Prof John O’Sullivan

MB BCh BAO, MMedSci, PhD, Cert. Biostat (Harvard), FRACP, FRCPI, FAHA


Prof John O’Sullivan

Prof John O’Sullivan

  • Professor of Cardiometabolic Medicine, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney
  • Clinical-Academic Cardiologist, Royal Prince Alfred Hospital
  • Director, Heart Failure Alliance
  • Director, HFpEF Clinic, Royal Prince Alfred Hospital
  • Professor of Medicine, TU Dresden, Germany

Professor John O’Sullivan is a Clinical-Academic Cardiologist specialising in Heart Failure. He is the inaugural Professor of Cardiometabolic Medicine at the University of Sydney and Department of Cardiology, Royal Prince Alfred Hospital.

He is a Level 2 NHF Future Leader Fellow, and co-Director of the HFpEF (“Stiff Heart Failure”) Clinic at RPAH. He is Director of the Heart Failure Alliance across SLHD and WSLHD, incorporating RPAH, Concord, Westmead, and Blacktown Hospitals. John is Lead Principal Investigator on two clinical trials in HFpEF: CardioNAD (ACTRN12622000340730) at RPAH, and pEFNAD (ACTRN12622000372785) across the Heart Failure Alliance, which are extensions of his discoveries in the laboratory. John is an international expert in heart failure bioenergetics, whose expertise is sought internationally by national grant bodies, in addition to medical and cardiac societies. John’s clinical practice at Central Sydney Cardiology focusses on Heart Failure and Early Prevention of Atherosclerotic Cardiovascular Disease (ASCVD). John’s discoveries have been translated to clinical biomarkers, Medicare Item Numbers, and new diagnostic assays.

John completed his medical and cardiology training in Ireland, the USA, and Australia, and spent 4 years on a postdoctoral fellowship at Massachusetts General Hospital, Harvard Medical School, and the Broad Institute of Harvard and MIT. After foundational clinical training in cardiology, subspecialising in Heart Failure, he undertook a PhD in cardiovascular physiology, and then postdoc specialist training in metabolomics, functional genomics, and bioenergetics. John’s PhD work was awarded with Young Investigator Awards at the Irish Cardiac Society, American College of Cardiology, and American Heart Association (separate projects). John’s postdoctoral work was recognised with another Young Investigator Award at the American Heart Association, a Harvard Medical School Tosteson Award, and an MGH Poster of Distinction Award.

John has established a bench-to-bedside Heart Failure program of research underpinned by the strong governance structure of his Heart Failure Alliance, incorporating murine models of heart failure, ex vivo Langendorff and Working Heart Cardiac Perfusion models, a human “beating heart slice” model, primary human cardiomyocytes, stable-isotope cardiac substrate tracing, a heart failure biopsy program, a transcardiac heart failure gradient program, and a HFpEF clinic. The Alliance has also incorporated a community and consumer advisory group, health economists, and commercial partnerships obtaining novel tool compounds with promising efficacy in heart failure. In addition to publishing in the most highly ranked biomedical journals, obtaining continuous competitive funding, John has a track record of commercialisation. In 2016 he discovered a novel biomarker (first entered in the Human Metabolome Database in 2017), that received a Medicare Item number and is routinely measured by NSW Health Pathology. John’s expertise has been sought by the Medical Research Councils of the EU, UK, Norway, and New Zealand, and he is a Member of the Novel Cardiovasular Risk Assessment Expert Subgroup reporting to the Australian Department of Health. John is committed to improving the lives of patients living with heart failure.

  • John has clinical and research interests in heart failure, particularly Heart Failure preserved Ejection Fraction (HFpEF), a type of heart failure that now accounts for more than half of all heart failure cases, but for which there are no treatments. He uses a range of tools to study this disease, including cardiac MRI. Employing new insights from his HFpEF research program, he aims to offer the most up-to-date, evidence-based therapeutic strategies to help patients with this disease.
  • John has a strong clinical interest in cardiometabolic disease: how unhealthy diet, overweight / obesity, and insulin resistance interact with cardiovascular disease, driving atherosclerosis and heart failure. He also studies the role of the microbiome in these diseases.
  • Cardiovascular prevention, particularly how to employ the latest evidence in dietary science and exercise to prevent and manage cardiovascular disease, is a core focus of John’s clinical interests.

