and Ruane LE (2016) Vocal cord dysfunction: asking the right questions. Clin Exp Allergy 45:1374-1375. Barton SK, McDougall AR, Melville JM, Moss TJ, Zahra VA, Lim T, Crossley KJ, Polglase GR and Tolcos M (2016) Differential short-term regional effects of early high dose erythropoietin on white matter in preterm lambs after mechanical ventilation. J Physiol 594:1437-1449. Barton SK, Tolcos M, Miller SL, ChristophRoehr C, Schmolzer GM, Moss TJ, Hooper SB, Wallace EM and Polglase GR (2016) Ventilation-induced brain injury in preterm neonates: a review of potential therapies. Neonatology 110:155-162. Behre HM, Zitzmann M, Anderson RA, Handelsman DJ, Lestari SW, McLachlan RI, Meriggiola MC, Misro MM, Noe G, Wu FC, Festin MP, Habib NA, Vogelsong KM, Callahan MM, Linton KA and Colvard DS (2016) Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab 101:47794788.

Blake J, Hu D, Cain JE and Rosenblum ND (2016) Urogenital development in Pallister-Hall syndrome is disrupted in a cell lineage-specific manner by constitutive expression of GLI3 repressor. Hum Mol Genet 25:437-447.

Blank DA, Hooper SB, Binder-Heschl C, Kluckow M, Gill AW, LaRosa DA, Inocencio IM, Moxham A, Rodgers K, Zahra VA, Davis PG and Polglase GR (2016) Lung ultrasound accurately detects pneumothorax in a preterm newborn lamb model. J Paediatr Child Health 52:643648.

23 Brew N, Azhan A, den Heijer I, Boomgardt M, Davies GI, Nitsos I, Miller SL, Walker AM, Walker DW and Wong FY (2016) Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain. Neuroscience 316:82-93. 24 Brooks GD, McLeod L, Alhayyani S, Miller A, Russell PA, Ferlin W, Rose-John S, Ruwanpura S and Jenkins BJ (2016) IL6 Trans-signaling promotes KRAS-driven lung carcinogenesis. Cancer Res 76:866876. 25 Brosens I, Gargett CE, Guo SW, Puttemans P, Gordts S, Brosens JJ and Benagiano G (2016) Origins and progression of adolescent endometriosis. Reprod Sci 23:1282-1288. 26 Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA, Stares MD, Goulding D and Lawley TD (2016) Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533:443-446.

Bennet L, Fyfe KL, Yiallourou SR, Merk H, Wong FY and Horne RS (2016) Discrimination of sleep states using continuous cerebral bedside monitoring (aEEG) compared to polysomnography in infants. Acta Paediatr 105:582-587.

Bennett GA, Palliser HK, Walker D and Hirst J (2016) Severity and timing: How prenatal stress exposure affects glial developmental, emotional behavioural and plasma neurosteroid responses in guinea pig offspring. Psychoneuroendocrinology 70:47-57.

28 Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA and St John JC (2016) Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep 6:23229.

Bielanowicz A, Johnson RW, Goh H, Moody SC, Poulton IJ, Croce N, Loveland KL, Hedger MP, Sims NA and Itman C (2016) Prepubertal di-n-butyl phthalate exposure alters Sertoli and Leydig cell function and lowers bone density in adult male mice. Endocrinology 157:2595-2603.

Biggs SN, Meltzer LJ, Tapia IE, Traylor J, Nixon GM, Horne RS, Doyle LW, Asztalos E, Mindell JA and Marcus CL (2016) Sleep/ wake patterns and parental perceptions of sleep in children born preterm. J Clin Sleep Med 12:711-717.

20 Binder-Heschl C, Urlesberger B, Schwaberger B, Koestenberger M and Pichler G (2016) Borderline hypotension: how does it influence cerebral regional tissue oxygenation in preterm infants? J Matern Fetal Neonatal Med 29:23412346.

Binder NK, Evans J, Salamonsen LA, Gardner DK, Kaitu’u-Lino TJ and Hannan NJ (2016) Placental growth factor is secreted by the human endometrium and has potential important functions during embryo development and implantation. PLoS One 11:e0163096.

Cagnone C, Tsa T-S, Srirattana K, Rossello F, Powel DR, Trounce IA, Rohrer G, Cree L and St John JC (2016) Segregation of naturally occurring mitochondrial DNA variants in a mini-pig model. Genetics 202:931-944.

29 Carroll EC, Jin L, Mori A, Munoz-Wolf N, Oleszycka E, Moran H, Mansouri SD, McEntee C, Lambe E, Agger E, Andersen P, Cunningham C, Hertzog P, Fitzgerald A, Bowie AG and Lavelle E (2016) The vaccine adjuvant chitosan promotes cellular immunity via DNA sensor cGASSTING-dependent induction of type I interferons. Immunity 44:597-608. 30 Chen JL, Walton KL, Qian H, Colgan TD, Hagg A, Watt MJ, Harrison CA and Gregorevic P (2016) Differential effects of interleukin-6 and activin A in the development of cancer-associated cachexia. Cancer Res 76:5372-5382. 31

Chen Q, Wang Y, Zhao M, Hyett J, da Silva Costa F and Nie G (2016) Serum levels of GDF15 are reduced in preeclampsia and

the reduction is more profound in lateonset than early-onset cases. Cytokine 83:226-230. 32 Cho SX, Berger PJ, Nold-Petry CA and Nold MF (2016) The immunological landscape in necrotising enterocolitis. Expert Rev Mol Med 18:e12. 33 Chonwerawong M, Ave P, Huerre M and Ferrero RL (2016) Interferon-gamma promotes gastric lymphoid follicle formation but not gastritis in Helicobacterinfected BALB/c mice. Gut Pathog 8:61. 34 Clifton VL, Moss TJ, Wooldridge AL, Gatford KL, Liravi B, Kim D, Muhlhausler BS, Morrison JL, Davies A, De Matteo R, Wallace MJ and Bischof RJ (2016) Development of an experimental model of maternal allergic asthma during pregnancy. J Physiol 594:1311-1325. 35 Cohen E, Baerts W, Alderliesten T, Derks J, Lemmers P and van Bel F (2016) Growth restriction and gender influence cerebral oxygenation in preterm neonates. Arch Dis Child Fetal Neonatal Ed 101:156-161. 36 Cohen E, Dix L, Baerts W, Alderliesten T, Lemmers P and van Bel F (2016) Reduction in cerebral oxygenation due to patent ductus arteriosus is pronounced in small-for-gestational-age neonates. Neonatology 111:126-132. 37 Cohen E, Wong FY, Horne RS and Yiallourou SR (2016) Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. Pediatr Res 79:821-830. 38 Cousins FL, Kirkwood PM, Saunders PT and Gibson DA (2016) Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling. Sci Rep 6:36748. 39 Crawshaw JR, Hooper SB, Te Pas AB, Allison BA, Wallace MJ, Kerr L, Lewis RA, Morley CJ, Leong AF and Kitchen MJ (2016) Effect of betamethasone, surfactant and positive end-expiratory pressures on lung aeration at birth in preterm rabbits. J Appl Physiol 12:750759. 40 Croft B, Ayers K, Sinclair A and Ohnesorg T (2016) Review disorders of sex development: The evolving role of genomics in diagnosis and gene discovery. Birth Defects Res C Embryo Today 108:337-350. 41

Cullen JK, Abdul Murad N, Yeo A, McKenzie M, Ward M, Chong KL, Schieber NL, Parton RG, Lim YC, Wolvetang E, Maghzal GJ, Stocker R and Lavin MF (2016) AarF domain containing kinase 3 (ADCK3) mutant cells display signs of oxidative stress, defects in mitochondrial homeostasis and lysosomal accumulation. PLoS One 11:e0148213.

42 Daly C, Ghosh P, Jenkin G, Oehme D and Goldschlager T (2016) A review of animal models of intervertebral disc degeneration: pathophysiology, regeneration, and translation to the clinic. Biomed Res Int 2016:5952165. 43 Darzi S, Urbankova I, Su K, White J, Lo C, Alexander D, Werkmeister JA, Gargett CE and Deprest J (2016) Tissue response to collagen containing polypropylene meshes in an ovine vaginal repair model. Acta Biomater 39:114-123.

58 / HUDSON INSTITUTE OF MEDICAL RESEARCH

44 Darzi S, Werkmeister JA, Deane JA and Gargett CE (2016) Identification and characterization of human endometrial mesenchymal stem/stromal cells and their potential for cellular therapy. Stem Cells Transl Med 5:1127-1132. 45 Davies PS, Funder J, Palmer DJ, Sinn J, Vickers MH, Wall CR and as the Australia New Zealand Early Life Nutrition Working Party (2016) Early life nutrition and the opportunity to influence long-term health: an Australasian perspective. J Dev Orig Health Dis 7:440-448. 46 Davies-Tuck M, Mockler JC, Stewart L, Knight M and Wallace EM (2016) Obesity and pregnancy outcomes: Do the relationships differ by maternal region of birth? A retrospective cohort study. BMC Pregnancy Childbirth 16:288. 47 de Kretser DM, Bensley JG, Phillips DJ, Levvey BJ, Snell GI, Lin E, Hedger MP and O’Hehir RE (2016) Substantial increases occur in serum activins and follistatin during lung transplantation. PLoS One 11:e0140948. 48 de Valle E, Grigoriadis G, O’Reilly LA, Willis SN, Maxwell MJ, Corcoran LM, Tsantikos E, Cornish JK, Fairfax KA, Vasanthakumar A, Febbraio MA, Hibbs ML, Pellegrini M, Banerjee A, Hodgkin PD, Kallies A, Mackay F, Strasser A, Gerondakis S and Gugasyan R (2016) NFkappaB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med 213:621-641. 49 Deane JA, Ong YR, Cain JE, Jayasekara WS, Tiwari A, Carlone DL, Watkins DN, Breault DT and Gargett CE (2016) The mouse endometrium contains epithelial, endothelial and leucocyte populations expressing the stem cell marker telomerase reverse transcriptase. Mol Hum Reprod 22:272-284. 50 Demirci EK, Salamonsen LA and Gauster M (2016) The role of CX3CL1 in fetalmaternal interaction during human gestation. Cell Adh Migr 10:189-196. 51

Dickinson H, Davies-Tuck M, Ellery SJ, Grieger JA, Wallace EM, Snow RJ, Walker DW and Clifton VL (2016) Maternal creatine in pregnancy: a retrospective cohort study. Br J Obstet Gynaecol 123:1830-1838.

52 Dickinson H, Moss TJ, Gatford KL, Moritz KM, Akison L, Fullston T, Hryciw DH, Maloney CA, Morris MJ, Wooldridge AL, Schjenken JE, Robertson SA, Waddell BJ, Mark PJ, Wyrwoll CS, Ellery SJ, Thornburg KL, Muhlhausler BS and Morrison JL (2016) A review of fundamental principles for animal models of DOHaD research: an Australian perspective. J Dev Orig Health Dis 7:449-472. 53 Dimitriadis E (2016) The use of malaria glycosaminoglycan to block cancers— lessons from the human placenta. Transl Cancer Res 5:1085-1087. 54 Dinh QN, Young MJ, Evans MA, Drummond GR, Sobey CG and Chrissobolis S (2016) Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor. Brain Res 1637:146-153. 55 Dowling JK and Mansell A (2016) Tolllike receptors: the swiss army knife of immunity and vaccine development. Clin Transl Immunology 5:e85.

56 Edwards BA, Andara C, Landry S, Sands SA, Joosten SA, Owens RL, White DP, Hamilton GS and Wellman A (2016) Upperairway collapsibility and loop gain predict the response to oral appliance therapy in obstructive sleep apnea patients. Am J Respir Crit Care Med 194:1413-1422. 57 Eggermann K, Bliek J, Brioude F, Algar E, Buiting K, Russo S, Tumer Z, Monk D, Moore G, Antoniadi T, Macdonald F, Netchine I, Lombardi P, Soellner L, Begemann M, Prawitt D, Maher ER, Mannens M, Riccio A, Weksberg R, Lapunzina P, Gronskov K, Mackay DJ and Eggermann T (2016) EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver-Russell and Beckwith-Wiedemann syndrome. Eur J Hum Genet 24:1377-1387.

63 Emmerson SJ and Gargett CE (2016) Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse. World J Stem Cells 8:202-215. 64 Evans J (2016) Hyperglycosylated hCG: a unique human implantation and invasion factor. Am J Reprod Immunol 75:333-340. 65 Evans J, Salamonsen LA, Winship A, Menkhorst E, Nie G, Gargett CE and Dimitriadis E (2016) Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol 12:654-667. 66 Fang DY, Lu B, Hayward S, de Kretser DM, Cowan PJ and Dwyer KM (2016) The role of activin A and B and the benefit of follistatin treatment in renal ischemiareperfusion injury in mice. Transplant Direct 2:e87.

58 Eggermann T, Brioude F, Russo S, Lombardi MP, Bliek J, Maher ER, Larizza L, Prawitt D, Netchine I, Gonzales M, Gronskov K, Tumer Z, Monk D, Mannens M, Chrzanowska K, Walasek MK, Begemann M, Soellner L, Eggermann K, Tenorio J, Nevado J, Moore GE, Mackay DJ, Temple K, Gillessen-Kaesbach G, Ogata T, Weksberg R, Algar E and Lapunzina P (2016) Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling. Eur J Hum Genet 24:784-793.

67 Fitzgerald HC, Salamonsen LA, Rombauts LJ, Vollenhoven BJ and Edgell TA (2016) The proliferative phase underpins endometrial development: Altered cytokine profiles in uterine lavage fluid of women with idiopathic infertility. Cytokine 88:12-19.

59 Eggers S, Sadedin S, van den Bergen JA, Robevska G, Ohnesorg T, Hewitt J, Lambeth L, Bouty A, Knarston IM, Tan TY, Cameron F, Werther G, Hutson J, O’Connell M, Grover SR, Heloury Y, Zacharin M, Bergman P, Kimber C, Brown J, Webb N, Hunter MF, Srinivasan S, Titmuss A, Verge CF, Mowat D, Smith G, Smith J, Ewans L, Shalhoub C, Crock P, Cowell C, Leong GM, Ono M, Lafferty AR, Huynh T, Visser U, Choong CS, McKenzie F, Pachter N, Thompson EM, Couper J, Baxendale A, Gecz J, Wheeler BJ, Jefferies C, MacKenzie K, Hofman P, Carter P, King RI, Krausz C, van Ravenswaaij-Arts CM, Looijenga L, Drop S, Riedl S, Cools M, Dawson A, Juniarto AZ, Khadilkar V, Khadilkar A, Bhatia V, Dung VC, Atta I, Raza J, Thi Diem Chi N, Hao TK, Harley V, Koopman P, Warne G, Faradz S, Oshlack A, Ayers KL and Sinclair AH (2016) Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol 17:243.

69 Fuller PJ and Young MJ (2016) Endocrine affairs of the heart. Endocrinology 157:2578-2582.

60 Ellery SJ, Dickinson H, McKenzie M and Walker DW (2016) Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy - Creatine prophylaxis and the need for multi-organ protection. Neurochem Int 95:15-23. 61

Ellery SJ, LaRosa DA, Kett MM, Della Gatta PA, Snow RJ, Walker DW and Dickinson H (2016) Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice. Amino Acids 48:1819-1830.

62 Ellery SJ, Walker DW and Dickinson H (2016) Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy. Amino Acids 48:1807-1817.

68 Forster SC, Browne HP, Kumar N, Hunt M, Denise H, Mitchell A, Finn RD and Lawley TD (2016) HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes. Nucleic Acids Res 44:604-609.

70 Funder JW (2016) Apparent mineralocorticoid excess. J Steroid Biochem Mol Biol 165:151-153. 71

Funder JW (2016) The promiscuous mineralocorticoid receptor. Hypertension 67:839-840.

Funder JW (2016) The potential of ACTH in the genesis of primary aldosteronism. Frontiers In Endocrinology 7:40.

73 Funder JW (2016) Primary aldosteronism as a public health issue. Lancet Diabetes Endocrinol 4:972-973. 74 Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M and Young WF, Jr. (2016) The management of primary aldosteronism: Case detection, diagnosis, and treatment: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 101:1889-1916. 75 Funder JW and Rossi GP (2016) Adrenal vein sampling versus CT scanning in primary aldosteronism. Lancet Diabetes Endocrinol 4:886. 76 Galiana-Simal A, Olivares-Alvaro E, KlettMingo M, Ruiz-Roso MB, Ballesteros S, de Las Heras N, Fuller PJ, Lahera V and Martin-Fernandez B (2016) Proanthocyanidins block aldosteronedependent up-regulation of cardiac gamma ENaC and Nedd4-2 inactivation via SGK1. J Nutr Biochem 37:13-19. 77

Galinsky R, Lear CA, Yamaguchi K, Wassink G, Westgate JA, Bennet L and Gunn AJ (2016) Cholinergic and betaadrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep. Am J Physiol Regul Integr Comp Physiol 311:949-956.

2016 ANNUAL REPORT / 59

78 Garama DJ, White CL, Balic JJ and Gough DJ (2016) Mitochondrial STAT3: Powering up a potent factor. Cytokine 87:20-25. 79 Gargett CE, Deane JA and Schwab KE (2016) Reply: An update on endometrial stem cells and progenitors by Deepa Bhartiya. Hum Reprod Update 22:530-531. 80 Gargett CE and Gurung S (2016) Endometrial mesenchymal stem/stromal cells, their fibroblast progeny in endometriosis, and more. Biol Reprod 94:129. 81

Gargett CE, Schwab KE and Deane JA (2016) Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update 22:137-163.

82 Godsell J, Rudloff I, Kandane-Rathnayake R, Hoi A, Nold MF, Morand EF and Harris J (2016) Clinical associations of IL-10 and IL37 in systemic lupus erythematosus. Sci Rep 6:34604.

94 Ham S, Harrison C, Southwick G and Temple-Smith P (2016) Selection of internal control genes for analysis of gene expression in normal and diseased human dermal fibroblasts using qualitative real time-PCR. Exp Dermatol 25:911-914. 95 Hanafi MY, Abdelkhalek TM, Saad MI, Saleh MM, Haiba MM and Kamel MA (2016) Diabetes-induced perturbations are subject to intergenerational transmission through maternal line. J Physiol Biochem 72:316-326. 96 Hanafi MY, Saad MI, Abdelkhalek TM, Saleh MM and Kamel MA (2016) In utero nutritional manipulation provokes dysregulated adipocytokines production in F1 offspring in rats. Scientifica (Cairo) 2016:3892890.

83 Gopagondanahalli KR, Li J, Fahey M, Hunt RW, Jenkin G, Miller SL and Malhotra A (2016) Preterm hypoxicâ&#x20AC;&#x201C;ischemic encephalopathy. Front Pediatr 4:114.

97 Hanafi MY, Saleh MM, Saad MI, Abdelkhalek TM and Kamel MA (2016) Transgenerational effects of obesity and malnourishment on diabetes risk in F2 generation. Mol Cell Biochem 412:269280.

84 Gratton AM, Ye L, Brownfoot FC, Hannan NJ, Whitehead C, Cannon P, Deo M, Fuller PJ, Tong S and Kaituâ&#x20AC;&#x2122;u-Lino T (2016) Steroid sulfatase is increased in the placentas and whole blood of women with early-onset preeclampsia. Placenta 48:72-79.

98 Harris K, Burley H, McLachlan R, Bowman M, Macaldowie A, Taylor K, Chapman M and Chambers GM (2016) Socioeconomic disparities in access to assisted reproductive technologies in Australia. Reprod Biomed Online 33:575-584.

85 Greenall SA, Adams TE and Johns TG (2016) Incomplete target neutralization by the anti-cancer antibody rilotumumab. MAbs 8:246-252. 86 Greenall SA and Johns TG (2016) EGFRvIII: the promiscuous mutation. Cell Death Discov 2:16049.

99 Hart RJ, Doherty DA, Keelan JA, McLachlan R, Skakkebaek NE, Norman RJ, Dickinson JE, Pennell CE, Newnham JP, Hickey M and Handelsman DJ (2016) Early life events predict adult testicular function; data derived from the Western Australian (Raine) birth cohort. J Clin Endocrinol Metab 101:3333-3344.

87 Greening DW, Nguyen HP, Elgass K, Simpson RJ and Salamonsen LA (2016) Human endometrial exosomes contain hormonespecific cargo modulating trophoblast adhesive capacity: Insights into endometrialembryo interactions. Biol Reprod 94:38.

100 Hartung JC, Wilitzki S, Thio-Lluch M, Te Pas AB, Schmalisch G and Roehr CC (2016) Reliability of single-use PEEPvalves attached to self-inflating bags during manual ventilation of neonates - an in vitro study. PLoS One 11:e0150224.

88 Greening DW, Nguyen HP, Evans J, Simpson RJ and Salamonsen LA (2016) Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy: The role of ovarian steroid and pregnancy hormones. J Proteomics 144:99-112.

