HEART RESEARCH INSTITUTE Annual Report 2019
30 YEARS AT THE HEART OF DISCOVERY 2019 Heart Research Institute Annual Review Contents
Dr Sabine Kossman
2 2019 Heart Research Institute Annual Review Contents
CONTENTS
Our Mission 4
HRI in 2019 5
Chairman’s Report 6
Director of Cardiovascular Research Report 7
2019 Research and Media Highlights 8
Atherosclerosis and Vascular Remodelling Group 12
Cardiometabolic Disease Group 13
Cardiovascular Medical Devices Group 14
Cardiovascular Neuroscience Group 15
Cardiovascular-protective Signalling and Drug Discovery Group 16
Clinical Research Group 17
Coronary Diseases Group 18
Haematology Research Group 19
Heart Rhythm and Stroke Prevention Group 20
Thrombosis Group 21
Vascular Complications Group 22
Vascular Immunology Group 23
Fundraising Report 24
Notable Awards 25
Board of Governors 27
3 2019 Heart Research Institute Annual Review Our Mission
Our short and OUR MISSION long-term objectives
The mission of the Heart Research Institute (HRI) is to prevent death and suffering from cardiovascular disease through an understanding of the biological processes that cause atherosclerosis and thrombosis, the major underlying causes of most heart attacks and strokes.
SHORT TERM LONG TERM The major short-term focus of our research There are four long-term objectives for is to understand the development and our research: progression of atherothrombotic conditions in 1. To investigate mechanisms contributing to which the arteries are narrowed and restricted the pathogenesis of cardiovascular disease. due to a build-up of fatty deposits. 2. To develop new ways to detect symptoms This is being achieved via scientific and clinical of cardiovascular disease before it leads to research work conducted by the scientific clinical problems. groups that make up the HRI, from basic 3. To develop new treatments that can reverse biomedical discovery work, drug discovery the development of heart disease. and development, and devices and device improvement, to clinical trials and clinical 4. To prevent individuals developing initiatives. cardiovascular disease in the future.
LOCATIONS 12 SCIENTIFIC GROUPS
• 7 Eliza Street, Newtown • Applied Materials (departed July 2019)
• Charles Perkins Centre, The University • Atherosclerosis and Vascular Remodelling of Sydney • Cardiac Imaging (departed December 2019) • Cardiometabolic Disease Chairman • Cardiovascular Medical Devices Professor Len Kritharides • Cardiovascular Neuroscience (established Director of Cardiovascular Research January 2019) Professor Shaun Jackson • Cardiovascular-protective Signalling and Drug Chief Executive Officer Discovery (joined July 2019) Dr Stephen Hollings • Clinical Research Deputy Director Research Strategy • Coronary Diseases Professor Ben Freedman OAM • Haematology Research Acting Scientific Director Emeritus Professor Carolyn Geczy • Heart Rhythm and Stroke Prevention • Thrombosis Clinical Director Professor David Celermajer AO • Vascular Complications Associate Directors of Research • Vascular Immunology Management and Education Dr Mary Kavurma (Eliza St) Assoc Professor Simone Schoenwaelder (Charles Perkins Centre)
OUR PARTNERSHIPS • Sydney Local Health District and • Charles Perkins Centre, The University Sydney Health Partners of Sydney - Royal Prince Alfred Hospital Australian Business Number - Sydney Research 41 003 209 952
4 2019 Heart Research Institute Annual Review HRI in 2019
HRI IN 2019
PRESENTATIONS Domestic | 71 International | 101
INTERNATIONAL COLLABORATIONS 110+ collaborations across 44 countries
STUDENTS TRAINED OR MENTORED Honours students | 18 PhD students | 20 Visiting students | 6
106 190 52 Discoveries published in Citations by external world-wide Scientific projects currently peer-reviewed journals researchers to work published being undertaken by HRI researchers
TOTAL INCOME $24,614,272 2019 HRI INCOME
Grants $5,910,281 (24.00%) 2019 grant income by funding body
Universities Research Block NSW Department National Health $575,158 Grants of Health and Medical (2.30%) $824,199 $1,339,302 Research Council (3.30%) (5.40%) $1,839,666 (7.50%)
Fundraising (incl Bequests) $18,703,991 (76.00%)
National Heart Australian Other Foundation Research Council $935,077 Download a full list of HRI publications and $32,864 $364,016 (3.80%) presentations: www.hri.org.au/about/reports (0.10%) (1.50%)
5 2019 Heart Research Institute Annual Review Chairman’s Report 2019
CHAIRMAN’S Professor REPORT 2019 Len Kritharides
As I write this report we are in the midst of the There has been significant expansion of HRI We were very pleased to have former Minister COVID-19 pandemic. Hundreds of thousands scientific agenda in 2019. There were two Bruce Baird AM join our Board in 2019, and of people have been infected around the world new units: Dr Melissa Farnham established have benefited greatly from his insight and by a previously unheard-of virus, and thousands the Cardiovascular Neuroscience Unit and engagement. Our management team led by have died. After an Australian summer Dr Xuyu Liu established the Cardiovascular- CEO Dr Stephen Hollings has worked very characterised by drought, bushfires and floods, protective Signalling and Drug Discovery Unit hard to continuously improve every aspect of many of our comforting routines have been at HRI. Clinical trials are emerging as major HRI’s processes, including financial reporting, discarded as we face a world full of uncertainty. opportunities for HRI with National Health and information systems, human resources and scientific reporting. Photos from 1918–1919 showing young men Medical Research Council (NHMRC) funding of Associate Professor Sanjay Patel’s clinical trial and women dressed in their finery for a night Proximity to the Royal Prince Alfred Hospital of colchicine in collaboration with Professor on the town while wearing facial masks to (RPAH) and the world-class clinical care it Tony Keech of the NHMRC Clinical Trials Unit, ward off influenza, seemingly implausible just provides has always been a priority for HRI. and a major international initiative into Phase months ago, resonate with all of us today. We were therefore pleased to be able to 2 trials for stroke treatment using a novel Despite the enormous progress we have made recommit to a further five years of occupation blood thinner developed by Professor Shaun in all aspects of medicine in the last 100 years, of the Charles Perkins Centre on The Jackson’s lab. The commercialisation pipeline University of Sydney Camperdown campus. our continuing vulnerability to disease is a at HRI has been strengthened significantly by The opportunities to further expand the constant. It is only rigorous scientific insight a dedicated Board subcommittee led by Mrs footprint of HRI on site with RPAH are being that provides us with the light at the end of the Sandra Boswell, and we have seen a rapidly actively pursued through our partnership tunnel during such bleak times. We fall back on expanding portfolio of commercially exciting with the SLHD, the Centenary Institute, the medical science, its judicious application by our therapeutic and diagnostic agents emerge. Woolcock Institute and The University of political leaders, and community resilience at Our core business of producing leading Sydney to fund a state-of-the art research times of health crisis. biomedical research has been flourishing. facility linked to the planned redevelopment So, what does COVID-19 have to do with the Numerous groups received Category 1 funding of RPAH. work of the Heart Research Institute (HRI)? from the NHMRC, Australian Research There is much to be proud of, and much more Cardiovascular disease is a world-wide scourge Council (ARC) and Heart Foundation this year, to do if we are to provide the clarity of vision that kills far more people annually than we including personal NHMRC Investigator Grant needed to combat cardiovascular disease. have tallied thus far with COVID-19, has done funding for Professor Jackson and a University We are indebted to our resolute supporters so in the Western world for more than 50 years, of Sydney Robinson Fellowship for Dr Anna and donors who have entrusted us to take and in the developing world has outstripped Waterhouse. Our researchers also received this journey. infectious disease as a cause of death. some noteworthy awards (see page 25). Cardiovascular disease is common, deadly and Our Board members have contributed disabling, yet heart disease and its antecedents generously of their time and expertise, keeping Professor Len Kritharides are strangely unrecognised by our community. the organisation’s governance strong, ensuring MBBS, PhD, FRACP, FCSANZ, FAHA, FESC, FACC The research scientists of the HRI generate we are accountable to our donors and Chairman medical science that challenges nihilism and funding body partners, and facilitating strong complacency in heart disease and stroke. partnerships with the Sydney Local Health This is why the work of HRI is so important. District (SLHD) and The University of Sydney.
6 2019 Heart Research Institute Annual Review Director of Cardiovascular Research Report
DIRECTOR OF Professor CARDIOVASCULAR Shaun Jackson RESEARCH REPORT
It is my pleasure to provide you with an update on the scientific activities at HRI and to share with you the new opportunities and challenges we face in the coming years. As highlighted by our Chairman, Professor Len Kritharides, recent events with the coronavirus pandemic (COVID-19) have profoundly affected us all. We are living in this most challenging of times, and the pandemic is having a huge impact on many aspects of our work, social activities and everyday family life.