Metabolite signatures of heart failure, sleep apnoea, their interaction, and outcomes in the community. Shashwati Dutta*, Desmond Li*, Andy Wang, Mark Ishak, Kristina Cook, Melissa Farnham, Hasthi Dissanayake, Peter Cistulli, Imre Hunyor, Renping Liu, Ian Wilcox, Yen Chin Koay, Jean Yang, Sean Lal, John F. O’Sullivan. ESC Heart Failure (accepted 12/09/2021)

Core Functional Nodes and Sex-Specific Pathways in Human Ischemic and Dilated Cardiomyopathy. Mengbo Li*, Benjamin L. Parker*, Evangeline Pearson, Benjamin Hunter, Jacob Cao, Yen Chin Koay, Oneka Guneratne, David E. James, Jean Yang, Sean Lal*, John F. O’Sullivan*. Nature Communications 2020 Jun 2;11(1):2843. PMID: 32487995. PMCID: PMC7266817.

hRUV: Hierarchical approach to removal of unwanted variation for large-scale metabolomics data Taiyun Kim^, Owen Tang^, Stephen T Vernon, Katharine A Kott, Yen Chin Koay, John Park, David James, Stuart M. Grieve, Terence P Speed, Pengyi Yang+, Gemma A Figtree+, John F. O’Sullivan+, Jean Yee Hwa Yang+. +joint senior authors Nature Communications 2, 4992 (2021).

Optimising the Discovery and Assessment of Therapeutic Targets in Heart Failure with preserved Ejection Fraction. Gabrielle Fusco-Allison, Desmond K. Li, Benjamin Hunter, Dan Jackson, Paul G. Bannon, Sean Lal, John F. O’Sullivan. ESC Heart Failure 2021 Aug 2. doi: 10.1002/ehf2.13504. PMID: 34342166

Impact of dietary carbohydrate type and protein–carbohydrate interaction on metabolic health. Jibran A. Wali, Annabelle J. Milner, Alison W. S. Luk, Tamara J. Pulpitel, Tim Dodgson, Harrison J. W. Facey, Devin Wahl, Melkam A. Kebede, Alistair M. Senior, Mitchell A. Sullivan, Amanda E. Brandon, Belinda Yau, Glen P. Lockwood, Yen Chin Koay, Rosilene Ribeiro, Samantha M. Solon-Biet, Kim S. Bell-Anderson, John F. O’Sullivan, Laurence Macia, Josephine M. Forbes, Gregory J. Cooney, Victoria C. Cogger, Andrew Holmes, David Raubenheimer, David G. Le Couteur & Stephen J. Simpson Nature Metabolism, 3, 810–828 (2021)

Nutritional and metabolic regulation of the metabolite Dimethylguanidino Valeric Acid – an early marker of cardiometabolic disease. Jibran A. Wali*, Yen Chin Koay*, Jason Chami, Courtney Wood, Roman Rodionov, Andreas Birkenfeld, Dorit Samocha-Bonet, Stephen J. Simpson, John F. O’Sullivan. AJP – Endocrinology and Metabolism. PMID: 32663097; PMCID: PMC7509244.

Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms. Jibran A. Wali, Natalia Jarzebska, David Rubenheimer, Stephen J. Simpson, Roman Rodionov, John F. O’Sullivan. Nutrients. 2020 May; 12(5): 1505. PMCID: PMC7284903. PMID: 32455838.

Disulfiram Treatment Normalizes Body Weight in Obese Mice. Michel Bernier, Sarah J. Mitchell, Devin Wahl, Antonio Diaz, Abhishek Singh, Wonhyo Seo, Mingy Wang, Ahmed Ali, Tamzin Kaiser, Nathan L. Price, Miguel A. Aon, Eun-Young Kim, Michael A. Petr, Huan Cai, Alessa Warren, Clara Di Germanio, Andrea Di Francesco, Ken Fishbein, Vince Guiterrez, Dylan Harney, Yen Chin Koay, John Mach, Ignacio Navas Enamorado, Tamara Pulpitel, Yushi Wang, Jing Zhang, Li Zhang, Richard G. Spencer, Kevin G. Becker, Josephine M. Egan, Edward G. Lakatta, John O’Sullivan, Mark Larance, David G. LeCouteur, Victoria C. Cogger, Bin Gao, Carlos Fernandez-Hernando, Ana Maria Cuervo, Rafael de Cabo. Cell Metabolism, 2020 PMID: 32413333

