Accepting PhD Students

PhD projects

Evaluating the prevalence of primary aldosteronism in patients with stroke and/or atrial fibrillation
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 blood pressure-matched essential hypertensives. However, PA screening is not actively recommended in stroke/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.

Evaluating the cost-effectiveness of screening for PA in all vs subgroups of hypertensive patients
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 than in a patient with longstanding 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. In this project, you will use the cost-utility analysis (CUA) approach to estimates the incremental costs and effectiveness of using 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 effect on long-run health outcomes, QOL and costs (such as cost savings of cardiovascular events averted) will be estimated from a comprehensive literature review. Sensitivity analysis will be performed to evaluate the cost-effectiveness of ARR screening in all vs subgroups of hypertensive patients. The outcomes will directly influence policy.
Identification of novel transcriptomic markers of PA
Project description: Whilst dichotomous thresholds are currently used to diagnose 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 (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 MR antagonist treatment or adrenalectomy will complement the ARR and confirmatory tests in the diagnostic algorithm for PA. As peripheral blood monocytes highly express the MR, they represent an accessible MR-responsive 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.
Establish a national PA registry to enable comprehensive data collection and multidisciplinary website
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 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 multicenter registry to systematically collect comorbidities, diagnostic parameters and long-term outcomes of patients with PA, both in and outside of clinical trials.

20022023

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Personal profile

Biography

Dr Jun Yang is a Research Scientist within the Cardiovascular Endocrinology Group at Hudson Institute, a Consultant Endocrinologist at Monash Health and a Senior Postdoctoral Fellow in the School of Clinical Sciences at Monash University.

Since graduating with a MBBS (Hons, rank number 1) from Monash University, she has been actively involved in basic and clinical research as well as clinical practice.

She undertook PhD studies with Dr Morag Young, Dr Colin Clyne and Professor Peter Fuller at Prince Henry’s Institute of Medical Research, now Hudson Institute, from 2008-2013. Her PhD thesis, entitled ‘Mineralocorticoid receptors (MR): mechanisms of ligand- and tissue-specific activation’, identified and characterised novel coregulators of the MR using a novel phage display technique in addition to cell culture work and gene expression assays. This work identified four novel coregulators that interacted with the MR in a context-specific manner, and was published in the journal, Molecular Endocrinology.

Since completing her PhD, Dr Yang has continued to work on coregulator discovery. In particular, as the Cardiovascular Endocrinology group has shown that MR in macrophages is a key determinant of the macrophage proinflammatory state, she is working to identify macrophage-specific MR coregulators with the ultimate aim of developing a tissue-selective MR modulator that can alter the macrophage proinflammatory state without affecting epithelial MR activity. This would offer protection from cardiac fibrosis and failure without causing hyperkalemia.

In addition to laboratory-based research, Dr Yang established the Endocrine Hypertension Service at Monash Health and Hudson Institute with Prof Fuller. She developed the guidelines for the management of primary aldosteronism (PA), coordinated inter-disciplinary research between the Departments of Interventional Radiology, Pathology, Cardiology, Respiratory Medicine, and Endocrinology, and collaborated with research groups in Perth, China, Italy, the Netherlands and the USA.

Dr Yang’s PhD was supported by a NHMRC postgraduate scholarship and RACP Shields Research Entry scholarship.  She has subsequently secured continuous Post-Doctoral Fellowships and Project Grants in excess of half a million from the Endocrine Society of Australia, Royal Australasian College of Physicians, Heart Foundation, Council for High Blood Pressure Research Australia, CASS Foundation, Rebecca Cooper Foundation, Collier Charitable Foundation and Monash University.

Dr Yang has presented nationally (2 invited presentations, 12 orals, 6 posters) and internationally (5 invited presentations, 1 oral, 8 posters including 1 Presidential Poster Prize in 2011).  She was invited to chair sessions on aldosterone-related diseases at the ESA conference in 2016 and US ENDO conference in 2019.  She was awarded the Novartis Junior Scientist Award at the Endocrine Society of Australia's meeting in 2011, the society’s highest basic science award for an early career researcher; and won the Best Oral Presentation Award at the International Society of Hypertension meeting in 2019.

