Suitability: BMedSci, PhD Project leader: Associate Professor Frances Milat e: fran.milat@hudson.org.au Project description: We are currently involved in a variety of projects aimed at improving health outcomes in patients with metabolic bone disorders and osteoporosis. These projects include the optimisation of bone health in adults with neurological disability, understanding osteoporosis in haemoglobinopathies, the evaluation and management of bone disorders in chronic kidney disease and the management of bone health in premature ovarian insufficiency. Projects are available in all of these areas.

Suitability: Masters by Research, PhD Project leaders: Dr Jun Yang; Dr Ben Clissold e: jun.yang@hudson.org.au Project description: Primary aldosteronism (PA) is the most common, and a potentially curable, cause of hypertension, estimated to affect 5-10% of all hypertensive patients. It leads to greater cardiovascular injury than hypertension alone. In particular, PA confers a 3-4 fold increase in the risk of stroke and atrial fibrillation compared to essential hypertension in blood pressure-matched patients. However, PA screening is not actively recommended in stroke/atrial fibrillation (AF) management guidelines. Given the potential health impact of diagnosing a potentially curable form of hypertension, and reducing the risk of stroke and AF, we seek to evaluate the prevalence of PA in patients presenting to Monash Health with either acute stroke or transient ischemic attack. This project has the potential to change management guidelines for hypertension in stroke patients and optimise the timely diagnosis of PA. Keywords: primary aldosteronism, stroke, TIA, hypertension, endocrine hypertension, aldosterone

Suitability: Masters by Research, PhD Project leader: Dr Jun Yang e: jun.yang@hudson.org.au Project description: Aboriginal patients experience a disproportionate burden of cardiovascular disease, with hypertension being a key modifiable risk factor. The prevalence of primary aldosteronism, as the most common and potentially curable secondary cause of hypertension in nonIndigenous populations, has never been explored in Indigenous populations. We will engage with Indigenous communities in Victoria to gauge their attitude towards hypertension diagnosis and treatment, and seek their input in exploring primary aldosteronism in their communities. Keywords: primary aldosteronism, hypertension, endocrine hypertension, Aboriginal patients, Indigenous health

Suitability: BMedSci, Masters by Research, PhD Project leaders: Dr Jun Yang; Associate Professor Gang Chen e: jun.yang@hudson.org.au Project description: Primary aldosteronism (PA) is the most common, and a potentially curable, cause of hypertension, estimated to affect 5-10% of all hypertensive patients. It leads to greater cardiovascular injury than hypertension alone. Studies have demonstrated the cost-effectiveness of screening patients with resistant hypertension for PA, but there are no economic modelling studies of screening newly diagnosed hypertensive patients. An early diagnosis is likely to be less complicated for a patient than long-standing disease, and offer greater benefit in reducing cardiovascular risk. However, without a formal cost analysis, hypertension screening guidelines will remain locked in the

past to the detriment of our community. This project will use the cost-utility analysis (CUA) approach to estimate the incremental costs and effectiveness of using aldosterone-renin ratio (ARR) to screen for PA in primary care versus no screening. The within-trial analysis will be extrapolated using a Markov model, consisting of health outcomes following screening procedures versus no screening, to capture the long-term cost. The quality of life and direct medical costs will be collected from a current trial. The estimates of the effect on long-term health outcomes, quality of life and costs (such as cost savings of cardiovascular events averted) will be made from a comprehensive literature review. Sensitivity analysis will be performed to evaluate the cost-effectiveness of ARR screening in all versus subgroups of hypertensive patients. The outcomes will directly influence policy. Keywords: primary aldosteronism, costeffectiveness, hypertension, endocrine hypertension, aldosterone, health economics

Suitability: Honours, BMedSci, Masters by Research, PhD Project leaders: Dr Jun Yang; Dr Morag Young e: jun.yang@hudson.org.au Project description: Whilst dichotomous thresholds are currently used to diagnose primary aldosteronism (PA), emerging data supports the concept of a continuum of aldosterone excess. A longitudinal cohort study showed that higher aldosterone in the setting of a suppressed renin level (392 of 850 normotensive patients) was significantly associated with the development of hypertension. A robust cellular marker of aldosterone excess that correlates strongly with clinical outcomes following mineralocorticoid receptor (MR) antagonist treatment or adrenalectomy will complement the aldosterone-renin ratio (ARR) and confirmatory tests in the diagnostic algorithm for PA. As peripheral blood monocytes highly express the MR, they represent an accessible MRresponsive tissue to study aldosterone-induced changes in gene transcription. A number of genes identified by previous students will be characterised in vitro using RT-PCR and cell culture to confirm a change in their expression in response to MR activation or antagonism. These may then be validated in larger patient cohorts as robust biomarkers of aldosterone excess and inappropriate MR activation. Keywords: primary aldosteronism, biomarker, hypertension, endocrine hypertension, aldosterone

Suitability: Masters by Research Project leader: Dr Jun Yang e: jun.yang@hudson.org.au Project description: Clinical registries play an important role in measuring healthcare delivery, supporting quality improvement and evaluating clinical outcomes, particularly in the long-term. There are no primary aldosteronism (PA) registries in Australia. This is in contrast to other countries which lead the research in PA, including China (CONPASS PA Study Group - 3 publications in leading endocrine journals in 2018), Japan (JPAS - 6), Taiwan (TAIPAI - 8) and Germany (German Conn’s Registry - 10). Based on our existing REDCap database, we will develop a multicentre registry to systematically collect comorbidities, diagnostic parameters and long-term outcomes of patients with PA, both in and outside of clinical trials. Keywords: primary aldosteronism, registry, hypertension, endocrine hypertension, aldosterone

Suitability: Honours, Masters by Research, PhD Project leader: Professor Peter Fuller e: peter.fuller@hudson.org.au Project description: The mineralocorticoid receptor (MR) is an important therapeutic target in cardiovascular disease. We have identified interactions of the receptor that differ between the physiological hormones, aldosterone, cortisol and progesterone. We also have access to novel therapeutic agents in development. Understanding these interactions and their structural basis will lead to the development of new therapeutic agents. The studies involve the use of yeast 2-hybrid

screens, transactivation assays, structural analysis, mutation detection, comparative biology and a series of unique transgenic mouse models in which the MR has been either mutated or removed (knocked-out). This work is also associated with our clinical program. Keywords: aldosterone, mineralocorticoid, receptor, adrenal