101 Heng S, Stephens AN, Jobling TW and Nie G (2016) Measuring PC activity in endocervical swab may provide a simple and non-invasive method to detect endometrial cancer in post-menopausal women. Oncotarget 7:46573-46578.

89 Guan Y, Liang G, Hawken PA, Meachem SJ, Malecki IA, Ham S, Stewart T, Guan LL and Martin GB (2016) Nutrition affects Sertoli cell function but not Sertoli cell numbers in sexually mature male sheep. Reprod Fert Develop 28:1152-1163.

102 Heng S, Stephens AN, Jobling TW and Nie G (2016) Total PC activity is increased in uterine lavage of post-menopausal endometrial but not ovarian cancer patients. J Cancer 7:1812-1814.

90 Gunatillake T, Yong HE, Dunk CE, Keogh RJ, Borg AJ, Cartwright JE, Whitley GS and Murthi P (2016) Homeobox gene TGIF1 is increased in placental endothelial cells of human fetal growth restriction. Reproduction 152:457-465. 91

Gurzov EN, Stanley WJ, Pappas EG, Thomas HE and Gough DJ (2016) The JAK-STAT pathway in obesity and diabetes. FEBS J 283:3002-3015.

92 Gustin S, Stringer J, Hogg K, Sinclair A and Western P (2016) FGF9, activin and TGFbeta promote testicular characteristics in an XX gonad organ culture model. Reproduction 152:529-543. 93 Gustin SE, Hogg K, Stringer JM, Rastetter RH, Pelosi E, Miles DC, Sinclair AH, Wilhelm D and Western PS (2016) WNT/betacatenin and p27/FOXL2 differentially regulate supporting cell proliferation in the developing ovary. Dev Biol 412:250-260.

103 Heng S, Vollenhoven B, Rombauts LJ and Nie G (2016) A high-throughput assay for the detection of alpha-dystroglycan N-terminus in human uterine fluid to determine uterine receptivity. J Biomol Screen 21:408-413. 104 Hewitson TD, Boon WC, Simpson ER, Smith ER and Samuel CS (2016) Estrogens do not protect, but androgens exacerbate, collagen accumulation in the female mouse kidney after ureteric obstruction. Life Sci 158:130-136. 105 Hirst JJ, Cumberland AL, Shaw JC, Bennett GA, Kelleher MA, Walker DW and Palliser HK (2016) Loss of neurosteroid-mediated protection following stress during fetal life. J Steroid Biochem Mol Biol 160:181188. 106 Hobson S, Acharya R, Lim R, Chan ST, Mockler J and Wallace E (2016) Role of activin A in the pathogenesis

of endothelial cell dysfunction in preeclampsia. Pregnancy Hypertension 6:130-133. 107 Hooper SB, Binder-Heschl C, Polglase GR, Gill AW, Kluckow M, Wallace EM, Blank D and Te Pas AB (2016) The timing of umbilical cord clamping at birth: physiological considerations. Matern Health Neonatol Perinatol 2:4. 108 Hooper SB, Te Pas AB and Kitchen MJ (2016) Respiratory transition in the newborn: a three-phase process. Arch Dis Child Fetal Neonatal Ed 101:266-271. 109 Horne RS, Fyfe KL, Odoi A, Athukoralage A, Yiallourou SR and Wong FY (2016) Dummy/pacifier use in preterm infants increases blood pressure and improves heart rate control. Pediatr Res 79:325332. 110 Hutt K and Findlay J (2016) Egg supply and demand. Australasian Science Magazine 37:17-19. 111 Isbel L, Prokopuk L, Wu H, Daxinger L, Oey H, Spurling A, Lawther AJ, Hale MW and Whitelaw E (2016) Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse. Elife 5:e15082. 112 Jarde T, Kass L, Staples M, Lescesen H, Carne P, Oliva K, McMurrick P and Abud HE (2016) ERBB3 positively correlates with intestinal stem cell markers but marks a distinct non proliferative cell population in colorectal cancer. PLoS One 10:e0138336. 113 Jarde T, Lloyd-Lewis B, Thomas M, Kendrick H, Melchor L, Bougaret L, Watson PD, Ewan K, Smalley MJ and Dale TC (2016) Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nat Commun 7:13207. 114 Jenkins BJ (2016) Multifaceted role of IRAK-M in the promotion of colon carcinogenesis via barrier dysfunction and STAT3 oncoprotein stabilization in tumors. Cancer Cell 29:615-617. 115 Johnson J, Lee W, Frazier AE, Vaghjiani V, Laskowski A, Rodriguez AL, Cagnone G, McKenzie M, White SJ, Nisbet DR, Thorburn DR and St John J (2016) Deletion of the complex I subunit NDUFS4 adversely modulates cellular differentiation. Stem Cells Dev 25:239250. 116 Johnson KE, Makanji Y, Temple-Smith P, Kelly EK, Barton PA, Al-Musawi SL, Mueller TD, Walton KL and Harrison CA (2016) Biological activity and in vivo halflife of pro-activin A in male rats. Mol Cell Endocrinol 422:84-92. 117 Jones MW, Elgass KD, Junker MD, de Jonge MD and van Riessen GA (2016) Molar concentration from sequential 2-D waterwindow X-ray ptychography and X-ray fluorescence in hydrated cells. Sci Rep 6:24280. 118 Kang Y, Baker MJ, Liem M, Louber J, McKenzie M, Atukorala I, Ang CS, Keerthikumar S, Mathivanan S and Stojanovski D (2016) Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability. Elife 5:e17463.

60 / HUDSON INSTITUTE OF MEDICAL RESEARCH

119 Kerr LT, Donoghue JF, Wilding AL and Johns TG (2016) Axitinib has antiangiogenic and antitumorigenic activity in myxoid liposarcoma. Sarcoma 2016:3484673. 120 Klein B, Haggeney T, Fietz D, Indumathy S, Loveland KL, Hedger M, Kliesch S, Weidner W, Bergmann M and Schuppe HC (2016) Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia. Hum Reprod 31:2192-2202. 121 Klionsky D, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H and Liaskos M, et. al. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd Edition). Autophagy 12:1222. 122 Koay HF, Gherardin NA, Enders A, Loh L, Mackay LK, Almeida CF, Russ BE, Nold-Petry CA, Nold MF, Bedoui S, Chen Z, Corbett AJ, Eckle SB, Meehan B, dâ&#x20AC;&#x2122;Udekem Y, Konstantinov IE, Lappas M, Liu L, Goodnow CC, Fairlie DP, Rossjohn J, Chong MM, Kedzierska K, Berzins SP, Belz GT, McCluskey J, Uldrich AP, Godfrey DI and Pellicci DG (2016) A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nat Immunol 17:1300-1311. 123 Kockx M, Glaros E, Kan B, Ng TW, Berbee JF, Deswaerte V, Nawara D, Quinn C, Rye KA, Jessup W, Rensen PC, Meikle PJ and Kritharides L (2016) Low-density lipoprotein receptor-dependent and lowdensity lipoprotein receptor-independent mechanisms of cyclosporin A-induced dyslipidemia. Arterioscler Thromb Vasc Biol 36:1338-1349. 124 Konig K, Guy KJ, Nold-Petry CA, Barfield CP, Walsh G, Drew SM, Veldman A, Nold MF and Casalaz DM (2016) BNP, troponin I, and YKL-40 as screening markers in extremely preterm infants at risk for pulmonary hypertension associated with bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 311:1076-1081. 125 Krishnan SM, Dowling JK, Ling YH, Diep H, Chan CT, Ferens D, Kett MM, Pinar A, Samuel CS, Vinh A, Arumugam TV, Hewitson TD, Kemp-Harper BK, Robertson AA, Cooper MA, Latz E, Mansell A, Sobey CG and Drummond GR (2016) Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/ salt-induced hypertension in mice. Br J Pharmacol 173:752-765. 126 Kroese JK, van Vonderen JJ, Narayen IC, Walther FJ, Hooper S and Te Pas AB (2016) The perfusion index of healthy term infants during transition at birth. Eur J Pediatr 175:475-479. 127 Kumar A, Nestel D, Stoyles S, East C, Wallace EM and White C (2016) Simulation based training in a publicly funded home birth programme in Australia: A qualitative study. Women Birth 29:47-53. 128 Landersdorfer CB, Nguyen TH, Lieu LT, Nguyen G, Bischof RJ, Meeusen EN, Li J, Nation RL and McIntosh MP (2016) Substantial targeting advantage achieved by pulmonary administration of colistin methanesulfonate: Insights from a large animal model. Antimicrob Agents Chemother 61:e01934-16. 129 Lang JA, Pearson JT, Binder-Heschl C, Wallace MJ, Siew ML, Kitchen MJ, Te Pas

AB, Fouras A, Lewis RA, Polglase GR, Shirai M and Hooper SB (2016) Increase in pulmonary blood flow at birth; role of oxygen and lung aeration. J Physiol 594:1389-1398. 130 LaRosa DA, Ellery SJ, Parkington HC, Snow RJ, Walker DW and Dickinson H (2016) Maternal creatine supplementation during pregnancy prevents long-term changes in diaphragm muscle structure and function after birth asphyxia. PLoS One 11:e0149840. 131 LaRosa DA, Ellery SJ, Snow RJ, Walker DW and Dickinson H (2016) Maternal creatine supplementation during pregnancy prevents acute and long-term deficits in skeletal muscle after birth asphyxia: a study of structure and function of hind limb muscle in the spiny mouse. Pediatr Res 80:852-860. 132 Lee PH, Bird N, MacKenzie-Kludas C, Mansell A, Kedzierska K, Brown L and McAuley J (2016) Induction of memory cytotoxic T cells to influenza A virus and subsequent viral clearance is not modulated by PB1-F2-dependent inflammasome activation. Immunol Cell Biol 94:439-446. 133 Lee W, Cain J, Cuddihy A, Johnson J, Dickinson A, Yeung KY, Kumar B, Johns T, Watkins DN, Spencer A and St .John JC (2016) Mitochondrial DNA plasticity is an essential inducer of tumorigenesis. Cell Death Discov 2:16016. 134 Lee WT and St John JC (2016) Mitochondrial DNA as an initiator of tumorigenesis. Cell Death Dis 7:e2171. 135 Leung DT, Fuller PJ and Chu S (2016) Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors. Int J Biochem Cell Biol 72:51-54. 136 Li J, Funato M, Tamai H, Wada H, Nishihara M, Morita T, Miller SL and Egashira K (2016) Impact of intra- and extrauterine growth on bone mineral density and content in the neonatal period of verylow-birth-weight infants. Early Hum Dev 92:1-6. 137 Li J, Yawno T, Sutherland A, Loose J, Nitsos I, Bischof R, Castillo-Melendez M, McDonald CA, Wong FY, Jenkin G and Miller SL (2016) Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells. Exp Neurol 283:179-187. 138 Li Y, Basavappa M, Lu J, Dong S, Cronkite DA, Prior JT, Reinecker HC, Hertzog P, Han Y, Li WX, Cheloufi S, Karginov FV, Ding SW and Jeffrey KL (2016) Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells. Nat Microbiol 2:16250. 139 Liew SH, Vaithiyanathan K and Hutt KJ (2016) Taking control of the female fertile lifespan: A key role for Bcl-2 family proteins. Reprod Fertil Dev 28:864-871. 140 Lim SC, Hroudova J, Van Bergen NJ, Lopez Sanchez MI, Trounce IA and McKenzie M (2016) Loss of mitochondrial DNAencoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly. FASEB J 30:22362248. 141 Liu JP (2016) Novel strategies for molecular targeting to cancer. Clin Exp Pharmacol Physiol 43:287-289.

142 Lo CY, Chen S, Creed SJ, Kang M, Zhao N, Tang BZ and Elgass KD (2016) Novel super-resolution capable mitochondrial probe, MitoRed AIE, enables assessment of real-time molecular mitochondrial dynamics. Sci Rep 6:30855. 143 Low M, Infantino S, Grigoriadis G and Tarlinton D (2016) Targeting plasma cells: Are we any closer to a panacea for diseases of antibody-secreting cells? Immunol Rev 270:78-94. 144 Low MS, Vilcassim S, Fedele P and Grigoriadis G (2016) Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction. Intern Med J 46:497-499. 145 Low MS, Vilcassim S, Fedele P and Grigoriadis G (2016) Acute monocytic leukemia masked by hemolytic anemia and sclerotic lesions. Ann Hematol 95:2081-2082. 146 Ludbrook L, Alankarage D, BagheriFam S and Harley V (2016) Dataset of differentially expressed genes from SOX9 over-expressing NT2/D1 cells. Data Brief 9:194-198. 147 Maeda Y, Echizen K, Oshima H, Yu L, Sakulsak N, Hirose O, Yamada Y, Taniguchi T, Jenkins BJ, Saya H and Oshima M (2016) Myeloid differentiation factor 88 signaling in one marrow-derived cells promotes gastric tumorigenesis by generation of inflammatory microenvironment. Cancer Prev Res (Phila) 9:253-263. 148 Maifiah M, Cheah S-E, Johnson M, Han M, Boyce JD, Thamlikitful V, Forrest A, Hertzog P, Purcell AW, Song J, Velkov T, Creek D and Li J (2016) Global metabolic analyses identify key differences in metabolite levels between polymyxinsusceptible and polymyxin-resistant Acinetobacter baumanni. Sci Rep 6:22287. 149 Malaver-Ortega LF, Sumer H, Jain K and Verma PJ (2016) Bone morphogenetic protein 4 and retinoic acid trigger bovine VASA homolog expression in differentiating bovine induced pluripotent stem cells. Mol Reprod Dev 83:149-161. 150 Malhotra A, Fahey M, Miller SL, Jenkin G, Singh JV, Patil P, Kumar V and Wallace EM (2016) Developing a culturally sensitive training program for recognition of hypoxic ischemic encephalopathy in rural India. Int J Pediatr Res 2:024. 151 Martin OA, Yin X, Forrester HB, Sprung CN and Martin RF (2016) Potential strategies to ameliorate risk of radiotherapy-induced second malignant neoplasms. Semin Cancer Biol 37-38:65-76. 152 McCabe MJ, Foo CF, Dinger ME, Smooker PM and Stanton PG (2016) Claudin-11 and occludin are major contributors to Sertoli cell tight junction function. Asian J Androl 18:620-626. 153 McCabe MJ, Tarulli GA, Laven-Law G, Matthiesson KL, Meachem SJ, McLachlan RI, Dinger ME and Stanton PG (2016) Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction. Hum Reprod 31 875-886. 154 McKenzie M and Duchen MR (2016) Impaired cellular bioenergetics causes mitochondrial calcium handling defects

2016 ANNUAL REPORT / 61

in MT-ND5 mutant cybrids. PLoS One 11:e0154371. 155 McNamara KM, Oguro S, Omata F, Kikuchi K, Guestini F, Suzuki K, Yang Y, Abe E, Hirakawa H, Brown KA, Takanori I, Ohuchi N and Sasano H (2016) The presence and impact of estrogen metabolism on the biology of triple-negative breast cancer. Breast Cancer Res Treat 161:213-227. 156 Menheniott TR, Oâ&#x20AC;&#x2122;Connor L, Chionh YT, Dabritz J, Scurr M, Rollo BN, Ng GZ, Jacobs S, Catubig A, Kurklu B, Mercer S, Minamoto T, Ong DE, Ferrero RL, Fox JG, Wang TC, Sutton P, Judd LM and Giraud AS (2016) Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression. J Clin Invest 126:13831400. 157 Menkhorst E, Winship A, Van Sinderen M and Dimitriadis E (2016) Human extravillous trophoblast invasion: intrinsic and extrinsic regulation. Reprod Fertil Dev 28:406-415. 158 Michel V, Duan Y, Stoschek E, Bhushan S, Middendorff R, Young JM, Loveland KA, Kretser DM, Hedger MP and Meinhardt A (2016) Uropathogenic Escherichia coli cause fibrotic remodelling of the epididymis. J Pathol 240:15-24. 159 Milat F and Ebeling PR (2016) Osteoporosis treatment: a missed opportunity. Med J Aust 205:185-190. 160 Miller SL, Huppi PS and Mallard C (2016) The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome. J Physiol 594:807-823. 161 Monhasery N, Moll J, Cuman C, Franke M, Lamertz L, Nitz R, Gorg B, Haussinger D, Lokau J, Floss DM, Piekorz R, Dimitriadis E, Garbers C and Scheller J (2016) Transcytosis of IL-11 and apical redirection of gp130 is mediated by IL-11alpha receptor. Cell Rep 16:1067-1081. 162 Mulatero P, Monticone S, Burrello J, Veglio F, Williams TA and Funder J (2016) Guidelines for primary aldosteronism: uptake by primary care physicians in Europe. J Hypertens 34:2253-2257. 163 Murthi P, Yong HE, Ngyuen TP, Ellery S, Singh H, Rahman R, Dickinson H, Walker DW, Davies-Tuck M, Wallace EM and Ebeling PR (2016) Role of the placental vitamin D receptor in modulating feto-placental growth in fetal growth restriction and preeclampsia-affected pregnancies. Front Physiol 7:43. 164 Muscat A, Popovski D, Jayasekara WS, Rossello FJ, Ferguson MJ, Marini KM, Alamgeer M, Algar E, Downie PA, Watkins N, Cain JE and Ashley DM (2016) Low-dose histone deacetylase inhibitor treatment leads to tumour growth arrest and multi-lineage differentiation of malignant rhabdoid tumours. Clin Cancer Res 22:3560-3570. 165 Nagase M, Kurihara H, Aiba A, Young MJ and Sakai T (2016) Deletion of Rac1GTPase in the myeloid lineage protects against inflammation-mediated kidney injury in mice. PLoS One 11:e0150886. 166 Naidu MA, Muljadi R, Davies-Tuck ML, Wallace EM and Giles ML (2016) The optimal gestation for pertussis

vaccination during pregnancy - A prospective cohort study. Am J Obstet Gynecol 215:237. e1-6. 167 Nefzger CM, Jarde T, Rossello FJ, Horvay K, Knaupp AS, Powell DR, Chen J, Abud HE and Polo JM (2016) A versatile strategy for isolating a highly enriched population of intestinal stem cells. Stem Cell Rep 6:321-329. 168 Nguyen HP, Simpson RJ, Salamonsen LA and Greening DW (2016) Extracellular vesicles in the intrauterine environment: Challenges and potential functions. Biol Reprod 95:109. 169 Nixon GM, Biggs SN, Jitpiriyaroj S and Horne RS (2016) The relationship between sleep-disordered breathing severity and daytime adaptive functioning in children with Down syndrome. CNS Neurosci Ther 22:936-937. 170 Nixon GM, Davey MJ, Weichard AJ and Horne RS (2016) Oximetry for suspected obstructive sleep apnea - Does removal of awake data affect the result? Pediatr Pulmonol 51:1409-1413. 171 Nixon GM and Hamilton GS (2016) Does anyone in your family have obstructive sleep apnea? J Clin Sleep Med 12:941-942. 172 Novak I, Walker K, Hunt RW, Wallace EM, Fahey M and Badawi N (2016) Concise Review: Stem cell interventions for people with cerebral palsy: Systematic review with meta-analysis. Stem Cells Transl Med 5:1014-1025. 173 Novakovic B, Napier CE, Vryer R, Dimitriadis E, Manuelpillai U, Sharkey A, Craig JM, Reddel RR and Saffery R (2016) DNA methylation mediated up-regulation of TERRA non-coding RNA is coincident with elongated telomeres in the human placenta. Mol Hum Reprod 22:791-799. 174 Nsiah-Sefaa A and McKenzie M (2016) Combined defects in oxidative phosphorylation and fatty acid betaoxidation in mitochondrial disease. Biosci Rep 36:e00313. 175 Oehme D, Ghosh P, Goldschlager T, Itescu S, Shimon S, Wu J, McDonald C, Troupis JM, Rosenfeld JV and Jenkin G (2016) Reconstitution of degenerated ovine lumbar discs by STRO-3-positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate. J Neurosurg Spine 24:715-726. 176 Ong T, Sobotka KS, Siew ML, Crossley KJ, van Vonderen JJ, Polglase GR and Hooper SB (2016) The cardiovascular response to birth asphyxia is altered by the surrounding environment. Arch Dis Child Fetal Neonatal Ed 101:540-545. 177 Panagodage S, Juen Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP and Murthi P (2016) Low-dose acetylsalicylic acid treatment modulates the production of cytokines and improves trophoblast function in an in vitro model of early-onset preeclampsia. Am J Pathol 186:3217-3224. 178 Parker BS, Rautela J and Hertzog P (2016) Anti-tumour actions of type I inteferons: implications for cancer therapy. Nat Rev Cancer 16:131-144. 179 Parkinson LA, Gargett CE, Young N, Rosamilia A, Vashi AV, Werkmeister JA,

Papageorgiou AW and Arkwright JW (2016) Real-time measurement of the vaginal pressure profile using an opticalfiber-based instrumented speculum. J Biomed Opt 21:127008. 180 Pathirana R and Kaparakis-Liaskos M (2016) Bacterial membrane vesicles: biogenesis, immune regulation and pathogenesis. Cell Microbiol 18:15181524. 181 Pease AS, Fleming PJ, Hauck FR, Moon RY, Horne RS, Lâ&#x20AC;&#x2122;Hoir MP, Ponsonby AL and Blair PS (2016) Swaddling and the risk of sudden infant death syndrom: A metaanalysis. Pediatrics 137:e20153275. 182 Pepin G, Ferrand J, Honing K, Jayasekara WS, Cain JE, Behlke MA, Gough DJ, Williams BRG, Hornung V and Gantier MP (2016) Cre-dependent DNA recombination activates a STING-dependent innate immune response. Nucleic Acids Res 44:5356-5364. 183 Pepin G and Gantier MP (2016) MicroRNA decay: Refining microRNA regulatory activity. MicroRNA 5:167-174. 184 Polglase GR, Allison BJ, Coia E, Li A, G J, Malhotra A, Sehgal A, Kluckow M, Gill AW, Hooper SB and Miller SL (2016) Altered cardiovascular function at birth in growth restricted preterm lambs. Pediatr Res 80:538-546. 185 Polglase GR, Ong T and Hillman NH (2016) Cardiovascular alterations and multiorgan dysfunction after birth asphyxia. Clin Perinatol 43:469-483. 186 Prescott SL, Allen K, Armstrong K, Collins C, Dickinson H, Gardiner K, Jacka F, Jasoni C, Moore T, Moritz KM, Muhlhausler B, Siero W, Sim K, Nanan R, Saffery R, Singh G, Vickers MH and Craig JM (2016) The establishment of DOHaD working groups in Australia and New Zealand. J Dev Orig Health Dis 7:433-439. 187 Puttemans P, Benagiano G, Gargett C, Romero R, Guo SW and Brosens I (2016) Neonatal uterine bleeding as a biomarker for reproductive disorders during adolescence: a worldwide call for systematic registration by nurse midwife. J Matern Fetal Neonatal Med 18:1-3. 188 Qadi AA, Taberlay PC, Phillips JL, Young A, West AC, Brettingham-Moore KH, Dickinson JL and Holloway AF (2016) The leukemia inhibitory factor receptor gene is a direct target of RUNX1. J Cell Biochem 117:49-28. 189 Quinn JA, Munoz FM, Gonik B, Frau L, Cutland C, Mallett-Moore T, Kissou A, Wittke F, Das M, Nunes T, Pye S, Watson W, Ramos AA, Cordero JF, Huang WT, Kocchar S, Buttery J and Brighton Collaboration Preterm Birth Working Group (2016) Preterm birth: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine 34:6047-6056. 190 Quinn TA, Ratnayake U, Dickinson H, Castillo-Melendez M and Walker DW (2016) Ontogenetic change in the regional distribution of dehydroepiandrosteronesynthesizing enzyme and the glucocorticoid receptor in the brain of the spiny mouse (Acomys cahirinus). Dev Neurosci 38 54-73.