While COVID-19 has been devastating to many communities around the world, we have been relatively fortunate so far here in Australia, having avoided the huge novel anti-inflammatory and antithrombotic new funding mechanisms to support number of infections that was feared back in agents to reduce organ injury in COVID-19 our critical research and will update our March, which had the potential to devastate patients. We also have active research supporters on our research developments our communities and healthcare system. programs in diabetes, hypertension (high blood over the coming months. pressure) and the metabolic disturbances Clearly, we all need to remain vigilant and As many of you know, I am incredibly proud associated with these disorders. These continue to support each other during this of our hard-working staff and students at HRI. research programs have been boosted by difficult time. I am supported by an outstanding executive many new recruits to the Institute and our team, including Dr Stephen Hollings (Chief Our work at HRI has never been more close working relationships with scientists at Executive Officer), Professor Ben Freedman important, as many of the people most the Charles Perkins Centre and our clinical (Deputy Director Research Strategy), vulnerable to the severe complications of colleagues at the Royal Prince Alfred Hospital. Emeritus Professor Carolyn Geczy (acting COVID-19 infections have cardiovascular We are therefore well placed to make Scientific Director), Richard Wylie (Director disease. It is not just the elderly with chronic important contributions to the understanding of Fundraising and Brand), Elissa Dwyer cardiovascular or respiratory disease that and treatment of COVID-19 patients. (Director of Human Resources) and Vania are most at risk of severe illness, but also While we have had a very successful year in Dauner (Executive Assistant). I have also individuals with high blood pressure, obesity securing numerous prestigious grants and enjoyed wonderful support from our Chair, and diabetes. These are the people who are fellowships for our research, the ability of Professor Len Kritharides, and our Board more likely to be admitted to hospital and HRI to conduct its groundbreaking research of Governors who have put in an enormous require intensive medical care, often ending has always been critically dependent on the amount of effort to support our efforts. up with respiratory failure that requires generous support from our regular donors, I am truly grateful for all their hard work. ventilation. These latter patients have a many of whom have supported HRI for poor prognosis with a high death rate. Even Finally, and most importantly, I’d like to years. For that, we are immensely grateful. if these patients survive, the concern is that thank HRI’s wonderful donors, past and However, with the COVID-19 pandemic, we they have immense organ damage from the present, who have provided us with precious find ourselves in a precarious position as we widespread inflammation and clotting that financial support, even during these difficult have had to stop all fundraising activities, has occurred, starving their tissues of vital financial times. Your generosity is enormously which has put enormous strain on our institute oxygen and nutrients. Whether these appreciated by us all. Thank you. and scientists. We of course are not alone people will fully recover is not yet clear. in this regard, and we are very appreciative Inflammation and blood clotting of the support that we and other medical Professor Shaun Jackson (thrombosis) are two major areas of research institutes have received from the MBBS (Hons), BMedSci (Hons), PhD research strength within HRI, and we are Federal Government during this difficult time. Director of Cardiovascular Research actively exploring the potential utility of Nonetheless, we are endeavouring to find
7 2019 Heart Research Institute Annual Review 2019 Research & Media Highlights
RESEARCH & MEDIA 2019 HIGHLIGHTS
DISCOVERIES IN NEUROSCIENCE HAEMATOLOGY GROUP PROGRESS The Cardiovascular Neuroscience Group In 2019, the Haematology Group showed continued research into the cardiovascular the important role of neutrophil extracellular consequences of sleep apnoea, discovering traps in a high-risk, prothrombotic condition, important mechanisms into how the brain named heparin induced thrombocytopenia detects, processes and responds to repeated (Nat Comm 2019). This finding was made episodes of hypoxia. This work resulted in one in collaboration with Professor Ben Chong, publication in Frontiers in Neuroscience as UNSW. Also in 2019, one PhD, one Honours well as two first class Honours theses. The and three undergraduate students joined the Group’s work has won a number of awards Group. The Group was actively involved in at local conferences and has formed the basis the organisation of the 2019 International TECHNOLOGICAL ADVANCES for expanding their research direction into the Society of Thrombosis Haemostasis Meeting The Cardiovascular-protective Signalling area of glucose regulation. The Group has in Melbourne (theme leader for Coagulation and Drug Discovery Group has discovered also discovered that ketones protect against Anticoagulation Basic Research). two naturally occurring compounds – hypoglycemia-induced seizures. linoleic acid and sulforaphane, found in nuts and broccoli – exhibiting potent antithrombotic effects, which strongly associate with the cardiovascular- protective mechanism of healthy diets. In their upcoming ACS Central Science publication, they took an interdisciplinary approach through combining chemical and proteomic technologies to optimise the therapeutic features of linoleic acid, which enables it to target the key disease regulators Akt2 and Akt3 in thrombosis and breast cancers. As a result, their linoleic acid analogues engendered more potent, durable therapeutic impacts with mitigated side effects compared to other Akt drugs in clinical trials. The Group has been invited to international conferences to showcase how modern chemical proteomic technologies would accelerate drug development in the field of cardiovascular disease. The technologies developed in this research project have also become the critical supports of future investigation into the area of antithrombotic drug discovery.
Dr Rahul Kurup 8 2019 Heart Research Institute Annual Review 2019 Research & Media Highlights
HRI ON CHANNEL TEN Distinguished Professor Annemarie Hennessy AM appeared on the Morning Show, Channel Ten, with Sarah Leonardi- McGrath, a preeclampsia survivor.
19 INTERNATIONAL COLLABORATIONS The Heart Rhythm and Stroke Prevention Group collaborated with 19 international screening studies to share patient level data and combine this data in a meta-analysis to assess the impact of screening methodologies for atrial fibrillation (AF) (PLoS Med 2019). The Group also completed their rural general practice screening study into AF, with the results receiving international interest. The qualitative results were published in BMC HRI CALLS ON AUSSIES TO “Heart disease is a leading killer of Australian Family Practice and were also accepted for SUPPORT MUMS-TO-BE women. Due to the heightened risks during presentation in the digital health prize session Appeared on Channel 7 News, 30 May 2019 pregnancy, it is especially important for at the European Heart Rhythm Association Launching in-line with World Preeclampsia women to take simple actions – from planning (EHRA) conference in March 2020. The Day (22 May), HRI’s Distinguished Professor gentle exercise, to reviewing nutritional intake completion of this study has led to further Annemarie Hennessy AM spearheaded – for a healthier outlook post-partum and into funding to look at the feasibility of self- #StandByHerHRI, an educational movement later life,” says Professor Hennessy. screening for AF within general practice. from HRI targeting the support network “We know that mum is super focused on around expectant and new mothers. baby’s development during pregnancy, “We know that mum Preeclampsia and gestational diabetes so the #StandByHerHRI campaign aims to is super focused on developed during pregnancy can significantly empower the mother and those around her increase a woman’s risk of heart disease to support her in protecting her own health as baby’s development later in life, but these can be manageable well as baby’s, and ensure that simple steps during pregnancy, so the complications if monitored. are taken to help her to keep it monitored, thereby lowering her risk of cardiovascular #StandByHerHRI campaign Each year 30,000 women in Australia will complications,” added Professor Hennessy. aims to empower the develop high blood pressure during pregnancy, with 10,000 of these leading to preeclampsia. mother and those around Further still, between 12–14% of pregnant Full media report and video: women will develop gestational diabetes. her to support her in https://bit.ly/2OX1xqM protecting her own health as well as baby’s.”