Plasma Levels of TMAO can be Increased with ‘Healthy’ and ‘Unhealthy’ Diets and Do Not Correlate with the Extent of Atherosclerosis but with Plaque Instability. Yen Chin Koay#, Yung-Chih Chen#, Jibran A. Wali, Alison W. S. Luk, Mengbo Li, Hemavarni Doma, Rosa Reimark, Habteab T. Habtom, Ashley E. Frank, Gabrielle Fusco-Allison, Jean Yang, Andrew Holmes, Stephen J. Simpson, Karlheinz Peter, John F. O’Sullivan. Cardiovasc Res. 2021 Jan 21;117(2):435-449. pii: cvaa094. doi: 10.1093/cvr/cvaa094. PMID: 32267921

Effect of chronic exercise in healthy young male adults: a metabolomic analysis. Yen Chin Koay, Kelly Stanton, Vivian Kienzle, Mengbo Li, Jean Yang, David S. Celermajer, John F. O’Sullivan. Cardiovasc Res. 2021 Jan 21;117(2):613-622. pii: cvaa051. doi: 10.1093/cvr/cvaa051. PMID: 32239128

Systems Proteomics of the Intermittent Fasting Response Identifies an Unexpected Role for HNF4α Luke Hatchwell, Dylan J. Harney, Michelle Cielesh, Kieren Young, Yen Chin Koay, John F. O’Sullivan, Mark Larance. Cell Rep. 2020 Mar 10;30(10):3566-3582.e4. doi: 10.1016/j.celrep.2020.02.051. PMID: 32160557

Ingestion of resistant starch by mice markedly increases microbiome-derived metabolites. Yen Chin Koay*, Jibran A. Wali*, Alison W. S. Luk, Laurence Macia, Victoria C. Cogger, Tamara J. Pulpitel, Devin Wahl, Samantha M. Solon-Biet, Andrew Holmes, Stephen J. Simpson, John F. O’Sullivan. FASEB J 2019. Mar 29:fj201900177R. doi: 10.1096/fj.201900177R. PMID: 30925066.

Myocardial Metabolic Perturbations in Advanced Ischemic and Non-Ischemic Dilated Human Heart Failure. Jacob Cao, Yen Chin Koay, Lake-Ee Quek, Benjamin Parker, Sean Lal*, John F. O’Sullivan*European Journal of Heart Failure, 2019 Aug;21(8):1042-1045. doi: 10.1002/ejhf.1479. Epub 2019 Jun 11. PMID: 31184404.

Ingestion of resistant starch by mice markedly increases microbiome-derived metabolites. Yen Chin Koay*, Jibran A. Wali*, Alison W. S. Luk, Laurence Macia, Victoria C. Cogger, Tamara J. Pulpitel, Devin Wahl, Samantha M. Solon-Biet, Andrew Holmes, Stephen J. Simpson, John F. O’SullivanFASEB J 2019. Mar 29:fj201900177R. doi: 10.1096/fj.201900177R. PMID: 30925066.

Metabolites downstream of predicted loss-of-function variants inform relationship to disease. Mengbo Li, Andy Wang, Lake-Ee Quek, Stephen Vernon, Gemma A. Figtree, Jean Yang, John F. O’SullivanMol Genetics and Metab ( (Epub ahead of print).

MiRNA93-5p is a Novel Predictor of Coronary Artery Instent Restenosis. John F. O’Sullivan, Antoinette Neylon, Eoin F. Fahey, Pengyi Yang, Catherine McGorrian, Gavin J. Blake. Heart Asia. 2019 Feb 22;11(1):e011134. doi: 10.1136/heartasia-2018-011134. eCollection 2019. PMID: 31031831.