62 / HUDSON INSTITUTE OF MEDICAL RESEARCH

191 Quinn TA, Ratnayake U, Dickinson H, Castillo-Melendez M and Walker DW (2016) The feto-placental unit, and potential roles of dehydroepiandrosterone (DHEA) in prenatal and postnatal brain development: A re-examination using the spiny mouse. J Steroid Biochem Mol Biol 160:204-213. 192 Rahman R, Murthi P, Singh H, Gurusinghe S, Mockler JC, Lim R and Wallace EM (2016) The effects of hydroxychloroquine on endothelial dysfunction. Pregnancy Hypertens 6:259-262. 193 Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen MC, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DP, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Nageswara Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognar L, Klekner A, Hortobagyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tunon T, Schuller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher PG, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW and Taylor MD (2016) Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis. J Clin Oncol 34:2468-2477. 194 Robertson DM, Gilchrist RB, Ledger WL and Baerwald A (2016) Random start or emergency IVF/in vitro maturation: a new rapid approach to fertility preservation. Womens Health (Lond Engl) 12:339-349. 195 Robertson DM, Lee CH and Baerwald A (2016) Interrelationships among reproductive hormones and antral follicle count in human menstrual cycles. Endocr Connect 5:98-107. 196 Rogers P, Adamson GD, Al-Jefout M, Becker CM, Dâ&#x20AC;&#x2122;Hooghe T, Dunselman GA, Fazleabas A, Giudice LC, Horne AW, Hull ML, Hummelshoj L, Missmer SA, Montgomery GW, Stratton P, Taylor RN, Rombauts L, Saunders PT, Vincent K, Zondervan KT and WES/WERF Consortium for Research Priorities in Endometriosis (2016) Research priorities for endometriosis: recommendations from a global consortium of investigators in endometriosis. Reprod Sci 24:202-226. 197 Royce SG, Nold MF, Bui C, Donovan C, Lam M, Lamanna E, Rudloff I, Bourke JE and Nold-Petry CA (2016) Airway remodeling and hyperreactivity in a model of bronchopulmonary dysplasia and their modulation by IL-1Ra. Am J Respir Cell Mol Biol 55:858-868.

198 Royce SG, Tominaga AM, Shen M, Patel KP, Huuskes BM, Lim R, Ricardo SD and Samuel CS (2016) Serelaxin improves the therapeutic efficacy of RXFP1expressing human amnion epithelial cells in experimental allergic airways disease. Clin Sci (Lond) 130:2151-2165.

209 Shen JZ, Morgan J, Tesch GH, Rickard AJ, Chrissobolis S, Drummond GR, Fuller PJ and Young MJ (2016) Cardiac tissue injury and remodeling is dependent upon MR regulation of activation pathways in cardiac tissue macrophages. Endocrinology 157:3213-3223.

199 Ruwanpura SM, McLeod L, Dousha LF, Seow HJ, Alhayyani S, Tate MD, Deswaerte V, Brooks GD, Bozinovski S, MacDonald M, Garbers C, King PT, Bardin PG, Vlahos R, Rose-John S, Anderson GP and Jenkins BJ (2016) Therapeutic targeting of the IL-6 trans-signalling/mTORC1 axis in pulmonary emphysema. Am J Respir Crit Care Med 194:1494-1505.

210 Sigston EA, Longano A, Strzelecki AT and Williams BR (2016) Surgical margins in head and neck squamous cell carcinoma: Effect of heat artifact on immunohistochemistry as a future tool for assessment. Head Neck 38:1401-1406.

200 Saad MI, Abdelkhalek TM, Haiba MM, Saleh MM, Hanafi MY, Tawfik SH and Kamel MA (2016) Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring. J Endocrinol Invest 39:643-655. 201 Saad MI, Abdelkhalek TM, Saleh MM, Haiba MM, Tawfik SH and Kamel MA (2016) Maternal diabetes impairs oxidative and inflammatory response in murine placenta. Springerplus 5:532. 202 Salamonsen LA, Evans J, Nguyen HP and Edgell TA (2016) The microenvironment of human implantation: determinant of reproductive success. Am J Reprod Immunol 75:218-225.

211 Sinha D, Chong L, George J, Schluter H, Monchgesang S, Mills S, Li J, Parish C, Bowtell D, Kaur P and Australian Ovarian Cancer Study Group (2016) Pericytes promote malignant ovarian cancer progression in mice and predict poor prognosis in serous ovarian cancer patients. Clin Cancer Res 22:1813-1824. 212 Skalamera D, Dahmer-Heath M, Stevenson AJ, Pinto C, Shah ET, Daignault SM, Said NA, Davis M, Haass NK, Williams ED, Hollier BG, Thompson EW, Gabrielli B and Gonda TJ (2016) Genome-wide gain-offunction screen for genes that induce epithelial-to-mesenchymal transition in breast cancer. Oncotarget 7:6100061020.

203 Samardzija C, Luwor RB, Quinn MA, Kannourakis G, Findlay JK and Ahmed N (2016) Coalition of Oct4A and beta1 integrins in facilitating metastasis in ovarian cancer. BMC Cancer 16:432.

213 Sobotka KS, Hooper SB, Crossley KJ, Ong T, Schmolzer GM, Barton SK, McDougall AR, Miller SL, Tolcos M, Klingenberg C and Polglase GR (2016) Single sustained inflation followed by ventilation leads to rapid cardiorespiratory recovery but causes cerebral vascular leakage in asphyxiated near-term lambs. PLoS One 11:e0146574.

204 Sands SA, Edwards BA, Kee K, StuartAndrews C, Skuza EM, Roebuck T, Turton A, Hamilton GS, Naughton MT and Berger PJ (2016) Control theory prediction of resolved Cheyne-Stokes respiration in heart failure. Eur Respir J 48:1351-1359.

214 Sooraj D, Xu D, Cain JE, Gold DP and Williams BRG (2016) Activating transcription factor 3 expression as a marker of response to the histone deacetylase inhibitor pracinostat. Mol Cancer Ther 15:1726-1739.

205 Schagdarsurengin U, Western P, Steger K and Meinhardt A (2016) Developmental origins of male subfertility: role of infection, inflammation, and environmental factors. Semin Immunopathol 38:765-781.

215 St John JC (2016) Mitochondrial DNA copy number and replication in reprogramming and differentiation. Semin Cell Dev Biol 52:93-101.

206 Sebina I, James KR, Soon MS, Fogg LG, Best SE, Labastida Rivera F, Montes de Oca M, Amante FH, Thomas BS, Beattie L, Souza-Fonseca-Guimaraes F, Smyth MJ, Hertzog PJ, Hill GR, Hutloff A, Engwerda CR and Haque A (2016) IFNAR1-signalling obstructs ICOS-mediated humoral immunity during non-lethal blood-stage Plasmodium infection. PLoS Pathog 12:e1005999. 207 Sergent F, Hoffmann P, Brouillet S, Garnier V, Salomon A, Murthi P, Benharouga M, Feige JJ and Alfaidy N (2016) Sustained endocrine gland-derived vascular endothelial growth factor levels beyond the first trimester of pregnancy display phenotypic and functional changes associated with the pathogenesis of pregnancy-induced hypertension. Hypertension 68:148-156. 208 Shapouri F, Saeidi S, de Longh R, Casagranda F, Western P, McLaughlin E, Sutherland J, Hime G and Familari M (2016) Tob1 is expressed in the developing and adult gonads and is localised to P-body marker, Dcp2. Cell Tissue Res 364:443-451.

216 St John JC, Tsai TS and Cagnone GL (2016) Mitochondrial DNA supplementation as an enhancer of female reproductive capacity. Curr Opin Obstet Gynecol 28:211-216. 217 Stanton PG (2016) Regulation of the blood-testis barrier. Semin Cell Dev Biol 59:166-173. 218 Stanton PG, Foo CF, Rainczuk A, Stephens AN, Condina M, Oâ&#x20AC;&#x2122;Donnell L, Weidner W, Ishikawa T, Cruickshanks L, Smith LB and McLachlan RI (2016) Mapping the testicular interstitial fluid proteome from normal rats. Proteomics 16:2391-2402. 219 Subbaramaiah K, Brown KA, Zahid H, Balmus G, Weiss RS, Herbert BS and Dannenberg AJ (2016) Hsp90 and PKM2 drive the expression of aromatase in Li-Fraumeni Syndrome breast adipose stromal cells. J Biol Chem 291:1601116023. 220 Sun X and St John JC (2016) The role of the mtDNA set point in differentiation, development and tumorigenesis. Biochem J 473:2955-2971. 221 Tamanyan K, Walter LM, Davey MJ, Nixon GM, Horne RS and Biggs SN (2016) Risk

2016 ANNUAL REPORT / 63

factors for obstructive sleep apnoea in Australian children. J Paediatr Child Health 52:512-517. 222 Tate MD, Ong JD, Dowling JK, McAuley JL, Robertson AB, Latz E, Drummond GR, Cooper MA, Hertzog PJ and Mansell A (2016) Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Sci Rep 6:27912. 223 Te Pas AB, Kitchen MJ, Lee K, Wallace MJ, Fouras A, Lewis RA, Yagi N, Uesugi K and Hooper SB (2016) Optimizing lung aeration at birth using a sustained inflation and positive pressure ventilation in preterm rabbits. Pediatr Res 80:85-91. 224 Te Pas AB, Sobotka K and Hooper SB (2016) Novel approaches to neonatal resuscitation and the impact on birth asphyxia. Clin Perinatol 43:455-467. 225 Thomas BJ, Kan OK, Loveland K, Elias JA and Bardin PG (2016) In the shadow of fibrosis: Innate immune suppression mediated by transforming growth factor beta. Am J Respir Cell Mol Biol 55:759766. 226 Tiwari A, Tursky ML, Nekkanti LP, Jenkin G, Kirkland MA and Pande G (2016) Expansion of human hematopoietic stem/ progenitor cells on decellularized matrix scaffolds. Curr Protoc Stem Cell Biol 36:1C.15.1-1C.15.16. 227 Tiwari A, Wong CS, Nekkanti LP, Deane JA, McDonald C, Jenkin G and Kirkland MA (2016) Impact of oxygen levels on human hematopoietic stem and progenitor cell expansion. Stem Cells Dev 25:1604-1613. 228 Toon E, Davey MJ, Hollis SL, Nixon GM, Horne RS and Biggs SN (2016) Comparison of commercial wrist-based and smartphone accelerometers, actigraphy, and PSG in a clinical cohort of children and adolescents. J Clin Sleep Med 12:343-350. 229 Trinh A, Chan I, Alexiadis MP, Pell M, Kumar B and Fuller P (2016) Adrenal Cushing’s Syndrome in pregnancy: clinical and molecular characterisation of a case. Obstetric Medicine 9:43-45. 230 Trinh A, Wong P, Ebeling PR, Fuller PJ and Milat F (2016) Severe acute phase response after intravenous zoledronic acid in adult patients with cerebral palsy. Intern Med J 46:506-507. 231 Trinh A, Wong P, Fahey MC, Brown J, Churchyard A, Strauss BJ, Ebeling PR, Fuller PJ and Milat F (2016) Musculoskeletal and endocrine health in adults with cerebral palsy: new opportunities for intervention. J Clin Endocrinol Metab 101:1190-1197. 232 Trounson A and DeWitt ND (2016) Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol 17:194-200. 233 Tsai T and St John JC (2016) The role of mitochondrial DNA copy number, variants, and haplotypes in farm animal developmental outcome. Domest Anim Endocrinol 56:133-146. 234 Tsai TS, Rajasekar S and St John JC (2016) The relationship between mitochondrial DNA haplotype and the reproductive capacity of domestic pigs (Sus scrofa domesticus). BMC Genet 17:67.

235 Ullah MO, Sweet MJ, Mansell A, Kellie S and Kobe B (2016) TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target. J Leukoc Biol 100:2745. 236 Ulrich D, Edwards SL, Alexander DL, Rosamilia A, Werkmeister JA, Gargett CE and Letouzey V (2016) Changes in pelvic organ prolapse mesh mechanical properties following implantation in rats. Am J Obstet Gynecol 214:260 e1-8. 237 Vaithiyanathan K, Liew SH, Zerafa N, Gamage T, Cook M, O’Reilly LA, Bouillet P, Scott CL, Strasser A, Findlay JK and Hutt KJ (2016) BCL2-modifying factor promotes germ cell loss during murine oogenesis. Reproduction 151:553-562. 238 van Vonderen JJ, van Zanten HA, Schilleman K, Hooper SB, Kitchen MJ, Witlox RS and Te Pas AB (2016) Cardiorespiratory monitoring during neonatal resuscitation for direct feedback and audit. Front Pediatr 4:38. 239 Van Voorhis WC, Adams JH, Adelfio R, Ahyong V, Akabas MH, Alano P, Alday A, Aleman Resto Y, Alsibaee A, Alzualde A, Andrews KT, Avery SV, Avery VM, Ayong L, Baker M, Baker S, Ben Mamoun C, Bhatia S, Bickle Q, Bounaadja L, Bowling T, Bosch J, Boucher LE, Boyom FF, Brea J, Brennan M, Burton A, Caffrey CR, Camarda G, Carrasquilla M, Carter D, Belen Cassera M, Chih-Chien Cheng K, Chindaudomsate W, Chubb A, Colon BL, Colon-Lopez DD, Corbett Y, Crowther GJ, Cowan N, D’Alessandro S, Le Dang N, Delves M, DeRisi JL, Du AY, Duffy S, Abd El-Salam El-Sayed S, Ferdig MT, Fernandez Robledo JA, Fidock DA, Florent I, Fokou PV, Galstian A, Gamo FJ, Gokool S, Gold B, Golub T, Goldgof GM, Guha R, Guiguemde WA, Gural N, Guy RK, Hansen MA, Hanson KK, Hemphill A, Hooft van Huijsduijnen R, Horii T, Horrocks P, Hughes TB, Huston C, Igarashi I, Ingram-Sieber K, Itoe MA, Jadhav A, Naranuntarat Jensen A, Jensen LT, Jiang RH, Kaiser A, Keiser J, Ketas T, Kicka S, Kim S, Kirk K, Kumar VP, Kyle DE, Lafuente MJ, Landfear S, Lee N, Lee S, Lehane AM, Li F, Little D, Liu L, Llinas M, Loza MI, Lubar A, Lucantoni L, Lucet I, Maes L, Mancama D, Mansour NR, March S, McGowan S, Medina Vera I, Meister S, Mercer L, Mestres J, Mfopa AN, Misra RN, Moon S, Moore JP, Morais Rodrigues da Costa F, Muller J, Muriana A, Nakazawa Hewitt S, Nare B, Nathan C, Narraidoo N, Nawaratna S, Ojo KK, Ortiz D, Panic G, Papadatos G, Parapini S, Patra K, Pham N, Prats S, Plouffe DM, Poulsen SA, Pradhan A, Quevedo C, Quinn RJ, Rice CA, Abdo Rizk M, Ruecker A, St Onge R, Salgado Ferreira R, Samra J, Robinett NG, Schlecht U, Schmitt M, Silva Villela F, Silvestrini F, Sinden R, Smith DA, Soldati T, Spitzmuller A, Stamm SM, Sullivan DJ, Sullivan W, Suresh S, Suzuki BM, Suzuki Y, Swamidass SJ, Taramelli D, Tchokouaha LR, Theron A, Thomas D, Tonissen KF, Townson S, Tripathi AK, Trofimov V, Udenze KO, Ullah I, Vallieres C, Vigil E, Vinetz JM, Voong Vinh P, Vu H, Watanabe NA, Weatherby K, White PM, Wilks AF, Winzeler EA, Wojcik E, Wree M, Wu W, Yokoyama N, Zollo PH, Abla N, Blasco B, Burrows J, Laleu B, Leroy D, Spangenberg T, Wells T and Willis PA (2016) Open source drug discovery with the Malaria Box compound collection for neglected diseases and beyond. PLoS Pathog 12:e1005763.

240 Vento G, Pastorino R, Boni L, Cota F, Carnielli V, Cools F, Dani C, Mosca F, Pillow J, Polglase G, Tagliabue P, van Kaam AH, Ventura ML, Tana M, Tirone C, Aurilia C, Lio A, Ricci C, Gambacorta A, Consigli C, D’Onofrio D, Gizzi C, Massenzi L, Cardilli V, Casati A, Bottino R, Pontiggia F, Ciarmoli E, Martinelli S, Ilardi L, Colnaghi M, Matassa PG, Vendettuoli V, Villani P, Fusco F, Gazzolo D, Ricotti A, Ferrero F, Stasi I, Magaldi R, Maffei G, Presta G, Perniola R, Messina F, Montesano G, Poggi C, Giordano L, Roma E, Grassia C, Ausanio G, Sandri F, Mescoli G, Giura F, Garani G, Solinas A, Lucente M, Nigro G, Del Vecchio A, Petrillo F, Orfeo L, Grappone L, Quartulli L, Scorrano A, Messner H, Staffler A, Gargano G, Balestri E, Nobile S, Cacace C, Meli V, Dallaglio S, Pasqua B, Mattia L, Gitto E, Vitaliti M, Re MP, Vedovato S, Grison A, Berardi A, Torcetta F, Guidotti I, di Fabio S, Maranella E, Mondello I, Visentin S and Tormena F (2016) Efficacy of a new technique - INtubate-RECruitSURfactant-Extubate - “IN-REC-SUR-E” - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial. Trials 17:414. 241 Verbeek C, van Zanten HA, van Vonderen JJ, Kitchen MJ, Hooper SB and Te Pas AB (2016) Accuracy of currently available neonatal respiratory function monitors for neonatal resuscitation. Eur J Pediatr 175:1065-1070. 242 Verbeek L, Zhao DP, Te Pas AB, Middeldorp JM, Hooper SB, Oepkes D and Lopriore E (2016) Hemoglobin differences in uncomplicated monochorionic twins in relation to birth order and mode of delivery. Twin Res Hum Genet 19:241-245. 243 Visvanathan K, Lang T, Ryan K, Wilson R, Skinner NA, Thompson AJ, Ahn SH, Weilert F, Abbott W, Gane E, Colledge D, Li K, Locarnini S, Mansell A and Revill PA (2016) Toll-IL1 receptor-mediated innate immune responses vary across HBV genotype and predict treatment response to pegylated-IFN in HBeAg-positive CHB patients. J Viral Hepat 23:170-179. 244 Walker EC, Johnson RW, Hu Y, Brennan HJ, Poulton IJ, Zhang JG, Jenkins BJ, Smyth GK, Nicola NA and Sims NA (2016) Murine oncostatin M acts via leukemia inhibitory factor receptor to phosphorylate STAT3 but not STAT1, an effect that protects bone mass. J Biol Chem 291:21703-21716. 245 Walter LM, Biggs SN, Cikor N, Rowe K, Davey MJ, Horne RS and Nixon GM (2016) The efficacy of the OSA-18 as a waiting list triage tool for OSA in children. Sleep Breath 20:837-844. 246 Walter LM, Biggs SN, Nisbet LC, Weichard AJ, Hollis SL, Davey MJ, Anderson V, Nixon GM and Horne RS (2016) Improved long-term autonomic function following resolution of sleep-disordered breathing in preschool-aged children. Sleep Breath 20:309-319. 247 Walton KL, Kelly EK, Johnson KE, Robertson DM, Stanton PG and Harrison CA (2016) A novel, more efficient, approach to generate bioactive inhibins. Endocrinology 157:2799-2809. 248 Wang T, Shigdar S, Shamaileh HA, Gantier MP, Yin W, Xiang D, Wang L, Zhou SF, Hou Y, Wang P, Zhang W, Pu C and Duan W (2016) Challenges and opportunities for siRNA-based cancer treatment. Cancer Lett 387:77-83.