9 2019 Heart Research Institute Annual Review 2019 Research & Media Highlights
“This drug basically works on a different part of the clot. We believe if we can combine it with existing therapies it might actually break up the clot better”
STROKE MEDICATION BREAKTHROUGH ADVANCES IN WOMEN’S HEALTH NOVEL THERAPEUTIC APPROACH Appeared on Channel 9 News, The Vascular Immunology Group published The Vascular Complications Group discovered 24 September 2019 research in major clinical women’s health that monocytes are a main source of TRAIL A new medication developed by HRI’s journals, such as PLOS1, Placenta, in the circulation of healthy people that is Thrombosis Group has been confirmed to be Hypertension, and the Journal of Human compromised in coronary artery disease safe in preclinical laboratory studies and has Hypertension as well as Pregnancy (CAD), such that monocyte TRAIL expression the potential to help thousands of ischaemic Hypertension. The Group also attracted their was reduced, concomitant with reduced stroke sufferers every year. first international higher degree students: plasma levels in patients. Importantly, the Dian Angraini from Indonesia and Memory Group identified a new population of TRAIL- Associate Professor Simone Schoenwaelder Ngwira from Malawi, both enrolled at Western expressing monocyte/macrophages that and PhD student Jessica Maclean discussed Sydney University (WSU). They are looking protected against atherosclerosis. Because the impact this new medication will have on at new biomarkers for preeclampsia in monocytes differentiate into macrophages patients and health care professionals around collaboration with the proteomic division and play an important role in the development the world, on Channel 9 News. of WSU, and with the Department of of atherosclerosis, they examined the effect “This drug basically works on a different part Obstetrics at the University of Malawi. of TRAIL deletion from macrophages. They of the clot. We believe if we can combine it found that macrophages lacking TRAIL with existing therapies it might actually break were more inflammatory, ‘foamier’ because up the clot better,” says Associate Professor BABYTALK: PREECLAMPSIA AND they had an impaired ability to remove Simone Schoenwaelder. YOUR HEART HEALTH cholesterol, and dysfunctional in their ability Appeared as a podcast on ABC Radio, Presently only one drug is available for to clear dead cells, which increases toxicity, 25 May 2019 stroke survivors — tPA (also referred to promoting unstable plaque. Normalising Distinguished Professor Annemarie Hennessy as thrombolysis). Only 10% of patients TRAIL levels in these cells could represent AM was invited on the Babytalk show on can use it due to side effects. a novel therapeutic approach in the treatment ABC Radio to describe her research in the of CAD. This work was in collaboration with Full media report and video: Vascular Immunology Group and the effects the Coronary Diseases Group (HRI), Anzac https://bit.ly/37DBAU0 of preeclampsia on long-term health. Research Institute, The Baker Institute, Women who experience preeclampsia are The WEHI and Cambridge University, and NHMRC GRANT AWARDED two to four times more likely to develop high was published in iScience. Associate Professor Sanjay Patel of the blood pressure in later life and twice as likely Coronary Diseases Group and colleagues to suffer a stroke or heart attack. Two out of were awarded a grant from the National three women who experience preeclampsia Health and Medical Research Council will die from cardiovascular disease. (NHMRC) to conduct the COLCARDIO-ACS Professor Hennessy believes that the stress randomised control trial, which will investigate of preeclampsia or gestational diabetes on the role of colchicine in reducing recurrent a woman’s body during pregnancy could be cardiovascular events in patients who have causing long-term cardiovascular damage. had a heart attack and have evidence of persistent inflammation. Listen here: https://ab.co/2vHj0wA
10 2019 Heart Research Institute Annual Review 2019 Research & Media Highlights
EVADING DRUG SIDE EFFECTS The Vascular Complications Group published a paper in FASEB Journal. They discovered that M3, a product secreted by the murine γ-herpesvirus during infection (similar to Epstein Bar virus in humans) and a broad spectrum inhibitor of chemokines, could inhibit inflammatory-driven (pathological) angiogenesis, but preserve hypoxia-driven (physiological) angiogenesis in two models of angiogenesis in CVD. Specifically, the Group showed that M3 attenuated cuff- induced inflammation via its ability to inhibit chemokine actions but had no effect on ischaemia-induced angiogenesis. Moreover, M3 blocked chemokine-mediated vascular FACE REVEALS DARK SECRETS BLOOD CLOTTING BREAKTHROUGH smooth muscle cell activation, proliferation OF THE HEART The Thrombosis Group is developing and migration. These findings are significant Appeared on Channel 7 News, safer anti-clotting agents derived from since current angiogenic therapies target both 28 November 2019 “Mother Nature” (PNAS 2019). The abnormal and physiological angiogenesis, HRI’s Professor Ben Freedman has powerful enzyme thrombin is by far identifying new therapeutic targets that can contributed to a world-first study that the most robust activator of platelets specifically inhibit angiogenesis because of successfully trialled an innovative tool to and blood clotting (coagulation) in both inflammation, without altering physiological pick up heart abnormalities in several people physiological haemostasis and pathological angiogenesis, is essential to evade the severe at once by studying their facial features. thrombotic response. Therapeutic inhibition side effects of these drugs. of thrombin has been shown to be an The work, published in the prestigious effective antithrombotic agent, however, journal JAMA Cardiology, could be rolled SNORING AND HEART DISEASE all current inhibitors of this enzyme lead to out in GP waiting rooms to screen for the LINK EXPLAINED severe bleeding complications. In studies common heart condition atrial fibrillation, Reported by Medical Xpress, performed in collaboration with Professor which triggers catastrophic strokes. 25 September 2019 Richard Payne at The University of Sydney’s HRI’s Cardiovascular Neuroscience Group “Sadly, many people experience this type of School of Chemistry, and joint funded by the have discovered a brain chemical that could severe, life-changing stroke, and they don’t NHMRC, the Group has characterised novel be responsible for triggering heart disease and know they are even at risk of it until it’s too anticlotting agents that have been based high blood pressure in people with the snoring late,” says Professor Freedman. around naturally occurring proteins found in condition obstructive sleep apnoea (OSA). “Our technology can quickly scan the face the saliva of mosquitos. Their studies have and pick up tell-tale signs of this heart demonstrated that these bug-derived proteins “We found that by blocking a particular PACAP problem, and pass the discovery onto the are able to dissolve blood clots in a disease receptor we could completely abolish the doctor, all without disturbing the patient in model of thrombosis with fewer bleeding response in multiple experimental models,” any way.” complications. The outcomes of these studies says Dr Melissa Farnham, Unit Leader at HRI. have laid the foundation for the development “A drug that is able to block this action in Atrial fibrillation is a common irregular of safe anticoagulants for the treatment humans would spare thousands from heart- heart rhythm disorder that affects 500,000 of thromboembolic diseases such as stroke related problems.” Australians, with sufferers at five times the in the future. risk of having an AF-related stroke, which One in 10 middle-aged Australians have OSA. tend to be larger, more severe and harder People with OSA have significantly higher than to survive than other strokes. average rates of stroke, heart disease, high blood pressure, diabetes and depression. Full media report and video: https://bit.ly/2uPZD4A The study was a collaboration also involving researchers at Macquarie University, The University of Sydney, University of Melbourne “Our technology can quickly scan the face and pick up tell- and University of Calgary, Canada. tale signs of this heart problem, and pass the discovery onto Full article: https://medicalxpress.com/ the doctor, all without disturbing the patient in any way.” news/2019-09-heart-disease-link.html
11 2019 Heart Research Institute Annual Review Atherosclerosis and Vascular Remodelling Group
ATHEROSCLEROSIS AND VASCULAR REMODELLING GROUP
DR ASHISH MISRA Group Leader PhD, MTech, BSc
OUR MISSION OUR IMPACT Factors and regulators of smooth muscle Our mission is to identify and gain insights Cardiovascular disease is the main cause of cells and macrophages in progression from the genetic and molecular pathways death globally, accounting for approximately of atherosclerosis involved in cardiovascular disorders, one third of all deaths. Currently available Atherosclerosis is a leading cause of death and exploit these pathways to provide cardiovascular therapies are not universally worldwide. Atherosclerotic plaque or better therapeutic options to eradicate effective and do not reverse the vascular atheroma consist of smooth muscle cells cardiovascular disease. disease completely. Vascular diseases (SMCs) and macrophages in the malefactor therefore place a heavy burden on the Our main objective is to broaden lesion and are comprised of a lipid-laden core healthcare system. Our work to identify understanding of the cellular and molecular covered by a fibrous cap. Plaque rapture leads the factors and signalling mechanisms mechanisms involved in blood vessel wall to thrombosis with dire consequences, such involved in cardiovascular disorders has the patterning and define the role of these as myocardial infarction and stroke. SMCs and potential to provide better options to treat pathways in vascular abnormalities and macrophages are key players in atherogenesis. and eradicate cardiovascular disease, thus complications, and then link these insights Although extensive research has been done in decreasing its burden on society at large. to translational research to improve the past on atherosclerosis, exactly how cells the prevention and treatment of human from normal blood vessel walls contribute to cardiovascular disease. atherosclerotic plaques is still far from clear. RESEARCH PROJECTS Our studies aim to discover the origin of the To this end, we employ a unique blending of The role of Notch signalling cells that make normal blood vessels and how mouse models and cultured cells, as well as in cardiovascular disease and these cells contribute to atherogenesis. human samples, with the aim of unveiling the related pathologies pathogenesis of cardiovascular diseases. Notch has been comprehensively studied as Recently, our studies established that very a conciliator of cell-to-cell communication few SMCs have the potential to migrate and Our ultimate goal is to prevent and reverse that mediates cell fate decisions of proliferate from the blood vessels and produce vascular disease to prevent heart attack progenitors. While Notch signalling has most of the SMCs in atherosclerotic plaques. and stroke. been extensively studied in cell fate The focus of our current studies is to identify determination at distinct development new signalling molecules, factors and/or stages of mammalian cells as well as pharmacological inhibitors that can modulate cancer stem cell progenitor maintenance SMC phenotypic switching and macrophage and renewal, the functional role of Notch infiltration into the plaque to change the signalling in vascular wall patterning plaque composition and thereby promote and cardiovascular disease is not well plaque stability. understood. By using advanced microscopic techniques, fate mapping approaches and single cell clonal analysis, we aim to study Find out more: www.hri.org.au/our-research/ the role of Notch signalling in blood vessel atherosclerosis-and-vascular-remodelling wall patterning and maintenance of smooth muscle cell progenitors in developing walls as well as disease of the vasculatures. Thus, we believe that the investigation of Notch signalling in vascular biology promises Cross-section of elastin knockout mouse aorta. Photo credit: Atherosclerosis and to be a very fruitful way forward to designing Vascular Remodelling Group new therapeutics.