By developing a research program where  the research is embedded in clinical service and supported by a capable team of committed academics, clinicians and scientists, Dr Yang strives to enhance the culture of ‘bedside to bench, and vice versa’ translational medicine, and allow the integration of cutting edge science into day-to-day healthcare.

Research interests

A range of projects have stemmed from collaborations both nationally and internationally, including investigation of:

    Techniques to improve the success and accuracy of adrenal vein sampling

    Confirmatory tests that can accurately diagnose primary aldosteronism (PA) as well as predict the subtype of PA

    24-hour blood pressure parameters that can better characterise PA

    The relationship between obstructive sleep apnoea and PA;

    The prevalence of PA in patients newly diagnosed with hypertension

    Transcriptomic profiling of patient samples to identify biomarkers of PA.

In December 2018, Dr Yang formed the Primary Aldosteronism Centre of Excellence (PACE). PACE is built on existing collaborations and led by internationally respected clinician-scientists in PA-related research in Australia, including Prof Peter Fuller from Hudson Institute of Medical Research/Monash Health, Prof Michael Stowasser and Dr Martin Wolley from Queensland University, who have published extensively in the field and set the standards for PA management in Australia. PACE also has the support of world leaders in cardiovascular endocrinology, resistant hypertension research and cardiovascular epidemiology, Dr Morag Young (Hudson Institute), Prof Markus Schlaich (University of Western Australia), Prof Trevor Mori (University of Western Australia) and Prof Christopher Reid (Curtin University); prominent primary care health services researcher, Prof Grant Russell (Monash University); and a senior biostatistician, Dr StellaMay Gwini (Monash University/Barwon Health). This inter-disciplinary and trans-national collaboration will allow the team to optimise capacity in the field of PA research and address knowledge gaps using a systematic and evidence-based approach. Discovery science will be woven into the fabric of clinical practice where mechanisms from preclinical models and molecular pathology will be translated into improved patient care.

Supervision interests

Dr Yang supervised one Biomedical Science honours student (2016) and three Science honours students (2017-18) to completion.  She is currently supervising a clinician PhD student with one more to commence in 2019. She has also supervised and mentored medical students and registrars on many projects.  Their work have been presented at national and international conferences, with 3 manuscripts published, 3 manuscripts under preparation and 5 new projects in progress.  She is keen to support the career development of all junior clinician and science students who have an interest in endocrinology.

Clinical activities

Dr Yang’s research outcomes have transformed clinical practice by developing a focussed expertise in the area of primary aldosteronism and establishing a streamlined, evidence-based pathway for its care. At Monash Health, the number of patients diagnosed with PA has increased 20-fold over 7 years; the success rate of adrenal vein sampling (a technically challenging step in PA diagnosis) has increased from 40% in 2010 to >95% in 2019; and targeted treatment has led to reduced medication burden with improved BP in all diagnosed patients.

Community service

Dr Yang strives to engage with primary healthcare networks and general practitioners by delivering regular education seminars throughout Victoria and offering clinical support.  She has also engaged patients to develop consumer-focussed education materials and a website to inform those who may have a diagnosis of primary aldosteronism.  She led a team of volunteers at Monash Health to participate in May Measurement Month, a global initiative to measure the blood pressure of people around the world during the month of May.  The team enthusiastically recorded blood pressure on over 1000 participants!

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Education/Academic qualification

Molecular Biology and Medicine, PhD, MONASH UNIVERSITY

Award Date: 5 Feb 2013

Medicine, MBBS (Hon), MONASH UNIVERSITY

Award Date: 13 Nov 2001

External positions

Head, Endocrine Hypertension Service, Hudson Institute of Medical Research

Consultant Endocrinologist, Monash Health

Early Career Research Fellow, School of Clinical Sciences, Monash University

Research area keywords

  • Primary aldosteronism, hypertension, endocrine hypertension, mineralocorticoid receptor, cardiovascular disease

Network

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