Meaningful collaborations with heart

For cardiologist and scientist Dr John O'Sullivan, his research and clinical work is made possible by meaningful and long-lasting collaborations. As the Cardiometabolic Disease Group Leader with the Heart Research Institute (HRI) and University of Sydney’s Charles Perkins Centre, and a senior lecturer from the University’s Central Clinical School and Sydney Medical School, his work in the unique space at the Charles Perkins Centre allows him to take a global approach to solving the issues that come from cardiometabolic disease.

Going global

John was trained as a cardiologist in his native Ireland, where he also completed a PhD at University College Cork. His cardiology training required him to travel widely, culminating in a postdoc at Massachusetts General Hospital, Harvard Medical School, and the Broad Institute of Harvard and MIT. He also worked with the famous Framingham Heart Study, the foremost community-based cohort in the world that discovered our risk factors for cardiovascular disease, a study upon which he has drawn for his subsequent research.

From abroad, John was attracted to Sydney by David Celermajer and other eminent cardiologists in the Sydney Local Health District, and especially by the multidisciplinary metabolic focus of the Charles Perkins Centre. So many of the research experts at CPC, including the HRI, aligned well with his focus on cardio metabolic health.  For example, Professor David James’s expertise in metabolism, and with Professor Stephen Simpson in nutrition science, have been invaluable in piecing together the primary puzzle for John: the link between metabolic disease and cardiovascular disease, particularly heart failure.

Research through collaboration

Heart failure has two major phenotypes, one where the heart cannot squeeze, and one where it cannot relax. Fittingly, many of the original discoveries about heart failure causes, in the impaired squeeze type of heart failure, were made in the Framingham Heart Study in the 1950s and 1960s and several lines of pharmacotherapy have been developed for this type of heart failure.The impaired relaxation type of heart failure has become the most common type of heart failure, but we have no therapies, despite equally bad outcomes. This type of “stiff” heart failure (also caused HFpEF) has risen in frequency in parallel with the rising incidence of metabolic disease at least in part driven by modern refined diets.  It is in this area that John has benefited from the rodent dietary work of Steve Simpson. Through a combination of high fat diets and  hypertensive stress, mice very quickly developed Stiff Heart Failure, providing an excellent model of the human scenario.

John is especially delighted that right in the CPC building, the world’s largest heart biobank allows him to investigate HFpEF, run by his lab partner Dr Sean Lal. Not only does he have access to frozen heart tissue, but thanks to a research collaboration with Professor Paul Bannon (Head of Cardiothoracic at RPA) he is able access fresh heart tissue from the left ventricle, keeping the slices alive for up to a week and examining how the tissue reacts to different agents. This is a unique collaboration between surgeon and researcher.

The ability to keep this fresh heart tissue is the result of another collaboration between John and Dr Anna Waterhouse (HRI Fellow Award recipient and Charles Perkins Centre member), made possible with the unique opportunities made possible by the Charles Perkins Centre. Anna has invented a 3-D printed device that keeps the heart tissue slices alive and allows modelling of the pumping.

Improving the heart through sleep

The HFpEF clinic John and Sean Lal have created at RPA is the first clinic of its type to be so well resourced. And here, John has sought another collaborator: Charles Perkins Centre sleep expert Professor Peter Cistulli. All clinic patients get a sleep apnea assessment. It has been found that –those patients with more severe sleep apnea symptoms also have more severe HFpEF, and studying the patients sleep health will help understand the relationship of sleep apnoea to HFpEF.

“I fulfill my mission in world-class facilities,” John said of working in the Charles Perkins Centre space. It is all possible because of the local clinical and research expertise here and in the Local Health District, including the metabolomics mass spectrometry facilities,  our clinic, availability of fresh heart tissue, and the heart bank. “My collaborators at the centre enhance my research by providing allied expertise in closely related fields.”