12 2019 Heart Research Institute Annual Review Cardiometabolic Disease Group
ASSOCIATE PROFESSOR CARDIOMETABOLIC JOHN O’SULLIVAN Group Leader DISEASE GROUP MD, PhD, MSc, Cert Biostatistics (Harvard), FRACP, FAHA, FRCPI
OUR MISSION RESEARCH PROJECTS Our mission is to improve the detection Leveraging cardiac substrates to improve and treatment of cardiovascular disease cardiac energetics and outcomes in through the development of diagnostic diabetic cardiomyopathy and HFpEF markers, predictors and novel therapies The “stiff” type of heart failure, where the for cardiometabolic disorders. heart cannot relax properly, has become We aim to discover new mechanisms in the most common type of heart failure. cardiometabolic disease that we can target The 5-year mortality for both types of heart with novel therapeutic agents. We also aim failure is 75%, and the median survival for to detect early markers of disease to guide both is 2.1 years. vitamins, citric acid cycle metabolites, and timely intervention. Our research revolves While a range of therapies has been developed a potent effect on tryptophan metabolism around two major themes: for the better-understood impaired-squeeze that confers anti-inflammatory effects. i) uncovering the mechanism and identifying type of heart failure, shockingly there are no We are investigating further a tryptophan novel therapeutic targets in Heart Failure therapies for the stiff, impaired-relaxation type derivative that is produced exclusively preserved Ejection Fraction (HFpEF); and of heart failure, which is called Heart Failure in the gut and seems to have important preserved Ejection Fraction (HFpEF). ii) diet-microbiome-metabolism interactions roles in inflammatory-driven diseases like in cardiovascular disease. We have recently identified key pathogenic atherosclerosis and insulin resistance. changes in human and model system HFpEF left ventricular myocardium and have also identified therapeutic strategies based on OUR IMPACT “ W e aim to detect early Cardiometabolic diseases, which lead to each of these discoveries. heart attacks and stroke, have exploded We perform investigation of human heart markers of disease to guide in prevalence due to the 600% increase tissue in conjunction with Dr Sean Lal from timely intervention.” in overweight and obesity rates over the Sydney Heart Bank (over 17,000 samples, last 40 years. Our work to enable earlier one of the largest in the world). We run a detection of cardiometabolic disorders, and dedicated HFpEF clinic in our hospital, in which Novel therapeutic strategies thus enable earlier intervention, could have we use cardiac MRI to carefully characterise in type 2 diabetes a transformative impact on the health of key features of HFpEF including extracellular Working in partnership with the Garvan the hundreds of millions of people around volume, microvascular disease and fibrosis. Institute, we apply our omic technology Australia and the world who are at risk of We have extensive tools to probe mechanism to deeply-phenotyped cohorts of patients diabetes and cardiovascular disease. including, in conjunction with HRI’s Dr Xuyu with liver and muscle insulin resistance to In our first theme, we have developed Liu, chemo PROTAC technology to enhance guide targeted type 2 diabetic therapy. We comprehensive resources with which to make drug docking and cardiospecificity. We also have identified signatures of hepatic insulin novel insights: our own diabetic cardiomyopathy perform primary cardiomyocyte culture and resistance and of skeletal muscle insulin clinic; cardiac MRI; metabolomics and have iPSC-cardiomyocyte models to further resistance, which we will use to guide genomics platforms; in vivo murine models; model disease. therapy using medications that target either of these organs. We are now testing an ex vivo perfusion Langendorff model; iPSC- Dietary-microbiome-metabolic interactions whether our signatures of liver insulin cardiomyocytes, including several lines carrying in cardiovascular disease loss-or gain-of-function variants in metabolic resistance predict response to treatment We are studying the interaction of dietary pathways relevant for cardiovascular disease; with metformin, the first agent in the macronutrients with the microbiome, gut and and stable-isotope flux analysis. type 2 diabetes treatment algorithm that plasma metabolome on cardiac phenotypic targets the liver. In our second theme, we use matched diets, expression. Recently, we discovered a microbiome analysis, faecal and plasma profound effect of high dietary fibre (resistant metabolomics, and careful cardiovascular starch) diets on microbial profile and the Find out more: www.hri.org.au/our-research/ phenotyping, and have already identified plasma redox system, energetics, gut-derived cardiometabolic-disease several novel pathways.
13 2019 Heart Research Institute Annual Review Cardiovascular Medical Devices Group
Cardiovascular Medical Devices team. L-R: Jun Ki Hong, Alexander Ruhoff, Anna Waterhouse, Jasneil Singh, Sally Gao
CARDIOVASCULAR DR ANNA WATERHOUSE Group Leader MEDICAL DEVICES GROUP PhD, BSc (Hons I)
OUR MISSION always penetrate the biofilm and the overuse Our mission is to understand the interaction of of antibiotics is leading to antibiotic-resistant medical devices with patients’ blood, proteins pathogens. Increased understanding of and cells, with a view to develop more biointerface interactions and methodology sophisticated and compatible materials for to assess materials could lead to the medical devices. development of new, more compatible materials and devices to reduce the use of We focus on how medical devices – such as drugs, improve diagnostics for early disease artificial hearts, stents and bypass machines detection and reduce risks for patients. – interact with the body. The team applies cutting-edge bioengineering tools to develop new techniques to assess and understand RESEARCH PROJECTS Device failure mechanisms and how different the interplay of events at the biointerface and Biointerfaces disease states contribute to them can be manipulate this interplay to improve medical Understanding the interactions of medical investigated with the aim of developing new device function as well as create novel devices with patients’ blood, proteins and treatments or preventative therapies. devices, diagnostics and drug and non-drug- cells will allow the development of more based avenues for therapies. Bioengineering smart materials sophisticated and compatible materials Medical device thrombosis and biofouling Our goal is to develop materials that reduce for medical devices for the diagnosis and leading to sepsis cause significant morbidity foreign reactions in the body, and to reduce treatment of cardiovascular disease. and mortality worldwide. Furthermore, the incidence of blood clot formation and To achieve these goals, we utilise cutting- there is an urgent need to reduce the biofouling. edge bioengineering tools to develop new complications that arise from drugs methodologies to assess and understand the designed to combat these issues, such as interplay of events at the biointerface. This anticoagulants that cause bleeding and the OUR IMPACT includes immobilising proteins or creating overuse of antibiotics that result in antibiotic Despite the widespread use of medical devices anti-adhesive coatings and investigating the resistant pathogens. Using bioengineering in cardiovascular medicine – including artificial biological response at the interface of the strategies, increasingly sophisticated hearts, vascular stents, vascular grafts, materials using advanced microscopy and materials can be constructed. By combining heart valves, pacemakers, catheters and surface analysis tools. physical, chemical and biological surface cardiopulmonary bypass circuits – many side Biomimetic model systems modification methods, medical devices can effects, such as blood clots (thrombosis) and Advances in material fabrication techniques be manipulated to interact with, repel or microbe adhesion (biofouling), are promoted and 3D printing in micro and nanotechnology adhere proteins or cells to improve medical by the materials used to make these devices. have revolutionised bioengineering, allowing device function, create novel diagnostics and Thrombosis of medical devices is currently high precision manipulation of materials for medical devices, and both drug and non- managed with medication that can cause modelling medical systems and devices in the drug-based avenues for therapies. additional complications, such as bleeding lab. Using these strategies, biomimetic in vitro from antiplatelet or anticoagulant drugs. model systems can be generated to recreate Additionally, biofouling is treated with physiological conditions to evaluate medical Find out more: www.hri.org.au/our-research/ antibiotics; however, antibiotics cannot device materials, geometries and drugs. cardiovascular-medical-devices
14 2019 Heart Research Institute Annual Review Cardiovascular Neuroscience Group
CARDIOVASCULAR NEUROSCIENCE GROUP
DR MELISSA FARNHAM Group Leader PhD, BSc (Hons I)
OUR MISSION Results have the potential to dramatically that is likely to cause most of the subsequent Our focus is on how the brain controls expand our knowledge into the effects of pathological metabolic changes, is mediated breathing and blood pressure. We are intermittent stimulation and the capacity for by intermittent release of small amounts of interested in what goes wrong in the brain plasticity to occur in primitive, life-sustaining PACAP that act on PAC1 receptors located to result in the development of cardiovascular areas of the brain. PACAP receptors could be a on sympathetic neurons in the spinal cord. disease. We study peptides and their receptors useful therapeutic target, opening the exciting Low carbohydrate (ketogenic) diet in type 1 in cardiovascular, autonomic, centres of prospect of pharmacotherapy to mitigate the diabetes: do ketones protect the brain from the brain. Our current research aims to cardio-metabolic complications of OSA. adverse effects of hypoglycaemia? understand the central mechanisms driving Type 1 diabetes accounts for 10–15% of the sympathetically mediated increases Australian diabetic patients. Type 1 diabetic in blood glucose and blood pressure in “ W e are interested in what patients are prone to repeatedly experiencing models of sleep apnoea. By understanding low blood sugar levels (hypoglycaemia), which the mechanisms driving the cardiovascular goes wrong in the brain to results in a condition called hypoglycaemia consequences of sleep apnoea, we aim to result in the development unawareness. This condition, termed identify new therapeutic targets to treat of cardiovascular disease.” ‘hypoglycaemia-associated autonomic sufferers and reduce disease burden. failure’ (HAAF), is life-threatening for type 1 diabetic patients.