64 / HUDSON INSTITUTE OF MEDICAL RESEARCH

249 Wang Y, Bilandzic M, Ooi GT, Findlay JK and Stenvers KL (2016) Endogenous inhibins regulate steroidogenesis in mouse TM3 Leydig cells by altering SMAD2 signalling. Mol Cell Endocrinol 436:68-77. 250 Wang Y and Nie G (2016) High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells. Placenta 47:46-55. 251 Weichard AJ, Walter LM, Hollis SL, Nixon GM, Davey MJ, Horne RS and Biggs SN (2016) Association between slow-wave activity, cognition and behaviour in children with sleep-disordered breathing. Sleep Med 25:49-55. 252 West AC, Martin BP, Andrews DA, Hogg SJ, Banerjee A, Grigoriadis G, Johnstone RW and Shortt J (2016) The SMAC mimetic, LCL-161, reduces survival in aggressive MYC-driven lymphoma while promoting susceptibility to endotoxic shock. Oncogenesis 5:e216. 253 Whitehead CL, McNamara H, Walker SP, Alexiadis M, Fuller P, Vickers DK, Hannan NJ, Hastie R, Tuohey L, Kaituâ&#x20AC;&#x2122;u-Lino TJ and Tong S (2016) Identifying late onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks gestation. Am J Obstet Gynecol 214:521-528. 254 Wijayarathna R and de Kretser DM (2016) Activins in reproductive biology and beyond. Hum Reprod Update 22:342-357. 255 Wilkinson D, Shepherd E and Wallace EM (2016) Melatonin for women in pregnancy for neuroprotection of the fetus. Cochrane Database Syst Rev 3:CD010527. 256 Winbanks CE, Murphy KT, Bernardo BC, Qian H, Liu Y, Sepulveda PV, Beyer C, Hagg A, Thomson RE, Chen JL, Walton KL, Loveland KL, McMullen JR, Rodgers BD, Harrison CA, Lynch GS and Gregorevic P (2016) Smad7 gene delivery prevents muscle wasting associated with cancer cachexia in mice. Sci Transl Med 8:348ra398. 257 Winship A, Menkhorst E, Van Sinderen M and Dimitriadis E (2016) Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer? Reprod Fertil Dev 28:395-405. 258 Winship AL, Rainczuk K and Dimitriadis E (2016) Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade. Cancer Invest 34:26-31. 259 Winship AL, Rainczuk K, Ton A and Dimitriadis E (2016) Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation. Oncol Lett 12:651-657.

262 Wong P, Polkinghorne K, Kerr PG, Doery JC, Gillespie MT, Larmour BI, Fuller PJ, Bowden DK and Milat F (2016) Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria. Bone 85:55-58. 263 Yang J and Young MJ (2016) Mineralocorticoid receptor antagonistspharmacodynamics and pharmacokinetic differences. Curr Opin Pharmacol 27:7885. 264 Yeap BB, Grossmann M, McLachlan RI, Handelsman DJ, Wittert GA, Conway AJ, Stuckey BG, Lording DW, Allan CA, Zajac JD and Burger HG (2016) Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Med J Aust 205:173-178. 265 Yeap BB, Grossmann M, McLachlan RI, Handelsman DJ, Wittert GA, Conway AJ, Stuckey BG, Lording DW, Allan CA, Zajac JD and Burger HG (2016) Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations. Med J Aust 205:228-231. 266 Yiallourou SR, Wallace EM, Miller SL and Horne RS (2016) Effects of intrauterine growth restriction on sleep and the cardiovascular system: The use of melatonin as a potential therapy? Sleep Med Rev 26:64-73.

Estrogenic effects of Ficus umbellata Vahl. (Moraceae) extracts and their ability to alleviate some menopausal symptoms induced by ovariectomy in Wistar rats. J Ethnopharmacol 179:332-344. 274 Zingue S, Tchoumtchoua J, Ntsa DM, Sandjo LP, Cisilotto J, Nde CB, Winter E, Awounfack CF, Ndinteh DT, Clyne C, Njamen D, Halabalaki M and CreczynskiPasa TB (2016) Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms. BMC Complement Altern Med 16:421.

EPUB AHEAD OF PRINT 1

Abell SK, Boyle JA, de Courten B, Soldatos G, Wallace EM, Zoungas S and Teede HJ (2016) Impact of type 2 diabetes, obesity and glycaemic control on pregnancy outcomes. Aust N Z J Obstet Gynaecol. DOI: 10.1111/ajo.12521

Au CC, Docanto MM, Zahid H, Raffaelli FM, Ferrero RL, Furness JB and Brown KA (2016) Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells. J Steroid Biochem Mol Biol. DOI:10.1016/j.jsbmb.2016.07.005

Bellofiore N, Ellery S, Mamrot J, Walker D, Temple-Smith P and Dickinson H (2016) First evidence of a menstruating rodent: the spiny mouse (Acomys cahirinus). Am J Obstet Gynecol. DOI: 10.1016/j. ajog.2016.07.041

Chan DW, Hui WW, Wang JJ, Yung MM, Hui LM, Qin Y, Liang RR, Leung TH, Xu D, Chan KK, Yao KM, Tsang BK and Ngan HY (2016) DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-beta/SMAD4 signaling. Oncogene. DOI:10.1038/onc.2016.307

Cumberland AL, Palliser HK, Walker DW and Hirst JJ (2016) Cerebellar changes in guinea pig offspring following suppression of neurosteroid synthesis during late gestation. Cerebellum. DOI:10.1007/ s12311-016-0802-0

Darbyshire P, McKenna L, Lee SF and East CE (2016) Taking a stand against predatory publishers. J Adv Nurs. DOI:10.1111/jan.13004

Deswaerte V, Ruwanpura SM and Jenkins BJ (2016) Transcriptional regulation of inflammasome-associated pattern recognition receptors, and the relevance to disease pathogenesis. Mol Immunol. DOI:10.1016/j.molimm.2016.09.023

Dubsky S, Zosky GR, Perks K, Samarage CR, Henon Y, Hooper SB and Fouras A (2016) Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge. J Appl Physiol. (1985). DOI:10.1152/japplphysiol.00476.2016

Funder JW (2016) Genetic disorders in primary aldosteronism-Familial and somatic. J Steroid Biochem Mol Biol. DOI:10.1016/j.jsbmb.2016.03.020

Galinsky R, Draghi V, Wassink G, Davidson JO, Drury PP, Lear CA, Gunn AJ and Bennet L (2016) Magnesium

267 Yim HC, Wang D, Yu L, White CL, Faber PW, Williams BR and Sadler AJ (2016) The kinase activity of PKR represses inflammasome activity. Cell Res 26:367379. 268 Yuan X, Wang W, Li J, Zheng P, Dong P, Chen L, Zhou Y, Xie G, Xu D, Liu Y and Shen L (2016) Gelsolin suppresses gastric cancer metastasis through inhibition of PKR-p38 signaling. Oncotarget 7:5345953470. 269 Zahid H, Simpson ER and Brown KA (2016) Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer. Curr Opin Pharmacol 31:90-96. 270 Zhou K, Motamed S, Thouas GA, Bernard CC, Li D, Parkington HC, Coleman HA, Finkelstein DI and Forsythe JS (2016) Graphene functionalized scaffolds reduce the inflammatory response and supports endogenous neuroblast migration when implanted in the adult brain. PLoS One 11:e0151589. 271 Zhu D, Muljadi R, Chan ST, Vosdoganes P, Lo C, Mockler JC, Wallace EM and Lim R (2016) Evaluating the impact of human amnion epithelial cells on angiogenesis. Stem Cells Int 2016:4565612.

260 Winship AL, Van Sinderen M, Donoghue J, Rainczuk K and Dimitriadis E (2016) Targeting Interleukin-11 receptor-alpha impairs human endometrial cancer cell proliferation and invasion in vitro and reduces tumour growth and metastasis in vivo. Mol Cancer Ther 15:720-730.

272 Zingue S, Cisilotto J, Tueche AB, Bishayee A, Mefegue FA, Sandjo LP, Magne Nde CB, Winter E, Michel T, Ndinteh DT, Awounfack CF, Silihe KK, Melachio Tanekou TT, Creczynski-Pasa TB and Njamen D (2016) Crateva adansonii DC, an African ethnomedicinal plant, exerts cytotoxicity in vitro and prevents experimental mammary tumorigenesis in vivo. J Ethnopharmacol 190:183-199.

261 Wong P, Fuller PJ, Gillespie MT and Milat F (2016) Bone disease in thalassemia: A molecular and clinical overview. Endocr Rev 37:320-346.

273 Zingue S, Michel T, Tchatchou J, Magne Nde CB, Winter E, Monchot A, Awounfack CF, Djiogue S, Clyne C, Fernandez X, Creczynski-Pasa TB and Njamen D (2016)

2016 ANNUAL REPORT / 65

sulfate reduces EEG activity but is not neuroprotective after asphyxia in preterm fetal sheep. J Cereb Blood Flow Metab. DOI:10.1177/0271678X16655548 11

Hooper SB, Crossley KJ, Zahra VA, van Vonderen J, Moxham A, Gill AW, Kluckow M, Te Pas AB, Wallace EM and Polglase GR (2016) Effect of body position and ventilation on umbilical artery and venous blood flows during delayed umbilical cord clamping in preterm lambs. Arch Dis Child Fetal Neonatal Ed. DOI:10.1136/ archdischild-2016-311159 Lang JA, Pearson JT, Binder-Heschl C, Wallace MJ, Siew ML, Kitchen MJ, Te Pas AB, Lewis RA, Polglase GR, Shirai M and Hooper SB (2016) Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth. J Physiol. DOI:10.1113/JP273682 Ling YH, Krishnan SM, Chan CT, Diep H, Ferens D, Chin-Dusting J, Kemp-Harper BK, Samuel CS, Hewitson TD, Latz E, Mansell A, Sobey CG and Drummond GR (2016) Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/ salt-induced hypertension. Pharmacol Res. DOI:10.1016/j.phrs.2016.12.015 McDonald R, Hodges R, Knight M, Teoh M, Edwards A, Neil P, Wallace EM and DeKoninck P (2016) Optimal interval between ultrasound scans for the detection of complications in monochorionic twins. Fetal Diagn Ther. DOI:10.1159/000448094 Mahony R, Gargan S, Roberts KL, Bourke N, Keating SE, Bowie AG, O’Farrelly C and Stevenson NJ (2016) A novel anti-viral role for STAT3 in IFN-alpha signalling responses. Cell Mol Life Sci. DOI:10.1007/ s00018-016-2435-3 Martino DJ, Ashley S, Koplin J, Ellis J, Saffery R, Dharmage SC, Gurrin L, Matheson MC, Kalb B, Marenholz I, Beyer K, Lee YA, Hong X, Wang X, Vukevic D, Motyer A, Leslie S, Allen KJ and Ferreira MA (2016) Genome-wide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1. Clin Exp Allergy. DOI:10.1111/cea.12863 Miller A, McLeod L, Alhayyani S, Szczepny A, Watkins DN, Chen W, Enriori P, Ferlin W, Ruwanpura S and Jenkins BJ (2016) Blockade of the IL-6 trans-signalling/ STAT3 axis suppresses cachexia in Krasinduced lung adenocarcinoma. Oncogene. DOI:10.1038/onc.2016.437 Moss TJ and Westover AJ (2016) Inflammation-induced preterm lung maturation: lessons from animal experimentation. Paediatr Respir Rev. DOI:10.1016/j.prrv.2016.10.004 Moussa YY, Tawfik SH, Haiba MM, Saad MI, Hanafi MY, Abdelkhalek TM, Oriquat GA and Kamel MA (2016) Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition. J Endocrinol Invest. DOI:10.1007/s40618016-0600-z

20 Murthi P, Davies-Tuck M, Lappas M, Singh H, Mockler J, Rahman R, Lim R, Leaw B, Doery J, Wallace EM and Ebeling PR (2016)

Maternal 25-hydroxyvitamin D is inversely correlated with fetal serotonin. Clin Endocrinol (Oxf). DOI:10.1111/cen.13281 21

Nakamura S, Walker DW and Wong FY (2016) Cerebral haemodynamic response to somatosensory stimulation in nearterm fetal sheep. J Physiol. DOI:10.1113/ JP273163

Nguyen VB, De Matteo R, Harding R, Stefanidis A, Polglase GR and Black MJ (2016) Experimentally induced preterm birth in sheep following a clinical course of antenatal betamethasone: Effects on growth and long-term survival. Reprod Sci. DOI:1177/1933719116681514

23 O’Brien CM, Chy HS, Zhou Q, Blumenfeld S, Lambshead JW, Liu X, Kie J, Capaldo BD, Chung TL, Adams TE, Phan T, Bentley JD, McKinstry WJ, Oliva K, McMurrick PJ, Wang YC, Rossello FJ, Lindeman GJ, Chen D, Jarde T, Clark AT, Abud HE, Visvader JE, Nefzger CM, Polo JM, Loring JF and Laslett AL (2016) New monoclonal antibodies to defined cell surface proteins on human pluripotent stem cells. Stem Cells. DOI:10.1002/stem.2558 24 Ong JD, Mansell A and Tate MD (2016) Hero turned villain: NLRP3 inflammasome-induced inflammation during influenza A virus infection. J Leukoc Biol. DOI:10.1189/jlb.4MR0616-288R 25 Pépin G, Nejad C, Thomas BJ, Ferrand J, McArthur K, Bardin PG, Williams BR and Gantier MP (2016) Activation of cGASdependent antiviral responses by DNA intercalating agents. Nucleic Acids Res. DOI:10.1093/nar/gkw878 26 Rudloff I, Cho SX, Lao JC, Ngo D, McKenzie M, Nold-Petry CA and Nold MF (2016) Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells. J Leukoc Biol. DOI:10.1189/ jlb.3MA0616-287R 27

Rudloff I, Cho SX, Bui CB, McLean C, Veldman A, Berger PJ, Nold MF and Nold-Petry CA (2016) Refining antiinflammatory therapy strategies for bronchopulmonary dysplasia. J Cell Mol Med. DOI:10.1111/jcmm.13044

28 Springhall E, Wallace EM, Stewart L, Knight M, Mockler JC and Davies-Tuck M (2016) Customised management of the third stage of labour. Aust N Z J Obstet Gynaecol. DOI:10.1111/ajo.12517 29 Sreenivasan R, Gordon CT, Benko S, de Iongh R, Bagheri-Fam S, Lyonnet S and Harley V (2016) Altered SOX9 genital tubercle enhancer region in hypospadias. J Steroid Biochem Mol Biol. DOI:10.1016/j. jsbmb.2016.10.009 30 Tan JL, Tan YZ, Muljadi R, Chan ST, Lau SN, Mockler JC, Wallace EM and Lim R (2016) Amnion epithelial cells promote lung repair via lipoxin A4. Stem Cells Transl Med. DOI:10.5966/sctm.2016-0077 31

Tham R, Vicendese D, Dharmage S, Hyndman RJ, Newbigin E, Lewis E, O’Sullivan M, Lowe AJ, Taylor P, Bardin P, Tang ML, Abramson MJ and Erbas B (2016) Associations between outdoor fungal spores and childhood and adolescent asthma hospitalisations. J Allergy Clin Immunol. DOI:10.1016/j. jaci.2016.06.046.

32 Tissera MS, Cowley D, Bogdanovic-Sakran N, Hutton ML, Lyras D, Kirkwood CD and Buttery JP (2016) Options for improving effectiveness of rotavirus vaccines in developing countries. Hum Vaccin Immunother. DOI:10.1080/21645515.201 6.1252493 33 Van Sinderen M, Oyanedel J, Menkhorst E, Cuman C, Rainczuk K, Winship A, Salamonsen L, Edgell T and Dimitriadis E (2016) Soluble Delta-like ligand 1 alters human endometrial epithelial cell adhesive capacity. Reprod Fertil Dev. DOI:10.1071/ RD15313 34 Vandeleur M, Walter LM, Armstrong DS, Robinson P, Nixon GM and Horne RS (2016) How well do children with cystic fibrosis sleep? An actigraphic and questionnaire-based study. J Pediatr. DOI:10.1016/j.jpeds.2016.11.069 35 Verbeek L, Zhao DP, Middeldorp JM, Oepkes D, Hooper SB, Te Pas AB and Lopriore E (2016) Haemoglobin discordances in twins: due to differences in timing of cord clamping? Arch Dis Child Fetal Neonatal Ed. DOI:10.1136/ archdischild-2016-311822 36 Wang Y, Li Y, Hyett J, da Silva Costa F and Nie G (2016) HtrA3 isoformspecific ELISAs for early detection of preeclampsia. J Biomol Screen. DOI:10.1177/1087057116682425 37 Wassink G, Davidson JO, Dhillon SK, Fraser M, Galinsky R, Bennet L and Gunn AJ (2016) Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep. J Cereb Blood Flow Metab. DOI:10.1177/0271678X16650455 38 Yawno T, Sabaretnam T, Li J, McDonald C, Lim R, Jenkin G, Wallace E and Miller S (2016) Human amnion epithelial cells protect against white matter brain injury after repeated endotoxin exposure in the preterm ovine fetus. Cell Transplant DOI:10.3727/096368916X693572 39 Yim C, Wong L, Cabalag C, Wallace EM and Davies-Tuck M (2016) Post-term surveillance and birth outcomes in South Asian-born compared with Australianborn women. J Perinatol. DOI:10.1038/ jp.2016.190.

66 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Technology platforms [ MHTP PLATFORM STRATEGIC INITIATIVES MANAGER: MS VIVIEN VASIC ]

Hudson Instituteâ&#x20AC;&#x2122;s pursuit of research excellence is underpinned by worldleading capabilities and expertise through our integrated network of Monash Health Translation Precinct (MHTP) technology platforms. These nine world-leading platforms are co-located on a central floor within the new $87.5 million Translational Research Facility, providing seamless interaction between research activities and clinical trials.

2016 ANNUAL REPORT / 67

Our world-leading technology platform facility supports scientists to pursue innovative approaches and advances in medical research by generating evidence and data. DNA

PROTEIN

CELL

TISSUE

ORGAN

INDIVIDUAL

POPULATION

MEDICAL GENOMICS

MASS SPECTROMETRY

FLOW CYTOMETRY

HISTOLOGY MICRO IMAGING

ANIMAL MODELS

CELL THERAPIES

BIOINFORMATICS BIOBANKING

Highlights Medical genomics During 2016, the medical genomics capability of the technology platform facility supported the processing of 10 675 Sanger sequencing results and 92 genomics projects, as well as 42 projects through our Fluidigm Single Cell Centre of Excellence. In addition, through our collaboration with Monash Health, medical genomics is supporting the lymphoma flagship project for the Melbourne Genomics Health Alliance (MGHA). MGHA is an alliance of 10 leading healthcare and research organisations that are assessing the use of medical genomics in the clinic. This project will investigate how sequencing genetic variants in lymphoma patients can help guide treatment. Funding provided in 2016 by our MHTP partner Monash University, enabled a $1 million advancement to next-generation sequencing instruments within the facility. The new equipment supports larger projects, such as the MGHA lymphoma project, and provides more rapid next-generation sequencing for both research and diagnosis.

