ProfessorJohn O'Sullivan

Inaugural Professor of Cardiometabolic Medicine, The University of Sydney
Director, HFpEF Program, and Clinical-Academic Cardiologist, Royal Prince Alfred Hospital

Chair, DECODE-HFpEF International Expert Consensus
Lead Principal Investigator, pEF-NAD, CardioNAD and pEF-EX Clinical Trials

Professor John O’Sullivan is an academic cardiologist and translational scientist. His work defines the cardiometabolic mechanisms of heart failure with preserved ejection fraction (HFpEF) and how to target them therapeutically.

Through the HFpEF Program at Royal Prince Alfred Hospital and his laboratory at the Charles Perkins Centre, University of Sydney, he leads a translational program built on a simple premise: HFpEF is not one disease but a set of mechanism-defined endotypes, each with its own biology and its own therapeutic lever. Using deep human phenotyping, biobanking and multi-omics, from invasively phenotyped patients to living human myocardium, the program defines these endotypes and the biomarkers that detect them, matching therapy to mechanism. It draws on tens of thousands of patients across multiple cardiac phenotypes, hundreds of invasive haemodynamic assessments, and a biobank built on tens of thousands of human heart tissue biopsies, including living myocardial slices and wedge preparations.

His group has identified biomarkers and therapeutic targets underpinning distinct HFpEF disease pathways. These discoveries have translated into patented diagnostic technologies, early-phase clinical trials, and regulatory engagement with the U.S. Food and Drug Administration. He contributed the biomarker recommendations to the 2023 Australian cardiovascular risk guidelines. He holds a Level 3 Future Leader Fellowship from the National Heart Foundation and is Lead Principal Investigator on three investigator-initiated randomised controlled trials in HFpEF: pEF-NAD, CardioNAD and pEF-EX.

He chairs DECODE-HFpEF, an international expert consensus on matching phenotype to therapy in HFpEF, with contributors across Argentina, Australia, China, Europe, Japan, Singapore and the United States.

He leads an emerging Asia-Pacific collaborative program in HFpEF with Duke-NUS Medical School, Singapore, and Xi’an Jiaotong University, China, focused on HFpEF in the young. HFpEF presents at a substantially younger age in Asian populations than in Western cohorts and remains poorly characterised in this group. The collaboration brings deeply phenotyped cohorts across the three centres together to define its mechanisms.

Professor O’Sullivan trained at Harvard University, the Broad Institute and Massachusetts General Hospital, and maintains active collaborations with groups at Harvard, Oxford and Cambridge. He is an invited Grand Rounds speaker at Royal Brompton and Harefield Hospitals, London, and serves as an assessor for the Medical Research Future Fund. He established Australia’s first dedicated Cardiometabolic Medicine program and leads its clinical trials portfolio.

He is founder of a clinical-stage spinout, developing cardiometabolic diagnostics, and advises biotechnology and pharmaceutical companies on cardiovascular therapeutics and the design of late-phase cardiovascular trials.

His central aim is to make HFpEF a tractable, phenotype-defined disease, and to open the door to precision therapies for patients with heart failure.

Opportunities

The program is growing and new team members are welcome.

It offers a selective research environment for strong medical students and higher degree candidates working at the interface of cardiometabolic biology and clinical translation. Projects sit within active phenotyping platforms and clinical trials. Trainees gain access to deeply characterised cohorts, advanced imaging and integrated biomarker datasets, with clear pathways to authorship and high-impact publication.

The team is highly collaborative, and trainees gain rigorous experience in study design, analytical methods and translational strategy. The program suits self-directed people aiming for careers in academic medicine, biotechnology or clinical leadership.

Enquiries are welcome. Please email a CV and a short note on what interests you about the program to john.osullivan@sydney.edu.au.