OUR IMPACT RESEARCH PROJECTS Glucose is the major energy source for Cardiovascular disease (CVD) remains The autonomic consequences of sleep the brain under normal physiological the leading cause of death in Australia and apnoea: a critical role for PACAP conditions. However, during extended fasting, worldwide. It is often present with other OSA is characterised by repetitive pharyngeal following exercise, or while on a high fat/low confounding conditions such as obesity or collapse during sleep, with resultant oxygen carbohydrate (ketogenic) diet, an alternative obstructive sleep apnoea (OSA), both of desaturation (intermittent hypoxia) and source of energy becomes available – ketone which are independent risk factors for CVD. sleep fragmentation. Metabolic effects of bodies. Although ketones are effective in the The global burden of OSA is recently intermittent hypoxia occur rapidly. These early preservation of brain cognitive functions under estimated as approximately 1 billion people changes could initiate triggers that promote hypoglycaemic conditions in type 1 diabetic and is comorbid in 30–80% of cardiovascular insulin resistance and development of type 2 patients, the effects of ketones on brain (particularly hypertension) conditions and diabetes in human OSA conditions. reflex response to recurrent hypoglycaemia and the development of HAAF in this patient in approximately 70% of diabetics. The Importantly, PACAP (an excitatory population are unknown. associated Australian healthcare and neuropeptide) and its receptors are present in economic costs due to comorbid disease areas of the rodent brain activated by hypoxia; The aim of this project is to investigate and lost productivity are over $5 billion per these areas control both blood pressure and the low carbohydrate ketogenic diet as year and are largely attributed to undiagnosed blood glucose. In humans, genetic variations a potential strategy in preventing the OSA. In conditions such as OSA, excess in PACAP or its receptors (PAC1 and VPAC) detrimental consequences of insulin-induced sympathetic activity may trigger development are linked to sleep and metabolic disorders. hypoglycaemia and the development of of cardiometabolic diseases, but research Our focus is on how intermittent stimulation hypoglycaemia-associated autonomic failure and concrete evidence is lacking. of brain circuits regulate blood glucose and (HAAF) in type 1 diabetes. We aim to significantly advance this research blood pressure. area. Our unique models and techniques are We recently showed that PACAP is necessary Find out more: www.hri.org.au/our-research/ designed to uncover a previously unexplored in the brainstem for the sympathetic cardiovascular-neuroscience mechanism that suggests OSA induces response to acute intermittent hypoxia. autonomic plasticity, driven by PACAP, which Our exciting new data indicates that the is important in the pathogenesis of CVD. characteristic sympathoexcitation of OSA,
15 2019 Heart Research Institute Annual Review Cardiovascular-protective Signalling and Drug Discovery Group
CARDIOVASCULAR-PROTECTIVE SIGNALLING AND DRUG DISCOVERY GROUP
DR XUYU LIU target spectra of sulforaphane and alliin Group Leader using Activity-Based Protein Profiling PhD, MSc, BSc (ABPP) technology, and characterise the antithrombotic effects of natural supplements in thrombosis mouse models. This research is partially conducted in collaboration with the Payne research group (School of Chemistry, The University of Sydney).
Chemical synthesis and phenotypic OUR MISSION OUR IMPACT validation of precision proteolysis Our mission is to better understand the Thrombotic complication is the leading targeted chimeras (PROTACs) for therapeutic mechanisms of cardiovascular- cause of mortality and accounts for one cardiovascular disease protective natural supplements in platelets in four deaths worldwide. Despite intense The Akt kinases are critical regulators of cell and the heart, and use this knowledge to investigation over the past decades, the physiology, but have also been associated with develop next-generation precision medicine discovery of novel cardiovascular drugs the development of thrombosis, cancer and for the prevention and treatment of life- has remained disappointingly low. Novel other major killer diseases. This kinase family threatening thrombosis and ischaemic stroke. antithrombotic drugs entering clinical is composed of three highly homologous testing has stalled due to the large attrition isoforms (with 73% sequence similarity): Akt1, Recently, there has been considerable in investment and increasing demand in Akt2 and Akt3. Gene knockout studies have interest in the development of natural risk assessment. However, the existing shown that Akt isoforms have non-overlapping supplements for cardiovascular-protective antithrombotic drugs such as aspirin and regulatory functions in cell which contribute to therapeutics, due to their inherent safety clopidogrel are ineffective, with less than their pathological and physiological diversity in profiles and the clinical evidence for 15% of diabetic patients taking these vivo. For example, both Akt2 and Akt3 regulate ameliorating chemotherapy-induced medicines avoiding a fatal thrombotic event. platelet activation in thrombosis, whereas cardiovascular complications. However, This situation is likely to worsen in the near Akt1 knockout mice develop a severe defect in it remains a huge challenge to understand future due to the rapidly growing incidence haemostatic plug formation. This observation the cardiovascular-protective mechanisms of obesity and diabetes. together with the well-established Akt- at the molecular level, which impedes isoform signalling in the cardiovascular pharmacological optimisation of these The chemical biology research approach system underscore the urgent need of Akt- bioactive agents for therapeutic use. adopted by our group is designed to identify isoform-specific inhibitors for next-generation effective and durable antithrombotic therapy Our research aims to determine the precision medicines. inspired by natural supplements, and to protective mechanisms underlying heart- repurpose anti-cancer and anti-inflammatory Recently, the revolutionary approaches in drug healthy diets and herbs, and apply this drugs for thrombotic conditions. development termed PROTAC (PROteolysis- knowledge to design and develop safer and TArgeting Chimera) have attracted more effective cardiovascular therapeutics. considerable attention in repurposing broad- To this end, we focus on the development RESEARCH PROJECTS spectrum therapeutics to be target-selective of new proteomic platforms to enable Understanding heart-healthy diets at the degraders. Importantly, rational design of genome-wide understanding of how natural molecular level PROTAC constructs has led to isoform-specific supplements and drugs perform in the Sulforaphane and alliin are known to be the degraders to target oncogenic kinases and context of cardiovascular complications, cardioprotective “ingredients” in broccoli transcription factors otherwise intractable and on constructing a comprehensive and onion diets. They have been shown to to functional inhibition. chemical-proteomics database to reveal promote cardiomyocyte survival against This project aims to develop Akt-isoform- the therapeutic impacts on thrombosis ischaemic injury and exhibit potent anti- specific PROTACs and to investigate their at the cellular and molecular level. cancer activity by potentiating apoptosis. therapeutic potential in thrombosis. However, the protein target spectra of these We also focus on adopting new drug small molecules in cells remain unclear. discovery technologies – PROTAC and ABPP There is no unified model to explain the that have led to a tremendous achievement Find out more: www.hri.org.au/our-research/ cell-type-dependent phenotypes observed in anti-cancer drug discovery – to accelerate cardiovascular-protective-signalling-and-drug- in the treatment. Therefore, in this project, the development of precision medicine to discovery we are aiming to investigate the platelet tackle thrombosis and ischaemic stroke.