Bioinformatics Bioinformatics links biology with computer science, statistics and applied mathematics to help interpret and understand biological data. Governance of the Australian node of the Human Variome Project (HVP) was transferred to Hudson Institute in 2016. Under the guidance of Professor Vincent Harley with support from the bioinformatics platform, the Australian node of the HVP will advance and develop capabilities for national data-sharing, to improve clinical genetic testing services and support medical research. The team also implemented two new bioinformatics pipelines to support analysis of the large sequencing data cohorts obtained from lymphoma patients as part of the MGHA partnership.

Histology The MHTP node of the Monash Histology Platform was officially opened in March, consolidating the provision of histological research services across our precinct. Histology is used by researchers to study the microscopic anatomy of

cells and tissues through staining techniques under light and electron microscopy. There are already 128 registered users of these new capabilities, with more than 1100 work requests and over 10 600 processing jobs completed by the node during the year.

Monash Micro Imaging In 2016, two new staff members joined the Monash microimaging platform: Dr Kirstin Elgass, Platform Manager and Dr Sarah Creed, Optical Microscopy Specialist, an expert in confocal, live cell and multiphoton microscopy techniques. Technologies used within the platform, including optical, fluorescence 4D and live cell microscopy, are critical to our understanding of cellular and molecular processes during both health and disease. Two new microscopes were installed within the facility this year. The addition of an Olympus FV1200 confocal microscope, a stereology system and two multiwell plate imaging systems will enable us to meet the increased needs of medical researchers conducting detailed analyses of cell and tissue structure and function.

68 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Launch of the Cell Therapies Platform and Miltenyi Biotec Cell Therapy Centre of Excellence [ CELL THERAPY AND REGENERATIVE MEDICINE: PROFESSOR GRAHAM JENKIN ]

2016 ANNUAL REPORT / 69

Launch of the Cell Therapies Platform “The new platform is a major initiative for our precinct, underpinning clinical translation of cell therapies and regenerative medicine,” said Professor Graham Jenkin, Head of the Cell Therapy and Regenerative Medicine research group in The Ritchie Centre. “We’ve built this platform in response to the undersupply of affordable clean room facilities in Victoria for clinical translation of our research, particularly for the manufacture of biologicals,” Prof Jenkin continued.

Centre of Excellence Miltenyi Biotec, manufacturer of the MACSQuant Tyto, granted the Cell Therapies Platform prestigious Early Adopter Program status for installation and support of the Miltenyi cell sorter. The company will also establish a Miltenyi Biotec Cell Therapy Centre of Excellence within the MHTP to assist and support translation of potential cell therapies to clinical trials.

Funding partners Therapeutic Innovation Australia, through the Translating Health Discovery Program of the Australian Government’s National Collaborative Research Infrastructure Strategy Program; Ian Potter Foundation; Miltenyi Biotec

“The Cell Therapies Platform will play a vital role in accelerating translational research leading to the development of new treatments for diseases such as bronchopulmonary dysplasia in premature newborns, cerebral palsy and cancer, and tissue replacement with biomimetic materials. “This will become a core facility of the Victorian Consortium for Cellbased Therapies and will underpin preclinical and early-phase clinical manufacture of tissues and cells for small- to medium-scale clinical trials and therapies.” Dr Gordon McPhee was appointed as Cell Therapies Platform Manager in mid-2016, bringing his expertise and experience in basic and translational

cell therapies research to the platform. The facilities available to scientists and commercial users at the Cell Therapies Platform are • The Biospherix Xvivo Good Manufacturing Practice Isolator, a modular clean room environment for human cell and tissue manipulation, expansion and growth, as well as GMP-compliant manufacture of medical devices • The MACSQuant Tyto, a GMPgrade cell sorter providing microfluidic chip-based human cell sorting for cell isolation for research and clinical trials • A GeSim Bioprinter for generation of 3D cell and tissue constructs.

70 / HUDSON INSTITUTE OF MEDICAL RESEARCH

MHTP research week 2016 The inaugural Monash Health Translation Precinct (MHTP) research week (21–25 November) showcased the excellent and diverse research from Hudson Institute and our precinct partners, Monash University and Monash Health. Covering a wide range of disciplines, the focus of the event was on innovative research areas, sharing knowledge and networking. The MHTP Translational Research Facility became a centre of activity as hundreds of leading researchers, clinicians, staff and students from across the precinct and all partner sites came together to celebrate the year’s research achievements. Researchers and clinicianscientists from multiple disciplines presented their work in three themes: ‘A healthy life span’; ‘Best of MHTP research’; and ‘Cell products and therapies’. Keynote speakers, CEO of the National Health and Medical Research Council (NHMRC), Professor Anne Kelso AO and Monash University Chancellor, Mr Simon McKeon AO, addressed standing-room-only audiences. An early career researchers session and a PhD student showcase symposium highlighted the work of our emerging researchers and PhD students.

Professor Anne Kelso

2016 ANNUAL REPORT / 71

Commercialisation and business development [ CHIEF COMMERCIALISATION OFFICER: MR ROB MERRIEL ]

Hudson Institute of Medical Research has a strong focus on taking research discoveries to the clinic through commercial partnerships. Our Commercialisation and Business Development Office works closely with researchers to assess intellectual property disclosures, establish partnerships with private and public sector companies, set up licensing for patented technology and attract industry funding for discovery projects. In 2016, Hudson Institute grew its intellectual property portfolio and signed significant deals with major pharmaceutical companies to take our research discoveries closer to patients.

2016 highlights Creating next-generation medicines: new industry collaboration announced This year, Hudson Institute and Monash University announced a collaboration with Switzerland-

based healthcare company Roche, to develop next-generation treatments for autoimmune diseases. The collaboration is based on research by Associate Professor Marcel Nold and Dr Claudia Nold, co-Heads of the Interventional Immunology in Neonatal Diseases research group in The Ritchie Centre, in conjunction with Professor James Whisstock and Dr Andrew Ellisdon from the Monash Biomedicine Discovery Institute. The multidisciplinary team is working with Roche to advance and translate their research, which focuses on turning proteins that target novel molecular pathways into new treatments. Based on their results, Roche has the option to exclusively licence the intellectual property in return for significant development and commercial milestone payments and royalties on product sales. A/Prof Nold’s work was supported by the philanthropic Fielding Innovation Award in 2016, which helps our scientists move their research to the commercial stage.

“This is a shining example of philanthropists, our community, medical researchers and the commercial sector working together to accelerate Australian innovation and advance the impact of discoveries in healthcare,” Chief Commercialisation Officer, Mr Rob Merriel said.

Exosomes, a commercial alternative to stem cell therapy In October, stem cell researcher Dr Rebecca Lim from The Ritchie Centre was invited, with Mr Merriel, to present her research on amniotic exosomes at the prestigious Stanford University BIO SPARK Showcase in San Francisco. The BIO SPARK event showcases science discoveries that are ready for partnering. Dr Lim presented a 15-minute pitch entitled, ‘Amniotic exosome therapy: a cell-free approach to regenerative medicine for fibrotic diseases’, to an audience of investors, venture capitalists and pharmaceutical companies.

72 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Exosomes are nanosized vesicles that contain ‘cargo’ such as proteins and nucleic acid material that are biologically active, and reflect the function of their parent cell. Amniotic exosomes are derived from the human placenta and released by amnion stem cells. Dr Lim’s research shows that these exosomes released by amnion stem cells could be what drives their regenerative qualities, and that they may have significant clinical potential in fibrotic diseases of the lung, heart and liver. Dr Lim says exosomes could be manufactured at a low cost and then freeze-dried, transported and administered to patients at the bedside more easily than traditional stem cell therapies. “Manufacturing stem cells at commercial quantities can be difficult and cost-prohibitive to take to the mass market. We hope to deliver a product that is a fraction of the cost.

ASCI Pharma Pty Ltd on a cancer biology project aiming to translate research discoveries into patient treatments.

creating the perfect environment in which an embryo can implant and form a pregnancy. “By making the endometrium more responsive to the embryo, we can hopefully work to improve success rates and offer hope to the hundreds of thousands of women undergoing IVF worldwide every year,” Dr Edgell said.

The partnership combines Hudson Institute’s specialist basic and clinical knowledge in cancer research and expertise in technologies, with Ariel University’s knowledge of peptide discovery screening, and research funding from ASCI Pharma Pty Ltd, which will also lead the commercialisation activities arising from the project.

Dr Edgell, a Research Fellow in the Centre for Reproductive Health, was announced as the 2017 Fielding Innovation Award recipient, which provides $50 000 to support studies to bring research a step closer to commercialisation.

The agreement reflects a strong focus on commercial and scientific partnerships that can propel basic research discoveries into tangible patient treatments.

International agreement to take cancer biology to the fore An international collaborative research agreement was entered into with Ariel University in Israel and

“A low-cost, exosome-based therapy could enable patients all over the world, including those in developing countries, to benefit from regenerative medicine,” said Dr Lim. “Hudson Institute is an attractive partner for venture capital as well as pharmaceutical and biotechnology companies. We have world-leading expertise in cell biology and ‘gold standard’ laboratory tools, plus the resources needed to take this discovery to the next level,” Mr Merriel said.

Finding could help improve IVF success rates Hudson Institute signed a research sponsorship and licence agreement with global pharmaceutical company Merck, to develop research by Dr Tracey Edgell into a test that may be able to predict a successful IVF outcome. Dr Edgell’s recent work has identified a panel of prognostic biomarkers for predicting the outcome of IVF treatment. Stemming from this research is Dr Edgell’s proposal that having a balance of the stimulating factor CSF3 and the receptor it attaches to within the uterus is essential to

2016 patent applications Patents filed, progressing and granted

2016

PHASE

2015

Intellectual property disclosures

Provisional patents lodged

Applications progressed to the international patent cooperation treaty stage

Progressed to national phase

Granted applications

Patent applications

2016 ANNUAL REPORT / 73

OUR PEOPLE

Early career researchers [ COMMITTEE CHAIR: DR COURTNEY MCDONALD ]

Early career researchers (ECRs) are researchers with less than 10 years experience, after receiving their PhD. The ECR committee promotes professional development and fosters a sense of community among ECRs, through various events and initiatives. The committee works closely with Monash Universityâ&#x20AC;&#x2122;s School of Clinical Sciences, providing support for all ECRs across our precinct.

ECRs mentorship program Mentoring is vital to the development of young scientists. The ECRs mentorship program pairs established scientists (mentors) with ECRs (mentees), based on their career objectives and challenges.

The first round of mentorships were completed in the first half of the year, with mentees rating the program on average, four out of five. A new round of mentorships are currently underway.

PhD mentoring program The transition from PhD student to postdoctoral researcher can be difficult to navigate. Based on the success of the ECR mentoring program, in 2016 the committee established a mentoring program for late-stage PhD students to help them navigate their journey into postdoctoral research. There was an outstanding uptake of this program, with 20 PhD students paired with 20 ECRs, providing one-on-one advice and professional development.

Each mentorship program runs for 12 months from July and can be continued informally after completion.

NHMRC funding review workshops

The program was a new initiative in July 2015; since commencing, 50 ECRs have taken part in the program.

In early 2016, the National Health and Medical Research Council (NHMRC) announced a structural

review of its grants program, which provides a vital source of funding for many career scientists, including ECRs. The committee hosted a workshop to update ECRs about proposed changes and provided an opportunity for them to contribute to an ECR specific submission on the structural review.

74 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Students [ 2016 HUDSON INSTITUTE STUDENT SOCIETY (HISS) ]

From left: Treasurer, Zoe Marks; Vice-President, Paulo Pinares Garcia; Creative Officer, Mikee Innocencio; President, Kimberley Dâ&#x20AC;&#x2122;Costa; Secretary, Harriet Fitzgerald

PHD AND HONOURS GRADUATES

The next generation of scientists Our large and vibrant student population includes 136 PhD students, 43 Honours students (including Bachelor of Science, Bachelor of Biomedical Sciences and Bachelor of Medical Science), 3 Masters students and 1 Doctor of Medicine. In 2016, 37 Honours students, 1 Masters student and 1 Doctor of Medicine student completed their degrees, while 12 PhD students completed their candidature and were awarded their doctorate.

183

STUDENTS

STUDENTS WITH MEDICAL TRAINING

Many of our students were published in prestigious scientific journals, including 75 students who were named first authors in journals such as Cancer Research, Cell Death and Disease, Nucleic Acids Research and Molecular Cancer Therapeutics. Publication enables our students to make an early mark in their chosen field of research from the beginning of their scientific careers, with the support of their supervisors. Our learning environment fosters excellence, innovation and collaboration, helping postgraduate research students to develop the confidence and tools they need to succeed in their careers.

STUDENT FIRST-AUTHOR PUBLICATIONS (23 % OF ALL INSTITUTE PUBLICATIONS)

Students at Hudson Institute are provided with one-on-one supervision and mentorship from research supervisors. They have access to a range of development opportunities, including workshops, seminars, and national and international conferences, plus scientific resources and state-ofthe-art technology platforms with which to conduct their research. Our students also have access to an onsite multidisciplinary hub of teaching through our precinct partner, Monash Universityâ&#x20AC;&#x2122;s School of Clinical Sciences at Monash Health.

2016 ANNUAL REPORT / 75

Three minute thesis competition More than 25 of our students competed in the Hudson Institute and School of Clinical Sciences final of the three minute thesis (3MT) competition, hosted by the Hudson Institute Student Society (HISS). 3MT celebrates research conducted by PhD students across Australia. It cultivates communication skills by challenging students to convey the significance of their research to

fellow students, scientists and staff, in just three minutes, while avoiding the use of scientific jargon. Dr Jonathan Dick (School of Clinical Sciences) and Dr Douglas Blank (The Ritchie Centre) won first and second place in the final respectively, and both went on to compete in the Faculty of Medicine, Nursing and Health Sciences final. Dr Blank was awarded first place at the faculty final, continuing to the Monash University competition, where he won the people’s choice award.

PhD student showcase symposium Six students from Hudson Institute were invited to present at the PhD student showcase symposium held as part of MHTP research week (November 21–25), based on the excellence of their research. Ms Zoe Marks, from our Centre for Innate Immunity and Infectious Diseases, was awarded both first prize and the people’s choice award for her presentation on novel type I interferon signalling in breast and ovarian cancer. HISS committee members coordinated the event and participated in a question and answer session with keynote speaker Professor Anne Kelso AO, CEO of the National Health and Medical Research Council.

Professional development sessions

3MT competition winners from left: Shreya Rana, Douglas Blank, William Berry, Gregory Ong, Kelli Sorby

Our students were given the opportunity to attend a wide variety of professional development sessions throughout 2016, including open forums, expert seminars, inductions, LabArchives training and mentoring breakfasts linking PhD students to clinicians.

76 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Hudson Institute Student Society 2016 HISS committee President: Kimberley D’Costa Vice-President: Paulo Pinares Garcia Secretary: Harriet Fitzgerald Treasurer: Zoe Marks Creative Officer: Mikee Innocencio HISS aims to create a positive environment for all students undertaking graduate research degrees, including Honours, Masters and PhD. Managed entirely by students and for students, HISS supports our next generation of scientists in their research degrees by offering mentoring, networking and social events, and by promoting a work– life balance. In 2016, HISS became a fully functional, independent, notfor-profit organisation with a registered ABN and bank account. HISS also received funding from the Monash Postgraduate Association to run social and mentoring events in 2016.

Events In June, HISS hosted a seminar in conjunction with Hudson Institute ECR committee, titled ‘What can you do with a PhD?’. The seminar demonstrated the range of career options available to PhD graduates beyond academia. Presenters included a media and communications professional, a pharmaceutical company representative, a secondary school teacher and a patent attorney, as well as scientists who have successfully navigated a more traditional journey as early career scientists. The primary aim of HISS is to support student connection and wellbeing throughout their studies. To achieve this, HISS hosts many social events, including an International Women’s Day barbecue to raise awareness of and funds for women’s health research, a games night, a ‘Hudson’s hidden Masterchef’ food competition, a student-focused Christmas party, and many ‘time out’ student lunches and morning and afternoon teas.

With increased visibility and a focus on student engagement, HISS began to engage students from related disciplines outside of Hudson Institute.

2016 graduates Congratulations to our 2016 graduates.

Higher degree by research students DOCTOR OF PHILOSOPHY Dr Dimuthu Alankarage Core sex determining gene, SOX9, regulates novel target genes during testis development. Prof Vincent Harley, Dr Rowena Lavery, Dr Pascal Bernard Dr Elizabeth Fletcher Mechanisms of mineralocorticoids receptormediated cardiovascular disease: a role for the peripheral molecular clock. Dr Morag Young, Prof Lea Delbridge Dr William Lee Is there bidirectional control of mitochondrial DNA replication? Prof Jus St. John, Dr Matthew McKenzie Dr Kieren Marini Mechanisms of platinum chemoresistance in lung cancer. Prof Neil Watkins, Dr Fernando Rossello Dr Anita Pinar The role of the inflammasome and interleukin-β in inflammatory disease. A/Prof Ashley Mansell, A/Prof Grant Drummond Dr Thilini Samarasinghe Effects of prenatal nicotine and inflammation on respiratory function and structure in the newborn. Dr Claudia Nold, Dr Mandar Joshi, A/Prof Philip Berger Dr Jimmy Shen Macrophage mineralocorticoid receptor regulates cardiac remodelling and blood pressure. Dr Morag Young, Prof Peter Fuller Dr Dhanya Sooraj ATF3 expression as a marker of response to histone deacetylase inhibition of bladder cancer progression. Prof Bryan Williams, Dr Dakang Xu Dr Rajini Sreenivasan Regulation of SOX9 in mammalian sex determination and differentiation. Prof Vincent Harley, A/Prof Robb de Longh Dr Jean Ling Tan Human amnion epithelial cells (hAECs) modulate immunological responses to mediate repair of lung injury. Dr Rebecca Lim, Prof Euan Wallace Dr Vijesh Vaghjani Functional characterisation of hepatocyte-like cells generated from human amniotic epithelial cells. Prof Jus St. John, Dr Ursula Manuelpillai

[ HEAD POSTGRADUATE RESEARCH STUDIES: PROFESSOR KATE LOVELAND ]

Dr Amy Winship The role of glycoprotein-130 cytokines in female reproduction and reproductive cancer. A/Prof Eva Dimitriadis

2016 ANNUAL REPORT / 77

DOCTOR OF MEDICINE Dr Muhammad Alamgeer Prognostic and predictive significance of the cancer stem cell markers in lung and breast cancers. Prof Neil Watkins, A/Prof Vinod Ganju MASTER OF PHILOSOPHY Ms Ann Dorothy Winter Modelling uterine fibroids. Prof Lois Salamonsen, Dr Jemma Evan

Honours students BACHELOR OF BIOMEDICAL SCIENCE (HONOURS) Ms Bianca Arena The long term consequences of intrauterine growth restriction and preterm birth on sleep quality in primary school aged children. Prof Rosemary Horne, Dr Stephanie Yiallourou Ms Karyssa Arendt Characterisation of Mitochondria Ubiquitin E3 Ligase 1 (MUL1) in the context of viral infection and inflammation using MUL1 LacZ transgenic mouse model. A/Prof Ashley Mansell, Dr Michelle Tate Ms Yan Yee Chan Does erythropoietin protect the brain from ventilation-induced brain injury? A dosage study. A/Prof Graeme Polglase Ms Fiona Gracey Genes that resensitize cancer cells to chemotherapy. Dr Andrew Stephens, Dr Maree Bilandzic, A/Prof Ron Firestein Ms Arielle Kogan Testing the therapeutic potential of human amniotic epithelial cells in a sheep model of asthma. Dr Rob Bischof, A/Prof Tim Moss Ms Mary Mansilla The function of a placenta-specific protease in trophoblast syncytialization. A/Prof Guiying Nie, Dr Sonia Teoh Ms Juliana Matti Identifying novel therapeutic targets for granulosa cell tumours (GCT). Dr Simon Chu, A/Prof Peter Fuller Ms Stephanie McLennan The effects of miRNAs on trophoblast cell function and embryo implantation. Dr Hong Nguyen, Prof Lois Salamonsen Ms Lara Rijkmans Neuropathology of the growth restricted spiny mouse foetus. Dr Hayley Dickinson, Dr Mary Tolcos, A/Prof David Walker