Branched chain amino acids impact health and lifespan indirectly via diet balance and appetite control. Samantha M Solon-Biet, Victoria C Cogger, Tamara Pulpitel, Devin Wahl, Ximonie Clark, Alistair Senior, Qiaoping Wang, Amanda Brandon, Ruth Perks, John F. O’Sullivan, Yen C Koay, Kim Bell-Anderson, Melkam Kebede, Belinda Yau, Clare Atkinson, Gunbjorg Svineng, Rosilene Waern, Jibran A Wali, Matthew D Piper, Robert Cumming Vasant Hirani, David J Handelsman, Paula Juricic, Linda Partridge, David Raubenheimer, Gregory Cooney, David G Le Couteur , Stephen J Simpson. Nature Metabolism, volume 1, pages532–545 (2019).

Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes. John F O’Sullivan, Jordan E Morningstar, Baohui Zheng, Sarah Jeanfavre, Justin Scot, Qiong Yang, Celine Fernandez, Ramachandran S. Vasan, Michelle T. Long, Olle Melander, Thomas J. Wang, Caroline Fox, Randall T. Peterson, Clary Clish, Kathleen Corey, Robert E. Gerszten. J Clin Invest. 2017 Dec 1;127(12):4394-4402. PMID: 29083323.

Metabolite Profiles and the Risk of Cardiometabolic Disease. O’Sullivan J, Gerszten RE Eur Heart J 2014; 35; 2197–2204. DOI: 10.1093/eurheartj/ehu270.

Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease. Curtis R. Warren, John F. O’Sullivan, Max Friesen, Caroline E. Becker, Xiaoling Zhang, Yoshi Wakabayashi, Jordan E. Morningstar, Xu Shi, Jihoon Choi, Fang Xia, Mary H. C. Florido, Jennifer Shay, Derek T. Peters, Kiran Musunuru, Sekar Kathiresan, Laurence Daheron, Jun Zhu, Robert E. Gerszten, Rahul Deo, Vasan Ramachandran, Christopher J. O’Donnell, and Chad A. Cowan. Cell Stem Cell 2017 Apr 6;20(4):547-557. PMID: 28388431.

Metabolite Profiling Identifies Anandamide as a Biomarker of Nonalcoholic Steatohepatitis. Taylor Kimberly, John O’Sullivan, Anjali Nath, Michelle Keyes, Qiong Yang, Martin G. Larson, Vasan Ramachandran, Randall T. Peterson, Thomas J. Wang, Kathleen Corey, and Robert E. Gerszten. J Clin InvestInsight 2017 May 4;2(9). PMID: 28469090.

Aptamer-based proteomic profiling reveals novel candidate biomarkers of cardiovascular disease. Debby Ngo, Sumita Sinha, Dongxiao Shen, Eric Kuhn, Michelle Keyes, Xu Shi, Mark Benson, John F. O’Sullivan, Hasmik Keshishian, Laurie Farrell, Michael A. Fifer, Ramachandran S. Vasan, Marc Sabatine, Martin G. Larson , Steven A. Carr,  Thomas J. Wang, Robert E. Gerszten. Circulation 2016; 134:270-285. PMID: 27444932.

Integrative analysis of iPS cell models of PRKAG2 cardiomyopathy identifies AMPK as a regulator of cardiomyocyte survival, contractility and fibrosis in microtissues. Travis Hinson, Anant Chopra, Calvin C. Sheng, Rajat M. Gupta, Rajarajan Kuppusamy, John F. O’Sullivan, Glenn Rowe, Joshua Gorham, Kiran Musunuru, Robert E. Gerszten, Sean M. Wu, Christopher Chen, Jonathan E. Seidman, Christine E. Seidman. Cell Reports 2016 Dec 20;17(12):3292-3304. PMID: 28009297.

Rapid and efficient generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Christoph Patsch, Ludivine Challet-Meylan, Eva Christina Thoma, Eduard Urich, Tobias Heckel, John F O’Sullivan, Stephanie J Grainger, Friedrich G Karpp, Lin Sun, Klaus Christensen, Yulei Xia, Marie Florido, Wei He, Wei Pan, Michael Prummer, Curtis Warren, Oliver Wernet, Roland Jakob-Roetne, Ulrich Certa, Ravi Jagasia, Per-Ola Freskgård, Isaac Adatto, Dorothee Kling, Paul Huang, Leonard I Zon, Elliot Chaikof, Robert E. Gerzsten, Martin Graf, Roberto Iacone and Chad A. Cowan. Nature Cell Biology 2015 Aug;17(8):994-1003. PMID: 26214132.