16 2019 Heart Research Institute Annual Review Clinical Research Group
CLINICAL RESEARCH GROUP
PROFESSOR DAVID CELERMAJER AO Group Leader MBBS, MSc, PhD, DSc, FAHA, FRACP, FAA
OUR MISSION RESEARCH PROJECTS and studied the pattern of blood flow and Our primary mission is to detect cardiac We have a series of projects to detect early pressure using sophisticated mathematical and vascular disease promptly in order blood vessel damage in children and young models. Papers describing this research were for treatments to be administered at an adults as well as programs to intervene published in major international journals. early, optimal stage to prevent serious late to prevent late serious complications. Young adults with congenital heart disease consequences of disease. We also study heart disease in those There are now more young adults than with congenital cardiac abnormalities Our goals are to detect and prevent children with congenital heart disease (inborn with a view to minimising complications complications from three primary types heart abnormalities), with the population and maximising quality of life. of serious heart disease: continuing to grow in number and complexity. Detecting heart attacks At the Royal Prince Alfred Hospital (RPAH), (i) Atherosclerosis – the narrowing of the In collaboration with Associate Professor we run one of the largest Adult Congenital main blood vessels in the body, and the Sanjay Patel and the Coronary Diseases Heart Disease Clinics in the country, main cause of heart attack and stroke. Group at HRI, we have discovered that the addressing medical issues such as this. Our (ii) Congenital heart disease – as an heart releases certain proteins and cell work with these young adults has focused increasing number of adults surviving remnants during a disruption of plaques on rarely studied conditions such as Ebstein’s with inborn heart problems still require (during heart attacks) and we can now anomaly of the heart, congenitally corrected extensive care and treatment. detect these in the laboratory. We also have transposition of the great arteries and (iii) Pulmonary vascular disease – the preliminary data indicating that a well-known dextrocardia (the unusual situation where the narrowing of the main blood vessels to anti-inflammatory drug, colchicine, may be heart lies on the right side of the chest rather the lungs, which can lead to overload particularly beneficial in dampening down than the left). We have also collaborated with of the right side of the heart. the inflammation associated with acute the Department of Radiology at RPAH to heart attack, with potential benefits for make important discoveries about a condition patients in this situation. Dr Gonzalo Martinez, called noncompaction of the heart, where the OUR IMPACT a cardiologist from Chile, helped perform heart is not assembled efficiently, resulting in Early detection and prevention of advanced this work, collaborating with our Group for ‘spongy’ rather than well-compacted muscle. heart disease may save hundreds of 18 months. We have discovered a new diagnostic tool to thousands of lives each year. We aim to detect detect this, using MRI of the heart, and have Early detection of pulmonary heart and blood vessel abnormalities at an also defined its prevalence in young adults vascular disease early stage before the condition becomes with congenital heart disease, as well as its Pulmonary vascular disease, or high blood irreversible. We design interventions to functional consequences. pressure in the lungs, is a very severe treat a wide range of abnormalities, with condition affecting young adult Australians a particular focus on the prevention of and (as we are increasingly finding out) older atherosclerosis in children and young adults “We aim to detect heart and Australians also. We conducted two projects who have risk factors for early heart disease, to outline novel techniques for detecting blood vessel abnormalities obesity, exposure to passive smoke in the this complication before it caused more at an early stage before the home, those who smoke themselves, or serious health problems. The first technique those with high levels of cholesterol. We condition becomes irreversible.” was based on ultrasound of the heart and also concentrate on all subject ages with examined the right ventricle, while in the pre-diabetes or diabetes, and babies who other, researchers placed a thin catheter Find out more: www.hri.org.au/our-research/ are born small at full term. in the main blood vessels to the lungs clinical-research
17 2019 Heart Research Institute Annual Review Coronary Diseases Group
ASSOCIATE PROFESSOR CORONARY DISEASES SANJAY PATEL Group Leader GROUP PhD, MBBS (Hons 1 Syd), FRACP, FCSANZ
OUR IMPACT RESEARCH PROJECTS One Australian dies from an acute Determining the effects of colchicine coronary syndrome (ACS) every 51 on smooth muscle cell plasticity in minutes. Failure to specifically target advanced atheroma persistent coronary inflammation, which This collaborative study (with the drives high rates of recurrent events, Atherosclerosis and Vascular Remodelling is likely a major factor. To address this Group at HRI) uses novel murine models problem, our program’s overarching aim of atherosclerosis to understand molecular is to: (i) elucidate new inflammatory athero-protective properties of colchicine. pathways in ACS patients and (ii) re- OUR MISSION Effects of colchicine on miRNA levels in purpose established anti-inflammatory Our mission is to reduce death and disability coronary disease patients drugs that target these pathways. We associated with heart disease by reducing We continue to collaborate with Associate have focused on colchicine, a safe, cheap atherosclerotic plaque build-up. Professor Hardiker’s groups at the NHMRC and effective anti-inflammatory agent. Clinical Trial Centre to determine effects Our research aims to develop novel Our program was the first to show that of colchicine on miRNA signatures in therapies to target atherosclerosis (arterial colchicine has striking athero-protective ACS patients. blockages) and its consequences (heart effects. Our findings are recognised attack). Our treatment mission is to develop Effects of colchicine on metabolomic internationally, with 20 papers and dedicated agents that specifically target profiles in coronary disease patients 25 presentations (at national and the inflammation that drives coronary Via collaboration with HRI’s Cardiometabolic international scientific symposia) in the plaque instability. Our work is performed Disease Group, we continue to investigate last five years. Notably, this program’s in collaboration with the Clinical Research, new mechanisms of action of colchicine in work has been cited 202 times by Vascular Complications and Atherosclerosis ACS patients. groups in 16 countries (Google Scholar), and Vascular Remodelling Groups within the demonstrating its reach. Determining the anti-atherosclerotic HRI, drawing upon their expertise in each properties of TRAIL area of research. Through collaboration with HRI’s Vascular Complications Group, we continue to study potential therapies to boost TRAIL, a novel mediator with marked anti-inflammatory and anti-atherosclerotic properties, in patients with coronary disease.
Find out more: www.hri.org.au/our-research/ coronary-diseases
18 2019 Heart Research Institute Annual Review Haematology Research Group
HAEMATOLOGY RESEARCH GROUP
DR FREDA PASSAM Group Leader MD, PhD, FRACP, FRCPA
OUR MISSION OUR IMPACT RESEARCH PROJECTS Our mission is to discover new mechanisms Current antithrombotic treatment is not Thiol isomerases as novel of clot formation that can lead to the effective or has bleeding side effects, eg, antithrombotic targets development of efficient and safer one in six patients who have had a heart We have identified a novel clotting pathway antithrombotic drugs. attack will have another attack despite that involves enzymes, named thiol optimal treatment. We aim to find answers isomerases. Inhibitors of these enzymes We have a special interest in the development to fundamental biological problems that will can be developed into drugs that treat of biochips for the detection and monitoring enable the development of new diagnostics thrombotic disease. of thrombotic tendency. We are focused on and treatments for patients with blood clots. the role of enzymes, named thiol isomerases, We are committed to discovering targets for Redox biomarkers in thrombotic disease in the development of thrombosis and their new and safe antithrombotics, such as the An imbalance of oxidants/antioxidants in our potential as novel antithrombotic targets. circulating protein von Willebrand factor. blood (redox imbalance) causes alterations An exciting new project is to define the to blood proteins that can lead to thrombosis. proteomic signature of the diabetic platelet We have found redox-modified proteins in the to identify causes for increased thrombotic blood that are associated with thrombosis. risk in patients with diabetes. In the clinical These redox biomarkers can be used to space, we are interested in the management identify patients that will benefit most from of venous thrombosis in the community and drugs that restore a healthy redox balance. high-risk thrombosis. Biochips for the assessment of Our research goals are to: (i) discover new haemostasis and thrombosis targets to prevent thrombotic complications in patients with diabetes; (ii) characterise thiol Many patients with bleeding and clotting isomerase inhibitors as new antithrombotics; disorders go undetected by routine laboratory and (iii) develop new methods to detect tests because these do not reflect the prothrombotic tendency in patients with conditions in the body’s circulation. Our group cardiovascular risk factors. uses biochips in a microfluidic system that simulates human circulation. These biochips Staining of Von Willebrand factor (green) in fixed can be used to detect a thrombotic or mouse platelets (red). Photo credit: Dr Angelina Lay, Haematology Research Group bleeding tendency in patient samples.