Mr Darren Tran The role of NOD1 signalling in the production of IL-33 by gastric epithelial cells in response to Helicobacter pylori infection. A/Prof Richard Ferrero, Dr Le Son Tran BACHELOR OF SCIENCE (HONOURS) Ms Gabriela Antoniotti Put down the chocolate! The impact of a high fat diet on uterine function. Dr Jemma Evans, Dr Renea Taylor Mr Brad Bassett Metastasis in ovarian tumors. Dr Andrew Stephens Ms Natalie Dasssanayake Sleep position and OSA. Prof Rosemary Horne Ms Indya Davies Transition at birth following lung hypoplasia. Prof Stuart Hooper, Dr Lauren Kerr Ms Heidi Fettke Investigation into the role of myc as a regulator of PD-L1 expression in high grade glioma. Prof Terrance Johns, Dr Daniel Gough Ms Tayla Hogan In vitro characterisation of p53 loss in ovarian cancer Dr Andrew Stephens, Dr Maree Bilandzic Mr Nicholas Johnson Role of the inflammatory microenvironment in development of colon cancer. Prof Bryan Williams, Dr Afsar Ahmed Ms Laura Moffitt Investigating the role of dipeptidyl peptidase IV in high-grade serous ovarian cancer Dr Andrew Stephens, Dr Maree Bilandzic Ms Anna Muccini Treatments that protect the structure and function in the developing brain. A/Prof David Walker Ms Merrin Pang Preterm immunity and cardiopulmonary disease. Dr Claudia Nold Ms Tayla Rose Penny Trading stem cells. Dr Courtney McDonald, Prof Graham Jenkin, Dr Suzie Miller Mr Krishan Singh Early life immunisation and cardiovascular disease. A/Prof Tim Moss, Prof David Burgner Ms Swati Swati Generation of molecular switches for muscle therapy. Dr Kelly Walton, A/Prof Craig Harrison Ms Madelynne White Elucidating the expression and regulation of human IFN-Îľ. Prof Paul Hertzog, Dr Nolliag Bourke

BACHELOR OF MEDICAL SCIENCE (HONOURS) Mr Aaron Bagnato The epithelial-mesenchymal transition and immunoevasiveness in breast carcinoma. Prof Bryan Williams Mr Joel Fernandez Does placental telomere length differ by maternal region of birth: a biological driver of increased adverse outcomes in South Asian born women. Prof Euan Wallace Mr Hugh Gao Loss of IFN-Îľ expression associated with poor prognosis in serous ovarian cancers with low immune cell infiltration. Prof Paul Hertzog Ms Sophie Hoy Reducing caesarean section: an in-depth analysis of the care of women undergoing induction of labour. Prof Euan Wallace Ms Hamid Didinny Izzaturrahmi Investigating Arg2 as a novel target of the IL10/MiR-155 signalling pathway in macrophages. Dr Claire McCoy Mr Aidan Kashyap Antenatal sildenafil to prevent pulmonary hypertension in congenital diaphragmatic hernia. Dr Kelly Crossley Ms Sophie Kinnear Uterine SOX17: a potential target for a novel, non-hormonal contraceptive. Dr Jemma Evans Ms Shagun Narula The role of TROP2 in trophoblast invasion. Dr Megan Wallace Ms Clare Nickson Impact of mineralocorticoid receptor antagonist therapy upon monocyte gene expression in cardiac failure. Dr Jun Yang Mr Benjamin Nowotny Developing a tool to predict medicolegal risk in obstetrics. Prof Euan Wallace Mr Samad Raza Induction of nuclear YAP by ERBB4 in high grade glioma. Prof Terrance Johns Ms Genevieve Shandler Impact of obstructive sleep apnoea in overweight/obese children on cardiovascular health. Prof Rosemary Horne Ms Sasha Skinner Partial amniotic carbon dioxide insufflation for fetoscopic spina bifida repair. Prof Graham Jenkin

78 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Gender equity [ COMMITTEE CHAIR: DR ASHLEY MANSELL ]

Hudson Institute recognises the challenges faced by women to progress their work and careers in biomedical research. While more than 70 per cent of our postdoctoral fellows are women, only 33 per cent of research group heads are women. There is still significant progress needed to address inequity across our institute and the biomedical sector. As a result, gender equity is a major strategic initiative that supports the future success of Hudson Institute. Only when women are advanced and developed to parity in senior positions can their experience and expertise be fully harnessed in the pursuit of scientific excellence. Formed in 2015, the Gender Equity Committee supports and encourages women and scientists with carer responsibilities to develop their careers, and identifies and addresses barriers that create disparity. Through these changes, we hope to see measurable advances in raising the profile, capacity and career advancement of women in the biomedical sector.

2016 highlights This year our journey towards gender equity took some major steps forward. A number of measures identified in the 2015 enterprise bargaining agreement to address gender equity were implemented, including increased flexibility in work hours, working at home policies, generous and flexible maternity leave entitlements and leave flexibility. These initiatives allow staff to tailor their work entitlements and environment to achieve success. A family-friendly workplace policy was adopted in 2016, recognising that staff have important roles outside the workplace. It contains the resources and options available to staff with carer responsibilities, including â&#x20AC;˘ Family-friendly scheduling of laboratory meetings and seminars based on school hours to provide staff the opportunity to fully engage in activities critical to their career and research â&#x20AC;˘ Assisting staff in locating and sourcing child-care opportunities.

The Hudson Institute Gender Equity Travel Award was established by the committee this year, to support conference participation by those with carer responsibilities. Attendance and participation at national and international conferences is crucial to progressing a scientific career. Conferences give scientists the opportunity to share and promote their research, meet other scientists working in their field and collaborate with peers to develop their work. The inability to travel to conferences is a significant block for scientists with caring responsibilities. The award provides financial support to a number of scientists each year to cover carer responsibilities while they attend a national or international meeting.

2016 ANNUAL REPORT / 79

2016 institute speakers HUDSON INSTITUTE SEMINAR SERIES Date

Topic

Speaker

31 March

Role and regulation of the epigenome during vertebrate development.

Prof Ryan Lister, The University of Western Australia

28 April

Sex, genes and human evolution.

Prof Jennifer Graves, La Trobe University

5 May

Deconstructing systems biology: Towards understanding and targeting the innate immune response in homeostasis and disease.

Prof Paul Hertzog, Hudson Institute of Medical Research

12 May

Molecular regulation of lymphoid cell response at barrier surfaces.

Prof Colby Zaph, Monash University

19 May

The assembly of bacterial surface structures.

Prof Trevor Lithgow, Monash University

26 May

Tackling HIV persistence: Tickle, shock or kill.

Prof Sharon Lewin, The Peter Doherty Institute for Infection and Immunity and The University of Melbourne

2 June

How to guide neurons and control metabolism.

A/Prof Roger Pocock, Monash University

9 June

Epilepsy genetics: The key to precision medicine.

Prof Ingrid Scheffer, The Florey Institute and The University of Melbourne

11 June

What genome wide association studies can tell us about the aetiology of breast cancer.

Prof Georgia Chenevix-Trench, QIMR Berghofer Medical Research Institute

17 June

Approaching an understanding of the complexity of STAT3 in oncogenesis.

Dr Daniel Gough, Hudson Institute of Medical Research

24 June

Unravelling the effects of intrauterine inflammation on lung development.

A/Prof Tim Moss, Hudson Institute of Medical Research

30 June

Fn14: A new player in cancer cachexia.

Prof Nick Hoogenraad AO, La Trobe University

7 July

Evaluating novel therapies for fibrosis.

A/Prof Chrishan Samuel, Monash University

14 July

Genes to big data and consequences for translation in eye disease.

Prof Paul Baird, The University of Melbourne

28 July

Estrogen and the male reproductive tract: Defining new roles in development and disease.

A/Prof Andrew Pask, University of Melbourne

4 August

RNA editing by ADAR1 suppresses innate immune sensing of endogenous RNA.

A/Prof Carl Walkley, St Vincent's Institute of Medical Research

18 August

Sex reversal in dragons: The rapid evolution of new sex determining modes.

Dr Clare Holleley, University of Canberra

1 September

Interventional immunology in diseases of the neonate.

Dr Claudia Nold, Hudson Institute of Medical Research

9 September

Osteocytes: The hidden cells that control strength and structure.

A/Prof Natalie Sims, St Vincent's Institute of Medical Research

15 September

Towards a vaccine for Tasmanian Devil Facial Tumour Disease.

Dr Bruce Lyons, University of Tasmania

18 September

Immune modulation by bacterial pathogens.

Dr Maria Kaparakis-Liaskos, Hudson Institute of Medical Research

22 September

Diet influences the frequency of Drosophila mtDNA haplotypes in laboratory population cages: The incomplete story.

Prof Bill Ballard, University of New South Wales

29 September

Glucocorticoids and fetal heart maturation implications for prematurity and fetal programming.

Prof Karen Chapman, University of Edinburgh, Scotland

6 October

TLR-mediated degradation of clAP1 triggers cell death and inflammasome activation in the absence of XIAP.

Dr Kate Lawlor, Walter and Eliza Hall Institute of Medical Research

13 October

Obesity, inflammation and the microbiome - partners in breast cancer risk.

Prof Evan Simpson, Monash University

20 October

Role of histone variant H3.3 in telomere maintenance and tumorigenesis.

A/Prof Lee Wong, Monash University

27 October

When the immune system is on (nucleic) acid.

Dr Michael Gantier, Hudson Institute of Medical Research

3 November

Inflammation control by neutrophil inflammasomes.

A/Prof Kate Schroder, University of Queensland

10 November

Characterisation of Innate-like T cells.

Dr Daniel Pellicci, The University of Melbourne

1 December

Muscle stem cell action during growth and regeneration.

Prof Peter Currie, Australian Regenerative Medicine Institute and Monash University

14 December

The new neuroendocrinology of human reproduction.

Prof Richard Anderson, University of Edinburgh, Scotland

80 / HUDSON INSTITUTE OF MEDICAL RESEARCH

CENTRE SEMINAR SERIES Date

Topic

Speaker

Centre

1 February

Targeting chemokine receptor CXCR4 in T cell acute lymphoblastic leukemia.

Dr Lauren Pitt, New York University School of Medicine, USA

CCR

11 February

Protein abundance-based and proteoform-specific insights into interactions between human respiratory syncytial virus and the host cell reveal pervasive antagonism of multiple antiviral pathways by nonstructural protein 1.

Prof Jeffrey Gorman, QIMR Berghofer Medical Research Institute and Proteomics Australia

CCR

18 February

Oestrogen and pulmonary hypertension - sex matters!

Prof Mandy MacLean, University of Glasgow, Scotland

CEM

1 February

Innate immune mechanism for viral dsRNA detection stories on RIG–I–like receptors.

A/Prof Sun Hur, Harvard Medical School, USA

CiiiD

1 March

Novel regulators of innate immune signalling.

Prof Endre Kiss-Toth, University of Sheffield, England

CiiiD

1 August

CD1-reactive T cells mediate human responses to tuberculosis infection.

Prof Branch Moody, Harvard Medical School and Brigham & Women's Hospital, USA

CiiiD

1 October

Translational funding.

Dr Ronnie Farquhar, Morningside Ventures

CiiiD

21 April

Can fertility be increased by manipulating gestational nutrition?

Dr Peter Smith, AgResearch and University of Otago, New Zealand

CRH

27 January

The sleeping brain and its developmental trajectory on infant cognition.

Dr Elaine Tham, Singapore Institute of Clinical Sciences, Singapore

TRC

10 June

Advances in regenerative medicine approaches for pulmonary diseases and critical illnesses.

Prof Daniel Weiss, University of Vermont, USA

TRC

15 June

Writing workshop.

Prof Kurt Albertine, University of Utah School of Medicine, USA

TRC

4 November

Improving outcomes for women with endometriosis.

A/Prof Louise Hull, The University of Adelaide

TRC

5 November

Creatine and pregnancy health symposium.

Prof Rod Snow, Deakin University

TRC

CENTRE FOR CANCER RESEARCH - 3RD COLLABORATIVE PAEDIATRIC CANCER RESEARCH DAY 29 JUNE 2016 Speaker

Affiliation

A/Prof Elizabeth Algar

Hudson Institute of Medical Research

Dr Jason Cain

Hudson Institute of Medical Research

Dr Jacqueline Donoghue

University of Melbourne

Prof Peter Downie

Children's Cancer Centre at Monash Health

A/Prof Paul Ekert

Maternal and Child Health Service and Murdoch Children’s Research Institute

Dr Jordan Handsford

Royal Children’s Hospital

A/Prof Meg Macy MD

University of Colorado and Children’s Hospital Colorado, USA

A/Prof Jeff Mann

Monash University

Dr Suresh Mathivanan

La Trobe University

Mr Todd Waugh

Monash Children's Hospital Paediatric Cancer Tissue Bank

Dr Christine White

Hudson Institute of Medical Research

A/Prof Lee Wong

Monash University

Dr Elise Young

Murdoch Children’s Research Institute

2016 ANNUAL REPORT / 81

THE RITCHIE CENTRE COLLOQUIUM - CELL THERAPY AND TRANSLATIONAL RESEARCH - 25-26 AUGUST 2016 Topic

Speaker

Affiliation

Cell therapy and regenerative medicine

Prof Tom Spurling

Swinburne University of Technology

Dr Shayanti Mukherjee

Hudson Institute of Medical Research

Dr Abhilasha Tiwari

Hudson Institute of Medical Research

Mr Michael Chae

Peninsula Health and Monash University

Dr Jurgen Schmitz

Miltenyi Biotec

Prof John Rasko

University of Sydney and Centenary Institute

Dr Annie McDougall

Hudson Institute of Medical Research

A/Prof Jerry Chan

Women's and Children's Hospital and Duke-NUS Medical School, Singapore

Dr Courtney McDonald

Hudson Institute of Medical Research

Dr Ina Rudloff

Hudson Institute of Medical Research

Prof David Gardner

University of Melbourne

A/Prof Eva Dimitriadis

Hudson Institute of Medical Research

A/Prof Caroline Gargett

Hudson Institute of Medical Research

Dr Miranda Davies-Tuck

Hudson Institute of Medical Research

A/Prof Marian Sturm

Cell and Tissue Therapies WA, Royal Perth Hospital

A/Prof Jerry Chan

Women's and Children's Hospital and Duke-NUS Medical School, Singapore

Dr Rebecca Lim

Hudson Institute of Medical Research

Prof Mark Kirkland

Cell Care Australia Pty Ltd

Prof John Rasko

University of Sydney and Centenary Institute

A/Prof Daniel Chambers

The Prince Charles Hospital

Prof William Sievert

Monash Health Translation Precinct Clinical Trials Centre

Prof Richard Macdonell

Austin Health

Prof Christine Wells

Melbourne Centre for Stem Cell Systems

Dr Shen Heazlewood

CSIRO

Dr Christian Nefzger

Australian Regenerative Medicine Institute and Monash University

Prof Justin Cooper-White

University of Queensland

Dr Jessica Frith

Monash University

Dr Dayalan Gunasegaram

CSIRO

Women's and children's health

Stem cells in paediatric clinical trials

Regenerative medicine

Biometrics and bioreactors

THE RITCHIE CENTRE PUBLIC FORUMS Date

Topic

Speaker

11 May 2016

Healthy sleep in school-aged children – the role of commercial sleep trackers: Good or bad?

A/Prof Hawley Montgomery-Downs, West Virginia University, USA A/Prof Margot Davey, Melbourne Children's Sleep Centre A/Prof Gillian Nixon, Melbourne Children's Sleep Centre Dr Sarah Biggs, Hudson Institute of Medical Research

25 August 2016

Stem Cell Therapies: Where are we now and where are we going?

A/Prof Daniel Chambers, The Prince Charles Hospital Prof Iona Novak, Cerebral Palsy Alliance Research Institute Prof John Rasko, University of Sydney and Centenary Institute Prof Richard Boyd, Cartherics Pty Ltd Dr Sherry Kothari, CRC for Cell Therapy Manufacturing (CTM) Dr Rebecca Lim, Hudson Institute of Medical Research Dr Susan Hawes, Australasian Society for Stem Cell Research

5 December 2016

The Ritchie Centre Kaarene Fitzgerald Public Forum - Stillbirth and Sudden Unexpected Death in Infancy Research Update.

Dr Rita Machaalani, University of Sydney and The Children’s Hospital at Westmead Dr Miranda Davies-Tuck, Hudson Institute of Medical Research Dr Emily Cohen, Hudson Institute of Medical Research

82 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Service to the scientific community MEMBERSHIP OF NATIONAL AND INTERNATIONAL BOARDS AND COMMITTEES Staff member

Committee, Council, Board, Foundation

Role

Dr Sarah Biggs

International Paediatric Sleep Association Board

Board Member

Australasian Sleep Association Board

Conference Chair

Dr Maree Bilandzic

Australasian Metastasis Research Society

Secretary

OZ Metastasis Research Society

Committee Member

Dr Kristy Brown

Victorian Cancer Biobank Board of Governance

Member

Victorian Cancer Biobank Consortium Committee

Member

Prof Henry Burger

Prof David de Kretser

Dr Jennifer Dowling

Victorian Cancer Biobank Scientific Advisory Committee

Duty Chair

Health& Medical Advisory Committee

Member

Pfizer Pharmaceuticals Advisory Board

Member

The Endocrine Society (USA) taskforce for clinical practice guideline on the management of primary aldosteronism

Chair

Academy of Technological Sciences and Engineering, Clunies Ross Awards Committee

Committee Member

Andrology Australia, Australian Centre of Excellence in Male Reproductive Health

Patron

Bertarelli Foundation Advisory Committee

Committee member

Biomedical Research Victoria

Director

BioMelbourne Network, Committee for Melbourne

Patron

Congress of Andrology Organising Committee

Committee Member

Doctors for the Environment

Committee Member

Faculty of 1000 Medicine, Diabetes & Endocrinology Evaluation Board

Member

Foundation 49 Men's Health

Committee Member

Human Variome Project International Ltd

Board Director

Infertility Treatment Authority of Victoria, Panel of Advisers, Clinical and Scientific Panel

Committee Member

International Academy of Human Reproduction

Fellow of the Society

Men's Health Policy Consultation

Ambassador

Minister's Male Health Policy Reference Group

Committee Member

Monash Comprehensive Cancer Consortium Management Committee

Member

Monash IVF Research and Education Foundation Advisory Board

Member

Monash Partners Academic Health Science Centre

Member

Monash Vision Bionic Eye Group

Advisory Board Chair

Paranta Biosciences

Board Director

Peter MacCallum Cancer Foundation's Governor's Circle

Committee Member

Southern Melbourne Integrated Cancer Service Joint Advisory Council

Member

Stem Cells Australia Governance Committee

Chair

Therapeutic Innovation Australia, Cell and Gene Therapy Committee

Committee Member

University of Queensland Centre for Clinical Research Advisory Board

Director

World Health Summit Advisory Committee

Member

World Health Summit Scientific Committee

Member

Victorian Infection and Immunity Network Organising Committee

Member

2016 ANNUAL REPORT / 83

Prof Jock Findlay

A/Prof Ron Firestein

Endocrine Society of Australia

Honorary Life Membership

NHMRC Genomics Targeted Call for Research Grant Advisory Committee

Committee Member

Robinson Research Institute Advisory Board

Chair

Society for the Study of Reproduction (USA)

Emeritus Member

Biogrid Australia Ltd

Member

Ms Harriet Fitzgerald

Society for Reproductive Biology (AUS/NZ)

Student Representative

Prof Peter Fuller

Academic Health Science Centre, Diabetes, Obesity, Men's Health and Endocrinology Theme

Committee Member

Cabrini Institute Board

Chair

NHMRC Venture Grants Committee

Deputy Chair

The Endocrine Society (USA) Publications Committee

Chair

Victorian Cancer Agency Consultative Council

Chair

Prof John Funder

A/Prof Vinod Ganju

Alan and Elizabeth Finkel Foundation

Director

Garnett Passe and Rodney Williams Memorial Research Foundation

Board Member

Grattan Institute

Director

Institute of Molecular Biosciences, University of Queensland, Scientific Advisory Board

Member

Obesity Australia

Executive Chair

Research Review, Sydney Adventist Hospital

Chair

Specialist Medical Review Council Executive Committee

Member

The Endocrine Society, Centenary Taskforce

Member

The Endocrine Society, International Outreach Taskforce

Member

Monash Oncology Research Institute

Member

A/Prof Caroline Gargett

National Stem Cell Foundation of Australia

Non-Executive Director

Prof Vincent Harley

Human Variome Project (Australian node)

National Director

Lorne Genome Conference Board Inc

President

Endocrine Society of Australia

Council Member and Assistant Treasurer

Paranta Biosciences

Scientific Advisor

Paranta Biosciences

Scientific Advisor

A/Prof Craig Harrison

A/Prof Mark Hedger Prof Paul Hertzog

Prof Rosemary Horne

Prof Brendan Jenkins

Prof Terrance Johns

Monash Health Translation Precinct Medical Genomics Committee

Co-convenor

State Government of Victoria, Platform Technologies Advisory Committee

Member

Victorian Infection and Immunity Network

Co-convenor

Victorian Infection and Immunity Network Industry Alliance

Co-convenor

Australasian Sleep Association, Research Committee

Member

International Paediatric Sleep Association Board

Executive Member and Board Member

International Society for the Study and Prevention of Infant Death, Physiology Working Group