Increases in Myocardial Workload Induced by Rapid Atrial Pacing Trigger Alterations in Global Metabolism. Turer AT, Lewis GD, O’Sullivan JF, Elmariah S, Mega JL, Addo TA, Sabatine MS, de Lemos JA, Gerszten RE. PLoS One. 2014 Jun 16;9(6):e99058. PMID: 24932507.

β-Aminoisobutyric Acid Increases Browning of White Fat and Hepatic β-Oxidation and is Inversely Correlated with Cardiometabolic Risk Factors in Humans. Lee D. Roberts, Pontus Boström, John F. O’Sullivan, Robert T. Schinzel, Gregory D. Lewis, Youn-Kyoung Lee, Melinda J. Palma, Sondra Calhoun, Ming-Huei Chen, Vasan S. Ramachandran, Martin G. Larson, Claude Bouchard, Tuomo Rankinen, Amanda L. Souza, Clary B. Clish, Thomas J. Wang, Alexander A. Soukas, Chad A. Cowan, Bruce M. Spiegelman, Robert E. Gerszten. Cell Metabolism Volume 19, Issue 1, 96-108, 7 January 2014. PMID: 24411942.

2-aminoadipic acid is a novel biomarker of diabetes risk and modulates glucose homeostasis. Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, Ghorbani A, O’Sullivan J, Cheng S, Rhee EP, Sinha S, McCabe E, Fox CS, O’Donnell CJ, Ho JE, Florez JC, Magnusson M, Pierce KA, Souza AL, Yu Y, Carter C, Light PE, Melander O, Clish CB, Gerszten RE. J Clin Invest. 2013 Oct 1;123(10):4309-4317. PMID: 24091325.

Multi Detector Computed Tomography Accurately Defines Infarct Size, but not Microvascular Obstruction After Myocardial Infarction (MI). John F O’Sullivan, MD, PhD, Anne-Laure Leblond, PhD, John O’Dea, MD, Ivalina Hristova, BS, Sujith Kumar, DMRIT, Noel M Caplice, MD, PhD. J Am Coll Cardiol. 2013;61(2):208-210. PMID: 23177294.

Microribonucleic acids for Prevention of Plaque Rupture and Instent Restenosis: “A Finger in the Dam”. John F O’Sullivan, Kenneth Martin, Noel M Caplice. State of the Art Paper. J Am Coll Cardiol 2011 Jan 25;57(4):383-9. PMID: 21251577.

Potent Long-term Cardioprotective Effects of Single Low Dose Insulin-like Growth Factor-1 (LD-IGF-1) Treatment Post Myocardial Infarction. John F O’Sullivan, Anne-Laure Leblond, Geraldine Kelly, Arun HS Kumar, Pat Metharom, Ivalina Hristova, Niki Alizadeh-Vikali, Brian G Hynes, Rosemary O’Connor, Noel M Caplice. Circulation: Cardiovascular Interventions 2011;4:327-335. PMID: 21712526.

Potent EPC conditioned media induced anti-apoptotic, cardiotrophic and proangiogenic effects post myocardial infarction are mediated by IGF1. Brian Hynes, Arun HS Kumar, John O’Sullivan, Anne-Laure Leblond, Sharon Weiss, Jeffrey Schmeckpeper, Kenneth Martin, Noel M Caplice. Eur Heart J 2011 Dec 15. PMID: 22173909.

Thrombin Stimulates Smooth Muscle Cell Differentiation From Peripheral Blood Mononuclear Cells via Protease-Activated Receptor-1, RhoA, and Myocardin. Kenneth Martin, Sharon Weiss, Pat Metharom, Jeffrey S Schmeckpeper, Brian G Hynes, John F O’Sullivan, Noel M Caplice. Circulation Research 2009;105:214-218. PMID: 19574550.

Soft tissue neoplasm invading the heart with associated thrombus in a 74 year old man. John O’Sullivan, David Kerins, Peter McEneaney, Carl Vaughan Eur J Echocardiogr. 2007 Jul 30. PMID: 17669689.

Massive thrombus in the aortic arch: A 59-year-old lady with an unknown familial predisposition to vascular thrombosis. O’Sullivan J, Kerins D, Vaughan C. Eur J Echocardiogr. 2007 Sep 19. PMID: 17888744.