Find out more: www.hri.org.au/our-research/ haematology-research
19 2019 Heart Research Institute Annual Review Heart Rhythm and Stroke Prevention Group
HEART RHYTHM AND STROKE PREVENTION GROUP
PROFESSOR BEN “Our mission is to prevent FREEDMAN OAM strokes through early Group Leader detection of silent atrial PhD, MBBS, FRACP, FCSANZ, FACC, FESC, FAHA fibrillation (AF).”
OUR MISSION OUR IMPACT • Collaboration with the Poche Centre to Our mission is to prevent strokes through Our main activities are to determine how best screen for AF in Indigenous Australians early detection of silent atrial fibrillation (AF) to screen for AF at scale, and to prevent as in remote and rural NSW, NT and WA and implementing appropriate guideline-based many strokes as possible. The more people • Collaboration with researchers in Royal management. screened and treated, the more strokes we Melbourne Hospital to detect AF post- can prevent. We continue global advocacy With a clinical implementation focus we are stroke in Australia, Hong Kong and China for screening for AF through the AF-SCREEN exploring novel strategies using eHealth (SPOT-AF) International Collaboration. This is likely tools to detect unknown silent AF. AF is the to change guidelines and influence future • Collaboration with researchers at the most common abnormal heart rhythm – it is government policy and have a global impact Chinese University of Hong Kong to screen estimated that individuals over the age of 40 on stroke reduction. In fact, the Australian for AF in cardiac clinics, general practice have a one in four lifetime risk of developing Heart Foundation and Cardiac Society of and the community (over 20,000 people AF. AF is responsible for one third of all Australia and New Zealand 2018 guideline screened to date) strokes, which are largely preventable by on the management of AF had opportunistic • Collaboration with researchers in Shanghai anticoagulant medications that stop clots screening for unknown AF as its first to screen for AF in community centres from forming inside the heart. Unfortunately, recommendation, with a practice point being (AF-CATCH) (ongoing) AF is frequently silent, especially in older about use of a handheld ECG pioneered by people who are at greater risk of stroke, with • Collaboration with researchers in Hanoi our Group, quoting our Group’s work in its the first sign of AF being a severe stroke. (Vietnam) to screen in hospital to detect recommendation. AF after cardio-thoracic surgery (ongoing) Our AF screening research extends through collaborations with primary care and specialist • Collaboration with Hamburg and Gutenberg clinics in Australia, the USA, Shanghai, Hong RESEARCH PROJECTS Heart studies (Germany) on screening for AF Kong, Japan, Vietnam, Germany and the UK. • Atrial Fibrillation Screening, Management, • Collaboration with researchers in Frankfurt and guideline-Recommended Therapy (AF- Another major interest of our Group is to (Germany) about epidemiology of AF SMART) studies: in metropolitan and rural determine whether our Indigenous population (ongoing) general practice using smartphone ECG and has a higher burden of AF by screening in • Collaboration with researchers in Oklahoma a suite of eHealth tools remote and rural Australia, in collaboration (USA) to screen for AF in tribal Indian with the Poche Centre and the University of • Patient self-screening for AF in general clinics (ongoing) Auckland, NZ. practice using screening stations • Collaboration with researchers in Toyama (AF Self-SMART) (Japan) to investigate the incremental yield • Patient self-screening using a smartphone of annual screening (ongoing) ECG to identify recurrence of postoperative AF after noncardiac surgery and medical admissions: in Concord Hospital, Royal Find out more: www.hri.org.au/our-research/ Perth Hospital and Gosford Hospital heart-rhythm-stroke-prevention
20 2019 Heart Research Institute Annual Review Thrombosis Group
PROFESSOR SHAUN JACKSON THROMBOSIS GROUP Group Leader MBBS (Hons), BMedSci (Hons), PhD
OUR MISSION tissue. Despite successful recanalization of Our mission is to establish new and innovative major arteries, blood perfusion in surrounding approaches to the prevention and treatment of microvasculature supplying the tissue can heart disease and stroke, positioning Australia remain poor, a common complication known as a leader in the discovery and development as microvascular obstruction (MVO). Persistent of innovative therapies for the treatment of MVO can lead to progressive worsening of atherothrombotic diseases. heart function and infarction. Using cutting- edge techniques, we have observed previously Our research is focused on the haemostatic unappreciated in vivo changes within the and innate immune systems and their microvasculature during IR. Our findings not dysregulation in cardiovascular disease. only demonstrate an intimate spatiotemporal Our main focus is on blood cells (platelets, relationship between endothelial injury and leukocytes), blood coagulation proteases vaso-occlusion mechanisms, they also help and endothelial cells. Development of a novel preclinical explain why existing therapies remain ineffective. ischaemic stroke model While our studies are primarily aimed at defining Biomechanical sensing and blood clot Our ongoing studies have successfully new mechanisms underlying clot formation in formation: Solving a sticky clotting developed a novel mouse model of healthy individuals, and applying this knowledge problem in diabetes thrombolysis (iCAT) that for the first to better understand mechanisms leading The leading cause of death in diabetes is time allows us the ability to examine the to platelet hyperactivity (thrombosis) and cardiovascular disease, with up to 70% of efficacy of novel drugs including novel inflammation (termed thromboinflammation), deaths relating to the development of blood thrombin inhibitors to facilitate clot lysis our ultimate aim lies in the translation of our clots supplying the heart (heart attack) or (recanalization), restore perfusion in research discoveries into new therapeutic brain (ischaemic stroke). Diabetic individuals the brain, as well as determine whether approaches to treat cardiovascular diseases, are more prone to develop blood clots, and cerebral damage and cognitive impairment including heart attack, stroke, diabetes and these clots are more resistant to standard associated with stroke are reduced. We are the metabolic syndrome. anticlotting therapies. We have discovered using this model to assess the efficacy of a new biomechanical clotting mechanism currently approved and novel anticlotting OUR IMPACT severely affected by diabetes that is resistant agents to facilitate stroke treatment. Atherothrombosis is arguably Australia’s to the beneficial effects of commonly Safety and Tolerability of a novel greatest healthcare problem, affecting over used antithrombotic agents. Studies in the antiplatelet in patients with Acute 50% of the adult population. Despite intense laboratory are also examining the role chronic Ischaemic Stroke (STARS) investigation over the last 40 years into the oxidative stress plays in amplifying blood We have established a key group of discovery and development of more effective clotting in diabetes, and the mechanisms by collaborators comprised of Australian antithrombotic drugs, the impact of these which oxidative stress may modify platelet stroke clinicians and clinical trialists in therapies on mortality rates has remained receptors to enhance adhesion. the area of ischaemic stroke (Chris Levi disappointingly low. This situation is likely Developing novel approaches to the (UNSW, Newcastle), Craig Anderson, to worsen in the future due to the rapidly treatment of ischaemic stroke Candice Delcourt (RPA, The George), Bruce growing incidence of obesity, diabetes and The central goal of stroke therapy is the Campbell (RMH), Ken Butcher (POW), Tim the metabolic syndrome – diseases that prompt reperfusion of occluded blood vessels Ang (RPA)). Together we are drafting plans are typically more resistant to the benefits to minimise tissue death, with administration for a phase IIa multicentre, multinational, of “classical” antithrombotic therapy. The of “thrombolysis” (intravenous recombinant dose escalation study to evaluate the safety comprehensive research approach adopted tissue-type plasminogen activator, rtPA) – and tolerability of a novel anticlotting drug by our Group is designed to identify and the only clinically approved drug available developed in our laboratory in adults with target thrombosis risk in such diseases. to stroke patients. Despite this, the use of acute ischaemic stroke (AIS). The primary rtPA is associated with significant side effects, aim of this study is to evaluate the safety limiting its widespread use. We are working and tolerability of our novel antiplatelet as RESEARCH PROJECTS on several novel approaches to improve upon an adjunct therapy in patients with AIS, Understanding the mechanisms leading existing stroke therapies, making them safer when given in combination with current to microvascular dysfunction and poor and more effective. standard of care, and will be the basis for cerebral perfusion in stroke future phase IIb and III efficacy studies. For patients presenting with acute myocardial Developing safer anti-clotting agents infarction (AMI) or stroke, the primary goal of derived from “Mother Nature” therapy is to promptly re-open blocked arteries For further details, see Research & Media Find out more: www.hri.org.au/our-research/ (recanalization) to salvage the dying ischaemic Highlights (pages 8-11). thrombosis
21 2019 Heart Research Institute Annual Review Vascular Complications Group
VASCULAR COMPLICATIONS GROUP
DR MARY KAVURMA Group Leader PhD, BSc (Hons)