Executive Member and Chairperson

SIDS and Kids National Scientific Advisory Group

Chair

Cancer Council Victoria, Standing Research Subcommittee

Member

International Cytokine and Interferon Society Council

Member

International Cytokine and Interferon Society, Meetings Committee

Member

Victorian Centre for Functional Genomics, Scientific Advisory Board

Member

The Cooperative Trials Group for Neuro-Oncology Management Committee

Member

The Cooperative Trials Group for Neuro-Oncology Scientific Advisory Council

Member

Dr Bryan Leaw

Australasian Society for Stem Cell Research, Junior Investigator Subcommittee

Member

Dr Joohyung Lee

Primetrics Pte Ltd Scientific Review Board

Member and Scientific Consultant

Dr Rebecca Lim

Australasian Society for Stem Cell Research, Policy, Ethics and Translation Subcommittee

Member

Prof Kate Loveland

American Society for Andrology Awards Committee

Member

Society for Reproductive Biology (AUS/NZ)

Fellow of the Society

Society for the Study of Reproduction (USA)

Member, Board of Directors

Women in Reproductive Science

Co-founder and Steering Committee Member

84 / HUDSON INSTITUTE OF MEDICAL RESEARCH

A/Prof Ashley Mansell

Prof Robert McLachlan

Immunology Group of Victoria

Committee Member

Victorian Infection and Immunity Network Executive Committee

Member

Andrology Australia

Director

Monash IVF Research and Education Foundation

Chairman

National Institute of Child Health and Human Development (USA), Data and Safety Monitoring Board

Member

Victorian Assisted Reproduction Treatment Authority

Scientific Advisor

World Health Organisation Expert Working Group: Infertility Guidelines

Member

World Health Organisation Research on Methods for the Regulation of Male Fertility

Member

Dr Sarah Meachem

Australian Society for Medical Research

President

Dr Ellen Menkhorst

Australian and New Zealand Placental Research Association Council

Committee Member

A/Prof Frances Milat

Australian and New Zealand Bone and Mineral Society Therapeutics Committee

Member

Endocrine Society of Australia

Clinical Chair

Dr Suzanne Miller

Fetal and Neonatal Physiological Society

Board Member

A/Prof Tim Moss

Fetal and Neonatal Physiological Society

Board Member

A/Prof Tim Moss

Perinatal Society of Australia and New Zealand, Victorian Subcommittee

Chair

Dr Claudia Nold

NHMRC Research Translation Faculty

Member

A/Prof Marcel Nold

NHMRC Research Translation Faculty

Member

A/Prof Graeme Polglase

INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) International Randomised Controlled Trial, Advisory Board

Member

Prof Lois Salamonsen

Australian Society of Reproductive Biology

Fellow of the Society, Honorary Life Membership

Prof Lois Salamonsen

Society for the Study of Reproduction (USA), Nominating Committee

Member

Prof Lois Salamonsen

Society for the Study of Reproduction (USA)

Emeritus Member

Prof Jus St. John

MitoStock

Director

Winston Foundation

Director

Dr Megan Wallace

NHMRC Research Translation Faculty

Member

Victorian Government Innovation Economy Advisory Board

Member

Prof Bryan Williams

Ms Heba Zahid

Biogrid Australia Ltd

Chair

EnGeneIC Ltd, Scientific Advisory Board

Scientific/Clinical Advisor

Healthier Lives (New Zealand), International Science Advisory Panel

Member

Hope Funds for Cancer Research (USA)

Member, Board of Trustees and Scientific Advisory Council

International Cytokine and Interferon Society, Nomination Committee

Member

International Cytokine and Interferon Society, Publications Committee

Chair

Malaghan Institute (New Zealand), Scientific Review Panel

Member

Monash Comprehensive Cancer Consortium Management Committee

Member

Monash Comprehensive Cancer Consortium Steering Committee

Member

Monash Partners Academic Health Science Centre

Council

Pacific Edge Diagnostics Singapore Pte Ltd

Board of Directors

Pacific Edge Ltd

Board of Directors

Pacific Edge Pty Ltd

Board of Directors

Premierâ&#x20AC;&#x2122;s Award for Health and Medical Research Selection Panel

Chair

Therapeutic Innovation Australia, Biopharmaceuticals Biomaterials and Medical Devices Advisory Committee

Chair

Saudi Student Association

Vice President

2016 ANNUAL REPORT / 85

MEMBERSHIP OF EDITORIAL BOARDS Staff member

Journal

Board position

Prof Philip Bardin

Respirology

Deputy Editor

Dr Kristy Brown

Frontiers in Endocrinology and Oncology

Editorial Board Member

Journal of Steroid Biochemistry and Molecular Biology

Editorial Board Member

Prof Henry Burger

Steroids

Editorial Board Member

Climacteric

Editorial Board Member

Current Trends in Endocrinology

Editorial Board Member

Endocrinology

Editorial Board Member

Gynecological Endocrinology

Editorial Board Member

Hypertension Research

Editorial Board Member

Journal of Steroid Biochemistry and Molecular Biology

Corresponding Editor

Menopause

Editorial Board Member

Physiological Reports

Editorial Board Member

Steroids

Editorial Board Member

Dr Simon Chu

Edorium Journal of Gynecology and Obstetrics

Editorial Board Member

A/Prof Colin Clyne

Journal of Steroid Biochemistry and Molecular Biology

Editorial Board Member

Nuclear Receptor Research

Editorial Board Member

Steroids

Editorial Board Member

Prof David de Kretser

Faculty of 1000

Member, Reproductive Endocrinology Section

Prof Peter Fuller

Cancer Medicine

Editorial Board Member

Endocrinology

Editorial Board Member

Expert Opinion on Investigational Drugs

Section Editor

Faculty of 1000

Faculty Member

Molecular Endocrinology

Editorial Board Member

Steroids

Editorial Board Member

Faculty of 1000

Associate Faculty Member, Editorial Board

MicroRNA

Regional Editor

Biology of Reproduction

Member, Editorial Advisory Board

Reproductive Sciences

Associate Editor, Asia/Pacific

Scientific Reports

Editorial Board Member, Stem Cells and Regenerative Medicine

Andrologia

Editorial Board Member

Journal of Reproductive Immunology

Guest Editor, special theme volume: 'Inflammation in Reproduction, Pregnancy and Development'

Journal of Sleep Research

Member, Editorial Advisory Board

Sleep

Member, Editorial Advisory Board

Sleep Medicine

Member, Editorial Advisory Board

Cytokine

Editorial Board Member

Dr Michael Gantier

A/Prof Caroline Gargett

A/Prof Mark Hedger

Prof Rosemary Horne

Prof Brendan Jenkins Dr Maria Kaparakis-Liaskos

PLoS One

Academic Editor

Dr Joohyung Lee

PLoS One

Editorial Board Member

Dr Rebecca Lim

Frontiers in Cellular Neuroscience

Research Topic Editor

Prof Kate Loveland

Andrologia

Associate Editor

Andrology

Associate Editor

Faculty of 1000

Member, Reproductive Endocrinology Section

Journal of Assisted Reproduction and Genetics

Editorial Board Member

Spermatogenesis

Editorial Board Member

Repropedia

Editorial Board Member

Dr Yogeshwar Makanji

86 / HUDSON INSTITUTE OF MEDICAL RESEARCH

A/Prof Ashley Mansell

Frontiers in Immunology - Molecular Innate Immunity

Editorial Board Member

Prof Robert McLachlan

Endotext

Associate Editor

Journal of Andrology

Associate Editor

A/Prof Tim Moss

Frontiers in Integrative Physiology

Member, Editorial Board and Advisory Committee

Frontiers in Neonatology

Member, Editorial Board and Advisory Committee

A/Prof Guiying Nie

Frontiers in Bioscience

Managing Editorial Board

Reproductive Biology and Endocrinology

Reviewing Board Member

Reproductive Sciences

Editorial Board Member

Dr Liza O'Donnell

Spermatogenesis

Editorial Board Member

Tissue Cell

Editorial Board Member

A/Prof Graeme Polglase

Frontiers in Paediatrics - Neonatology

Associate Editor

A/Prof David Robertson

Future Medicine - Women's Health

Editorial Advisory Board

Prof Lois Salamonsen

Reproduction, Fertility and Development

International Advisory Panel

Repropedia

Editorial Board Member

Dr Peter Stanton

Tissue Barriers

Editorial Board Member

Dr Michelle Tate

Journal of Virology

Editorial Board Member

Virology Journal

Associate Editor

Cytokine & Growth Factor Reviews

Editorial Board Member

Faculty of 1000

Member

Frontiers in Cancer Genetics

Editorial Board Member

Journal of Interferon and Cytokine Research

Editorial Board Member

Journal of Virology

Editor

Prof Bryan Williams

Viral Immunology

Editorial Board Member

Dr Dakang Xu

Clinical and Experimental Pharmacology and Physiology

Associate Editor

Dr Morag Young

Endocrinology

Editorial Board Member

Journal of Endocrinology

Senior Editor, Cardiovascular

Journal of Molecular Endocrinology

Receiving Editor

Journal of Steroid Biochemistry and Molecular Biology

Receiving Editor

2016 ANNUAL REPORT / 87

MEMBERSHIP OF CONFERENCE ORGANISING COMMITTEES Staff member

Conference

Location

Date

Role on committee

A/Prof Frances Milat

Medical Journal of Australia Continuing Professional Development Seminar in Endocrinology

Melbourne, VIC

February 2016

Clinical Co-ordinator

Dr Daniel Gough

Lorne Cancer Conference

Lorne, VIC

11-14 February 2016

Organiser

A/Prof Ashley Mansell

Lorne Infection and Immunity Conference

Lorne, VIC

17-19 February 2016

Conference Co-convenor

Prof Robert McLachlan

Young Men’s Health Stakeholder Forum

Canberra, ACT

3-4 March 2016

Director

A/Prof Vinod Ganju

Secondary Breast Cancer, Enhancing Multidisciplinary Care Conference

Glen Waverley, VIC

18-19 March 2016

Organiser

Dr Kristy Brown

ENDO2016 - Annual Scientific Meeting of the US Endocrine Society

Boston, MA, USA

1-4 April 2016

Annual Meeting Steering Committee Member

Yogeshwar Makanji

ENDO2016 - Annual Scientific Meeting of the US Endocrine Society

Boston, MA, USA

1-4 April 2016

Annual Meeting Steering Committee Member

Richard Ferrero

American Gastroenterological Association Digestive Disease Week

San Diego, CA, USA

21-25 May 2016

Chair, Abstract Review Panel

A/Prof Tim Moss

The Perinatal Society of Australia and New Zealand 20th Annual Congress

Townsville, QLD

22-25 May 2016

Conference Organising Committee

A/Prof Mark Hedger

Society for the Study of Reproduction (USA)

San Diego, CA, USA

16-20 July 2016

Program Committee Co-chair

Inflammation in Reproduction, Pregnancy and Development - Satellite Symposium to the International Congress of Immunology

Palm Cove, QLD

17-20 August 2016

Convenor

A/Prof Tim Moss

Inflammation in Reproduction, Pregnancy and Development - Satellite Symposium to the International Congress of Immunology

Palm Cove, QLD

17-20 August 2016

Conference Organising Committee

A/Prof Ashley Mansell

International Congress of Immunology

Melbourne, VIC

21-26 August 2016

Program Organising Committee Member

A/Prof Frances Milat

Endocrine Society of Australia Annual Scientific Meeting

Gold Coast, QLD

21-24 August 2016

Clinical Chair

Dr Patrick Western

Society for Reproductive Biology Annual Conference

Gold Coast, QLD

21-24 August 2016

Chair of Sponsorship Committee

A/Prof Caroline Gargett

The Ritchie Centre Colloquium

Clayton, VIC

25-26 August 2016

Conference Organising Committee

Prof Graham Jenkin

The Ritchie Centre Colloquium and Public Forum

Clayton, VIC

25-26 August 2016

Conference Organising Committee

Dr Rebecca Lim

The Ritchie Centre Colloquium and Public Forum

Clayton, VIC

25-26 August 2016

Conference Organising Committee

Dr Yennie Pham

The Ritchie Centre Colloquium and Public Forum

Clayton, VIC

25-26 August 2016

Conference Organising Committee

Prof Rosemary Horne

International Conference on Stillbirth, SIDS and Baby Survival

Montevideo, Uruguay

8-10 September 2016

Conference Committee Member

Dr Davina Dadley-Moore

Second Annual Brain Cancer Discovery Collaborative Conference

Sydney, NSW

14-15 September 2016

Co-convenor

Prof Terrance Johns

Second Annual Brain Cancer Discovery Collaborative Conference

Sydney, NSW

14-15 September 2016

Co-convenor

Dr Jennifer Dowling

Victorian Infection and Immunity Network Young Investigator Symposium

Melbourne, VIC

14 October 2016

Member

Prof Kate Loveland

Monash Health Translation Precinct Research Week

Clayton, VIC

21-25 November 2016

Organising Committee

Prof Lois Salamonsen

Monash Health Translation Precinct Research Week

Clayton, VIC

21-25 November 2016

Organising Committee

88 / HUDSON INSTITUTE OF MEDICAL RESEARCH

2016 ANNUAL REPORT / 89

Our community We share our research and discoveries with our community and the general public, to teach and inspire the next generation about the wonders of science, and give back to our supporters to reward their interest and investment in groundbreaking science.

In 2016, we held public forums on stem cells and fetal and neonatal health, hosted aspiring scientists at the institute, and our researchers joined their communities at forums and fundraising events.

The forum explored topics including current and potential stem cell treatments and trials, as well as the regulatory environment of this growing area, in which clinicians currently operate.

Public forums on sleep, stem cells and SIDS

Partnership with John Monash Science School

The Ritchie Centre hosted three public forums in 2016, engaging the public in fetal, neonatal and women’s health research on topics ranging from sleep apps to SIDS and stem cells.

DNA screening, sterile surgery and PhD career seminars were part of year 10 work experience at The Ritchie Centre.

A public forum in August on the topic ‘Stem cell therapies: where are we now and where are we heading?’ gave our community an opportunity to hear about and discuss cuttingedge developments in stem cell therapies. The forum was chaired by obstetrician and researcher Professor Euan Wallace, with a panel including stem cell pioneer Professor Alan Trounson and clinical haematologist Professor John Rasko from the University of Sydney.

The students, from John Monash Science School, had a taste of all aspects of life in the laboratory, including observing experiments and visiting sleep laboratories. Researchers from The Ritchie Centre also visited John Monash Science School to present careers seminars and ran a booth at the school’s careers expo. Postdoctoral researcher Dr Stacey Ellery and PhD student Mikee Innocencio presented to a group of around 100 students from years 10 to 12. “Science is not just about staring down a microscope, there is so much

more that you can do,” Mr Innocencio said. “Research is something we’re passionate about. I wanted to show the students what a science degree can lead to. It’s also a way of giving back to the community by encouraging increased participation in science and hopefully one day I’ll be working beside them.”

Professor Robert McLachlan receives Queen’s Birthday Honours Renowned Hudson Institute researcher, clinical andrologist and men’s health advocate Professor Robert McLachlan, was made a Member of the Order of Australia in the 2016 Queen’s Birthday Honours List for his service to medicine in the field of endocrinology, particularly to men’s reproductive health and to medical research. Prof McLachlan is a physicianscientist who has made significant contributions to translational research in men’s reproductive health.

90 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Head of our Centre for Endocrinology and Metabolism, Professor Peter Fuller, said that Prof McLachlan has been a significant influence on men’s health in Australia, not just as a clinician and researcher, but also in public advocacy. Prof McLachlan has a long history of linking basic research on the regulation of male fertility to clinical outcomes. This research has resulted in major contributions to methods of evaluating spermatogenesis, its endocrine regulation and to developing male hormonal contraception. “Prof McLachlan is Australia’s leading clinical andrologist and is internationally recognised for his work on men’s reproductive health. He is an enthusiastic and articulate advocate for community awareness of men’s health issues,” Prof Fuller said.

5000 people,” he added.

Endometriosis panel

“This was a great opportunity for students to see real research applications firsthand, and this will assist students with their future subject and career choices,” Kirstine Carter, Career Pathways Coordinator at John Monash Science School said.

Hudson Institute women’s health researchers joined a panel of experts at a public forum to share their research and discuss issues facing women with endometriosis.

Event organiser and scientist in the Centre for Innate Immunity and Infectious Diseases, Dr Jennifer Dowling, says Day of Immunology activities foster a greater appreciation of the importance of our immune system. “We hope that we can build students’ knowledge about the crucial role the immune system plays in helping us to understand and treat diseases, from lupus to Alzheimer’s disease and cancer.”

The forum, hosted by Endometriosis Australia, was part of a film screening of Endo What?, a feature-length documentary on endometriosis. Associate Professor Caroline Gargett and Dr Jemma Evans joined a clinician and surgeon after the film to field questions from the audience. A/Prof Gargett spoke about her research into endometrial mesenchymal stem cells, and their role in the disease, while Dr Evans spoke about the role of proteins and the potential for an early diagnostic test for endometriosis.

Day of Immunology discovery tour Students from John Monash Science School experienced the future of science during a discovery tour at Hudson Institute to celebrate the International Day of Immunology. The year 10 students went into the laboratory to determine the cause of a simulated disease outbreak and participated in activities such as using a UV light to learn how well they really wash their hands. The students also toured the Monash Health Translation Precinct Translational Research Facility and spoke with leading immunity researchers and PhD students about their work and careers. Professor Paul Hertzog, Head of the Centre for Innate Immunity and Infectious Diseases, says the immune system is crucial to both basic human health and fighting disease.

Breast cancer researcher offers community insight at NBCF event Dr Kristy Brown offered the community an insight into her research exploring the links between obesity and breast cancer during a Pink Ribbon Breakfast in the Yarra Ranges. A National Breast Cancer Foundation (NBCF)-funded researcher, Dr Brown was invited to speak at the event about her research into the role of obesity factors and other hormones in oestrogen-dependent breast cancer. Around 150 guests attended the annual event, hosted by long-time NBCF supporter Karen Webb. It has raised more than $135 000 in 10 years.

Dr Brown spoke about her personal connection to the disease through her aunt, a breast cancer survivor, and how her research into metabolic pathways could be translated into novel and less invasive breast cancer therapies. Funding from NBCF has also allowed Dr Brown to supervise a PhD student, Cherie Au, to undertake breast cancer research projects in her laboratory. “Not only have funds from NBCF enabled my laboratory to examine the links between obesity and breast cancer in the hope of finding new treatments, but they have also given a head start to the next generation of young researchers investigating the disease,” Dr Brown said.

“The immune system has relevance to everyday life, including the importance of immunisation, and the role of diet and our microbiome in maintaining a healthy immune system. “It’s an exciting area for future study and work in medicine, in research and in the biotechnology and pharmaceutical industries. Infection and immunity research and development is one of Victoria’s strengths, employing upwards of

Dr Kristy Brown and long-term NBCF supporter, Karen Webb.

2016 ANNUAL REPORT / 91

OUR SUPPORTERS

Fielding Foundation [ MR PETER FIELDING WITH DR REBECCA LIM ]

Fielding Fellowship and Innovation Award Melbourne businessperson and philanthropist, Mr Peter Fielding, made a life-changing $1 million donation in 2014 through his Fielding Foundation in support of our brightest researchersâ&#x20AC;&#x2122; work. This donation enabled the establishment of the Fielding Fellowship, which provides funding for an early- to mid-career researcher during a crucial stage of their career development. In addition, the Fielding Innovation Award was established to support a researcher to take an innovative research discovery to the commercial stage. These awards were announced in December, to provide support for some of our best researchers over the coming year.

Fielding Fellowship The Fielding Fellowship for 2017 was jointly awarded to two outstanding immunology researchers at Hudson Institute: Dr Niamh Mangan from

the Centre for Innate Immunity and Infectious Diseases and Associate Professor Marcel Nold from The Ritchie Centre. Dr Mangan is an emerging expert in the immunology of infection and inflammation, who seeks to understand the role of the mucosal immune system in disease. Dr Manganâ&#x20AC;&#x2122;s work focuses on interferon epsilon, an important naturally occurring cytokine in the female reproductive tract, and its clinical potential in infectious and inflammatory diseases and cancer.

Dr Niamh Mangan

A/Prof Nold is a neonatologist and paediatrician, who, alongside Dr Claudia Nold, is co-Head of the Interventional Immunology in Neonatal Diseases research group. A/Prof Nold is working to reduce the burden of inflammatory diseases, including chronic lung diseases affecting premature babies and necrotising enterocolitis, a devastating disease that causes the bowel tissue of newborn babies to die, which has a mortality rate of up to 65 per cent. Associate Professor Marcel Nold

92 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Fielding Innovation Award The Fielding Innovation Award for 2017 was awarded to Dr Tracey Edgell from the Centre for Reproductive Health, to help develop her discovery on stimulating factor CSF3 and its role in promoting fertility. This award is designed to bridge the widening funding gap facing young scientists who are working to take a research discovery from the laboratory to clinical trials and then to patients. Dr Edgell’s recent work, sponsored and licensed by global pharmaceutical company Merck, identified a panel of prognostic biomarkers that may predict the outcome of each round of IVF. She proposes that targeting CSF3 and its receptor within the uterus may improve success rates for IVF in Australia and around the world. “The Fielding Innovation Award will allow me to look at new ways to make the endometrium more responsive to the embryo, to hopefully improve success rates and offer hope to the hundreds of thousands of women undergoing IVF worldwide every year,” Dr Edgell said. “We are indebted to Mr Fielding for his foresight and commitment to groundbreaking medical research and to developing the rich potential of our brightest young scientists. On behalf of Hudson Institute, I thank Mr Fielding for his generous contribution to science,” said Hudson Institute Director, Professor Bryan Williams. For further enquiries about philanthropy, please contact Ms Kay Blandthorn on t: +61 3 8572 2701 or e: hudson.foundation@hudson.org.au

Dr Tracey Edgell

Leaps and bounds: achievements of our inaugural Fielding Foundation award recipients The inaugural Fielding Fellowship and Fielding Innovation Award recipients have significantly progressed their research discoveries to commercial partnerships and clinical trials, thanks to the funding support of Mr Fielding. Dr Rebecca Lim, the 2016 Fielding Fellowship recipient, progressed three major projects • Together with neonatologist Dr Atul Malhotra, she commenced a safety trial into the use of amnion stem cells in the treatment of a premature lung disease, bronchopulmonary dysplasia • In November, Dr Lim secured funding from the NHMRC to commence a clinical trial for end-stage liver disease using amnion cells, in conjunction with Professor William Sievert from Monash Health • Dr Lim was chosen to present her work on amniotic exosomes to venture capitalists at Stanford University’s BIO SPARK Showcase in San Francisco, which provides selected researchers opportunities to engage with industry. The work of 2016 Fielding Innovation Award recipient, A/Prof Nold, has led to a partnership between Hudson Institute, the Switzerland-based health company Roche and Monash University to translate their discoveries into next-generation treatments for autoimmune diseases.

2016 ANNUAL REPORT / 93

Julian’s story In June, we conducted a fundraising appeal focused on Julian, who is now a healthy 10-year-old boy, thanks to treatment he received for severe obstructive sleep apnoea at the Melbourne Children’s Sleep Centre. Julian is a happy and active child, who loves footy, soccer and computers. However, when he was at kindergarten, Julian was often irritable and exhausted. He also snored loudly, sweated a lot and made strange noises in his sleep. Sometimes, Julian even seemed to stop breathing. During the day, he was tired and grumpy. His mother Natalie was so worried that she took Julian to their family GP, who referred him to the Melbourne Children’s Sleep Centre. Here, Julian took part in an overnight diagnostic sleep study, conducted by world-leading researchers from

Hudson Institute’s The Ritchie Centre. The Melbourne Children’s Sleep Centre is Australia’s largest childhood sleep centre and is recognised internationally for the high quality of its life-changing research. At the sleep centre, Julian was diagnosed with severe obstructive sleep apnoea, a condition caused by enlarged tonsils or adenoids that block the airways during sleep, causing long pauses in breathing called apnoea. Our researchers have shown that children with obstructive sleep apnoea often have trouble concentrating at school, which may lead them to being disruptive in class. At just three years of age, Julian underwent surgery to help relieve his condition.

Three years after his surgery, Julian was a happy and healthy boy. His daytime behaviour and concentration had improved dramatically. He returned to the sleep centre for a second overnight study, which confirmed that his breathing during sleep had returned to normal. Almost 40 per cent of children have some type of problem with their sleep and many disorders like Julian’s go undiagnosed. The Melbourne Children’s Sleep Centre is working to help diagnose these children, and thanks to our generous donors, researchers at The Ritchie Centre are now pioneering important research into the long-term effects of this surgical treatment so they can help more children.

94 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Thank you to our supporters Hudson Institute of Medical Research is grateful for the gifts received from individuals, trusts, foundations and organisations during the year. We also acknowledge the support of the Victorian State Government through its Operational Infrastructure Support Program, and the Australian Government through its funding bodies, including the National Health and Medical Research Council. These valuable contributions assist the Hudson Institute to continue its important research.

FUNDING BODY

LEW Carty Charitable Fund

VicSuper

Alliance for Lupus Research (USA)

Lord Mayor’s Charitable Foundation

Victoria Prize for Science & Innovation

Andrea Joy Logan Trust Fund

Lung Cancer Research Foundation (USA)

Victorian Cancer Agency

Angior Family Foundation

Merck Serono Grant for Fertility Innovation (Germany)

Wilrene Pty Ltd

Australian Academy of Science and Japan Society for the Promotion of Science Australian Chinese Medical Association of Victoria Australian Communities Foundation Australian Lions Childhood Cancer Research Foundation Australian Mitochondrial Disease Foundation

Miltenyi Biotec Monash Comprehensive Cancer Consortium

Windemere Foundation Worldwide Cancer Research (UK) Zouki

Monash IVF Pty Ltd Monash Partners Academic Health Science Centre

INDIVIDUALS

Monash University

Mr Donald Abell

National Breast Cancer Foundation

Professor Henry Burger

Australian Nuclear Science and Technology Organisation

National Health and Medical Research Council

Professor Arthur Clark

Australian Pork Ltd

National Heart Foundation

Mr Andrew Cummins

Australian Research Council

National Institutes of Health (USA)

Mrs Joan Donaldson

Bailey’s Day

Osteoporosis Australia

Mrs Patricia Donges

Bethlehem Griffiths Research Foundation

Ovarian Cancer Research Foundation

Mr Greg and Mrs Robyn Eagle

Bill & Melinda Gates Foundation (USA)

P & M Harbig Holdings

Mrs Andrea Evans

Cancer Australia

Perpetual Trustees

Mr Peter Fielding

Cancer Council Victoria

Rebecca L Cooper Medical Research Foundation

Associate Professor Ron Firestein

Cerebral Palsy Alliance

Rivkin Center for Ovarian Cancer Research (USA)

Mr Peter Laver

Children’s Cancer Foundation

Robert Connor Dawes Foundation

Coopers Brewery Foundation

Rotary Club of Balwyn

Cure Brain Cancer Foundation

Royal Australasian College of Surgeons

Davies Collison Cave

Science and Industry Endowment Fund

Endocrine Society of Australia

SIDS and Kids

Estate of Robert Clarence Cummings

Sleep Research Society Foundation (USA)

Estate of Blair Campbell Ritchie

Society for the Study of Reproduction

European Society of Human Reproduction and Embryology

State Government of Victoria

CASS Foundation

Evans Family Foundation Ferring Research Institute, Ferring Pharmaceuticals (USA) Fielding Foundation Fluidigm Gandel Philanthropy

Stillbirth Foundation Australia Sylvia and Charles Viertel Charitable Foundation

Mrs Winifred Gould

Mr Rob Liddle Ms Margaret Lothian Mr Neville Marriott Mr Lance Matheson Mr Andrew McCallum Mr John Prescott Mr & Mrs Keith Richards Mrs Jill Ross-Perrier Professor Lois Salamonsen Mrs Janette Smith Mrs Jean Thomas

Telethon Kids Institute

Professor Bryan Williams

The Creswick Foundation

Mr Mark Williams

The Royal Australasian College of Physicians

Ms Denise Young

Harold Mitchell Foundation

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

H & K Johnson Family Foundation

Therapeutic Innovation Australia

Ian Potter Foundation

Uniting Church Adult Fellowship

Inner Wheel Australia

United States Department of Defense

Lettisier Foundation

veski (Victorian Endowment for Science Knowledge and Innovation)

2016 ANNUAL REPORT / 95

Cycling for vital equipment

For each of the past 11 years, a team of dedicated riders has cycled a challenging 520 km across the length of Victoria in 24 hours to raise funds for vital equipment used by our scientists. This year was no exception to the tradition. In April, a team of 11 riders cycled from Echuca to Port Fairy, with assistance from a support crew, for Hudson Instituteâ&#x20AC;&#x2122;s Ride for Research. The ride is part of the Murray to Moyne Cycle Relay, which raises funds for health services across Victoria. Thanks to the valiant efforts of the riders and their support crew, and the generosity of donors and our sponsors Davies Collison Cave, Zouki CafĂŠ and VicSuper, this year the Ride for Research raised $26 000 for new scientific equipment. Combined with a generous $25 000 grant received from the Rebecca L. Cooper Medical Research Foundation, these funds enabled

the purchase of a new Clariostar Multimodal Microplate Reader. This state-of-the-art piece of equipment includes eight different modes to detect almost any wavelength on the UV-visible range. Researchers across Hudson Institute can use the plate reader to discover new diagnostic tests and new treatments. Hudson Institute Director, Professor Bryan Williams, who volunteered as a support crew member, thanked all our valued donors, sponsors, supporters, riders and crew for their efforts in raising funds. Prof Williams also thanked Mr Andrew McCallum, who has been a driving force and supporter of the Ride for Research for the past 11 years.

Our supporters Davies Collison Cave, VicSuper, Zouki.

96 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Board of directors The directors of Hudson Institute of Medical Research Board, 31 December 2016

Dr Robert (Bob) Edgar BEcon (Hons), PhD (Ohio State), FAICD Appointed: April 2009 Dr Edgar has extensive experience in financial services, including 25 years at ANZ Bank where he retired as Deputy Chief Executive Officer in 2009. He is also a director on the boards of Djerriwarrh Securities, Linfox Armaguard Pty Ltd and Transurban Ltd. Special responsibilities: Board chair

Professor Warwick Anderson AM BS (Hons) UNE, PhD (Adelaide), DUniv (Adelaide), FAHA (Int), FRCPA (Hon), FAAHMS, DH (Newcastle)

Mr Nigel Garrard Ecomm, AICD, CA FAMI

Appointed: July 2015

Mr Garrard has been the Managing Director and CEO of Orora Limited since 2013 when it was listed on the Australian Stock Exchange. Since starting his career at KPMG, Mr Garrard has held a number of senior executive postings including the Managing Director of SPC Ardmona, Coca Cola Amatil’s food and service division, Chiquita Brands South Pacific Ltd, and Amcor Australasia and Packaging Distribution. He is the former Chairperson of the Australian Government’s National Food Industry Strategy Ltd and has been a director of a number of industry and not-for-profit organisations. Mr Garrard is a director of the Packaging Council of Australia.

Prof Anderson is the Secretary-General of the Human Frontier Science Program, which funds international cooperation in research into the complex mechanisms of living organisms. He was previously CEO of the National Health and Medical Research Council and has been a member of numerous international medical research bodies. Professor Anderson is a ViceChancellor’s Professorial Fellow at Monash University and has previously held academic and research positions at Monash University, Baker Medical Research Institute, University of Sydney and Harvard Medical School. He was made a Member of the Order of Australia in 2005. Prof Anderson’s research focuses on the renal causes of hypertension, including humoural, neural and vascular remodelling aspects, resulting in 170 peer-reviewed articles.

Appointed: March 2016

Special responsibilities: Chair, Hudson Foundation; Investment Committee member

Professor Christina Mitchell MBBS, PhD, FRACP Appointed: September 2011 Prof Mitchell is the Academic Vice-President and Dean of the Faculty of Medicine, Nursing and Health Sciences at Monash University. Prof Mitchell trained as a physician-scientist specialising in clinical haematology. In September 2011, she was promoted to the position of Dean. She was the first woman to be appointed Dean of Medicine in any of the group of eight universities in Australia. In March 2015, Prof Mitchell was inducted into the Victorian Honour Roll of Women for her leadership as the Dean. In April 2015, she received the Lemberg Medal, which is awarded annually to a distinguished biochemist in Australia. She is also a member of the Australian Academy of Health and Medical Sciences.

Professor Pauline Nestor BA(Hons), MPhil, DPhil Mr Andrew Leyden BComm Appointed: March 2016 Mr Leyden has been a Managing Director of Lazard Corporate Advisory and its predecessors since 2003. He has also worked for Credit Suisse Group, ANZ McCaughan Dyson and Arthur Andersen. Special responsibilities: Chair, Investment Committee; Hudson Foundation member

Appointed: November 2013 Prof Nestor is Vice-Provost (Research) at Monash University. Her previous appointments at Monash University have included Associate Dean (Research) in the Faculty of Arts, and Academic Adviser to the Office of the Deputy Vice-Chancellor (Research). A highly published expert in nineteenth-century English literature and culture, Prof Nestor completed a BA (Hons) at Melbourne University, before attending Oxford University as a Rhodes Scholar.

2016 ANNUAL REPORT / 97

Ms Zita Peach BSc, GAICD, FAMI

Ms Maria Trinci BA/BComm, CA

Mr Graeme Wise B.Ec (Monash), FAICD

Appointed: May 2016

Appointed: March 2015

Appointed: November 2013

Ms Peach has been the Principal of Zita Peach Business Development Services since 2015. She has also worked in senior leadership roles as Executive Vice-President and Managing Director of Fresenius Kabi, Vice-President of Business Development at CSL Limited and Commercial Director at Merck Sharp Dohme. Ms Peach has extensive experience in commercialising technologies, licensing, mergers and acquisitions. Ms Peach is a graduate of the Australian Institute of Company Directors and a Fellow of the Australian Marketing Institute. She is a director of Starpharma Holdings, Vision Eye Institute Limited, AirXpanders Inc, Monash IVF, Bionic Vision Technologies and Mt Buller, Mt Stirling Alpine Resorts Management Board.

Ms Trinci has worked with KPMG, specialising in financial services since 2000, and was admitted to the partnership in 2012. Ms Trinci is currently the engagement partner for ANZ. She has worked in the banking industry in London, Edinburgh, Glasgow and New York with clients including Mellon, Deutsche Bank and Citigroup. Ms Trinci is also a volunteer board member and pro bono audit provider. She is Deputy Chair of the Cancer Council Victoria board and chairs their Finance, Risk and Audit Committee. She is involved in a variety of community service groups including the Ovarian Cancer Research Foundation, Crime Stoppers, Gay and Lesbian Switchboard Victoria and the Committee for Melbourne â&#x20AC;&#x201C; Future Focus Group.

Mr Wise began his career in sales and marketing, including 15 years at Alcoa, based in both Australia and the United Kingdom. In 1981, he moved to retailing with Myer before founding Adidem Pty Ltd to build and operate the Australian branch of The Body Shop chain of retail stores. Mr Wise is now Chair of the Adidem Group, which comprises companies in property, publishing and water purification. Mr Wise is also involved in philanthropic activities as founder and patron of The Big Issue magazine and Chair of the Wise Foundation.

Special responsibilities: Chair, Intellectual Property and Commercialisation Committee

Special responsibilities: Chair, Finance and Audit Committee

Ms Jane Bell BEc, LLB, LLM (Lon), FAICD Appointed: March 2009 Departed: March 2016

Mr John Weste BSc, MBA Appointed: March 2009 Departed: March 2016

Ms Jennifer Joiner BEcon, CPA Appointed: March 2009 Departed: March 2016

98 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Board committees FINANCE AND AUDIT COMMITTEE This committee assists the board in internal control and compliance, accounting and financial reporting, and risk management processes of Hudson Institute.

BOARD OBSERVER

COMPANY SECRETARY

Professor Erwin Loh MBBS, LLB(Hons), MBA, MHSM, PhD, FAIM, FCMI, FAICD, FACLM, FCHSM, FRACMA

Mr Rob Merriel BA, Grad Dip (Psych), Grad Dip (Accounting), CPA

Appointed: May 2016

Appointed: May 2014

Prof Loh is Chief Medical Officer and Executive Director of Innovation, Patient Safety and Experience at Monash Health, Victoria’s largest health service. Prior to this he was the Deputy Chief Medical Officer at the Peter MacCallum Cancer Centre. He is a barrister and solicitor of the Supreme Court of Victoria and High Court of Australia. Prof Loh has a medical degree from the University of Melbourne and a law degree with honours from Monash University. He also has a Master of Business Administration, Master of Health Service Management and a PhD that examined doctors in senior hospital management. He is fellow of the Royal Australasian College of Medical Administrators, Australasian College of Health Service Management, Australian Institute of Company Directors and Australasian College of Legal Medicine.

Mr Merriel is a Certified Practicing Accountant with more than 35 years’ experience working in medical research (Baker IDI and Hudson Institute), healthcare (Melbourne Health and Southern Health) and commercial organisations (Pacific Dunlop and Deloitte Consulting). The current Chief Financial Officer and Chief Commercialisation Officer of Hudson Institute, Mr Merriel is a Director of MHRP Pty Ltd and was previously the director and company secretary of several biotechnology-focused companies, including BioGrid Australia, Biocomm, the Australian Technology Fund and Evivar.

Prof Loh is also on the board of MHRP Pty Ltd and the Australasian College of Legal Medicine (where he is also Vice-President). He has previously been on the board of the Australian Medical Association (Victoria), the Law Institute of Victoria and the Royal Australasian College of Medical Administrators. He is an adjunct Clinical Professor at Monash University where he teaches health law and health services management. He is the chair of the Victorian State Committee of the Royal Australasian College of Administrators. Prof Loh has spoken at local and international conferences, published articles and book chapters on health law and medical management, and supervises doctoral students.

Members: Ms Maria Trinci (Chair since 2015), Ms Carmel Mortell and Secretary Mr Rob Merriel. Hudson Institute’s CEO, Prof Bryan Williams, attends meetings of this board committee. INVESTMENT COMMITTEE This committee advises the board and director on the effectiveness of investment policies, and approves the engagement of investment managers and investment transactions. Members: Mr Andrew Leyden (Chair since November 2016), Mr Nigel Garrard (since November 2016) and Secretary Mr Rob Merriel. Hudson Institute’s Financial Accountant, Mrs Jessie Wo, attends meetings of this board committee. INTELLECTUAL PROPERTY AND COMMERCIALISATION COMMITTEE This committee advises the board and director on statutory requirements for corporate governance and commercialisation of Hudson Institute’s intellectual property and related issues. Members: Ms Zita Peach (Chair since August 2016), Mr Grant Fisher, Dr Michael Pannacio, Dr Andrew Gearing, Dr Rob Klupacs and Secretary Mr Rob Merriel. Hudson Institute’s CEO, Prof Bryan Williams, attends meetings of this board committee.

2016 ANNUAL REPORT / 99

Organisational structure BOARD OF DIRECTORS SCIENTIFIC ADVISORY COMMITTEE DIRECTOR Professor Bryan Williams

EXECUTIVE

Chief Operating Officer Mr Rod Wealands Chief Financial Officer Chief Commercialisation Officer Mr Rob Merriel Executive Officer Ms Ann Scott Associate Directors Professor Paul Hertzog Professor Peter Fuller

CENTRE HEADS

Centre for Cancer Research Head: Associate Professor Ron Firestein

Centre for Endocrinology and Metabolism Head: Professor Peter Fuller

Centre for Genetic Diseases Head: Professor Jus St. John

Centre for Innate Immunity and Infectious Diseases Head: Professor Paul Hertzog SCIENTIFIC SUPPORT GROUP Centre for Reproductive Health Head: Professor Lois Salamonsen

The Ritchie Centre Head: Professor Stuart Hooper

MANAGEMENT COMMITTEES Early Career Researcher Committee Gender Equity Committee Histology Advisory Committee Imaging Committee MHTP Genomics Advisory Committee MHTP Postgraduate Administration OHSE Committee Purchasing Committee Recruitment Committee Seminar Committee Social Club Committee EBA Committee Equipment Committee Hudson Institute Student Society Committee (HISS)

100 / HUDSON INSTITUTE OF MEDICAL RESEARCH

Financial snapshot INCOME

EXPENDITURE

Infrastructure Monash University 7%

Administration expenses 16%

Commercial research 7%

Scientific and laboratory 84%

Philanthropic grants 19% Victorian Government 6% Australian Government 53% Investment income 4% Other income 4%

REVENUE

PROPORTION

2016 ($)

2015 ($)

Australian Government

53%

22 389 405

24 959 532

Victorian Government*

2 672 867

2 351 561

Philanthropic grants

19%

8 225 532

7 328 738

Commercial research

2 819 941

2 626 143

Infrastructure Monash University

3 131 004

4 327 451

Other income

1 610 163

1 697 061

Investment income

1 625 163

823 495

42 474 076

44 113 981

Total

Expenditure Scientific and laboratory

84%

36 076 745

38 549 915

Administration expenses

16%

7 077 068

6 503 248

43 153 813

45 053 163

-679 737

-939 182

Total Total surplus *Includes the Operational Infrastructure Support Program

2016 ANNUAL REPORT / 101

102 / HUDSON INSTITUTE OF MEDICAL RESEARCH

27-31 Wright Street Clayton VIC 3168 Australia www.hudson.org.au

t: +61 3 8572 2700 e: info@hudson.org.au w: www.hudson.org.au