OUR MISSION The role of monocyte/macrophage endothelial cells to form microtubules, which Our mission is to understand the dependent TRAIL signals in are then stabilised by mural cells (such as pathogenesis of blood vessel disease and atherosclerosis pericytes and vascular smooth muscle cells). its complications, and using this knowledge, Atherosclerosis is an inflammatory condition Angiogenesis is critical in normal physiological identify new strategies to improve the burden and the main cause of CVD, initiated by processes and is also characteristic of many of cardiovascular disease (CVD) in people. retention of cholesterol in the vessel wall, and inflammatory diseases such as those seen in leading to the recruitment and differentiation atherosclerosis and cancer. Understanding Our research uses various models, genetic of monocytes into macrophages. TRAIL how angiogenesis is regulated under normal manipulation, and biochemical and molecular (TNF-related apoptosis-inducing ligand) and pathologic conditions is critical for biology tools to dissect how blood vessels is produced by most cells in the body. identifying new treatment options in disease. become dysregulated, with an emphasis on Intriguingly, low TRAIL levels independently changes to gene expression, vascular cell Project 1: Current anti-angiogenic therapies predict cardiovascular events and mortality, adaptation and function in both normal and not only target abnormal (pathological) and circulating TRAIL levels are reduced in abnormal settings in the blood vessel wall. angiogenesis in disease due to inflammation, patients with CVD. Importantly, our murine but they also inhibit common factors that models with TRAIL deletion have the same control angiogenesis needed for normal symptoms as CVD patients. Why TRAIL OUR IMPACT (physiological) homeostasis. Identifying levels and expression are reduced with Our research aims to understand the new therapeutic targets that can specifically atherosclerosis is presently unknown. molecular, biochemical and cellular inhibit inflammatory-driven angiogenesis, This project seeks to investigate the function mechanisms underlying blood vessel without altering physiological angiogenesis, of TRAIL, and how TRAIL’s protective diseases, focusing on atherosclerosis and its is essential to evade the severe side effects actions in atherosclerosis relate to its role complications, including peripheral vascular of these drugs. This project aims to determine in monocytes and macrophages. disease and diabetes. By providing new the effect of M3, a secreted glycoprotein, on knowledge as to how blood vessels become inflammation-induced pathological versus dysregulated in CVD and related pathologies, hypoxia-driven physiological angiogenesis our work will help uncover new strategies in vivo and in vitro using key angiogenic and therapeutics to combat disease, functional assays. ultimately improving quality of life and Project 2: Diabetics are three to four times life expectancy. more likely to develop atherosclerotic coronary and peripheral artery disease (PAD), RESEARCH PROJECTS Vascular Complications team. L-R: Dhanya conditions where narrowed arteries reduce Vascular calcification Ravindran, Dr Siân Cartland blood flow to the heart and limbs. This is a Medial vascular calcification is increasingly major risk factor for lower-limb amputation Novel mechanisms regulating recognised as a complication of aging in and increased risk of myocardial infarction. angiogenesis in disease patients with CVD such as atherosclerosis, Current interventions are insufficient in The vascular endothelium is critical for the as well as in diabetes mellitus and chronic many patients because extensive disease maintenance of cardiovascular homeostasis, kidney diseases. Importantly, medial precludes effective revascularisation. One where it maintains an antithrombotic, anti- calcification is associated with the morbidity option is to stimulate blood vessel growth in inflammatory and antiatherogenic state and mortality of these patients. For the order to restore blood flow, preserve tissue within the vessel wall. In disease, the development of new and better therapeutics, survival and maintain optimal organ function. endothelium fails in its ability to regulate comprehension of the regulation of vascular The aim of this project is to identify whether this equilibrium and results in endothelial calcification needs to be further investigated. TRAIL signals can stimulate blood vessel dysfunction. One endothelium-dependent This project seeks to investigate the development in diabetes, in the limb, and in process dysregulated in CVD is angiogenesis, contribution of TNF-ligands to vascular the heart during ischaemia. the development of new blood vessels from calcification in vascular smooth muscle cells. pre-existing vessels. This process involves the Find out more: www.hri.org.au/our-research/ proliferation, migration and differentiation of vascular-complications
22 2019 Heart Research Institute Annual Review Vascular Immunology Group
VASCULAR IMMUNOLOGY GROUP
DISTINGUISHED PROFESSOR ANNEMARIE HENNESSY AM Group Leader PhD, MBBS, FRACP
OUR MISSION OUR IMPACT RESEARCH PROJECTS Our mission is to better understand the Our research goals are to better understand The role of placenta antibodies in causes of preeclampsia (high blood pressure the causes of preeclampsia. By measuring causing blood vessel damage and in pregnancy), the condition’s impact on the functions of the placenta and predicting hypertension women during pregnancy, and the impact preeclampsia, we seek to provide new, safe A study of 351 women enrolled in a past on long-term cardiovascular health. treatment which would allow the pregnancy preeclampsia study, this work also involves We seek to develop new drug treatments to progress to full term, thus reducing the growing placentas in the laboratory and for preeclampsia. burden of premature delivery and also, long looking at the impact of specific antibodies Our research focuses on how placentas work term, the risk to women’s heart health. Our on placental growth. and the benefits of placental treatment to work is directly translatable to women in The potential for placental growth to women that we look after in clinical practice. pregnancy, resulting in an immediate impact prevent and reverse preeclampsia Professors Hennessy and Makris, and Drs through translational research efforts. Aggarwal, Chau and Shanmugalingam Placental growth factor is a recently are active physicians caring for hundreds discovered protein originating in the of women annually with preeclampsia, placenta, which is responsible for hypertension, vascular and kidney diseases. “Our research focuses on blood supply and oxygen to the placenta Our research scientists, Drs Xu (until Oct how placentas work and and baby. 2019), Liu (since Oct 2019), Pears and Welsh are experts in animal studies and in growing the benefits of placental Safer prolongation of pregnancy placentas, and thus support the projects of the treatment to women that A study of placenta growth and treatments Group. The Group is supported by the Sydney that provide for a safer prolongation of Local Health District (SLHD) and significant we look after in clinical pregnancy without premature delivery. NHMRC project grant funding administered practice.” The pharmacology of aspirin in by Western Sydney University (WSU). The preeclampsia placenta and women’s health research adds important and novel dimensions to the Aspirin as a useful drug to prevent overall research plan at HRI. Our Group has a strong international and preeclampsia is being examined in terms national reputation for the quality and effect of patient acceptability, drug dosing and its Our work is strongly driven by a women’s of our research plans. If preeclampsia could effect in preeclampsia prevention in a wide action group, The PEARLS Group, who be prevented, then one of the strongest risk population across Sydney and south provide community engagement and review western Sydney. of research plans, as well as funding to factors for women’s heart disease could also be prevented or reduced. This is an important support the Vascular Immunology Group’s Novel drug treatment for early long-term goal for women’s heart health. work. In 2019, The PEARLS Group raised over severe preeclampsia $100,000 for the Vascular Immunology Group Professor Makris is the current president of In partnership with major researchers for a PhD Scholarship and to support our early the Australia and New Zealand Preeclampsia in the USA and Sweden, the Group is career researchers to focus on improving craft group, SOMANZ (Society of Obstetric investigating the effect and safety of outcomes for women with preeclampsia Medicine of Australia and New Zealand), and new treatments targeting the placenta, and to understand its causes. The group is Professor Hennessy is the President elect for use in early severe preeclampsia. supported by a grant from the South Western of the international equivalent, the ISSHP Sydney Local Health District (SWSLHD) as the (The International Society for the Study of Women’s Health Innovation and Translation Hypertension in Pregnancy). Find out more: www.hri.org.au/our- Unit (WHITU). research/vascular-immunology
23 2019 Heart Research Institute Annual Review Fundraising Report
FUNDRAISING 2019 REPORT
Sometimes it’s only through a serious health WITH THANKS TO JJ’S WASTE crisis, or the loss of a loved one, that we stop & RECYCLING AND IN VITRO and reflect on the importance of our health TECHNOLOGIES and why it’s so vital to make the most out Since making their first donation in 2006, of every day. Cardiovascular disease, unlike 88,157 JJ’s have contributed over half a million many other conditions, can strike suddenly GENEROUS DONORS dollars towards life-saving research into and without warning. SUPPORTED HRI IN 2019 cardiovascular disease. They are one of HRI’s longest standing and most In 2019, I have been deeply moved to stand generous supporters. side by side with many HRI donors who have had loved ones taken far too soon by the In 2019, HRI was supported by 88,157 devastating consequences of cardiovascular generous donors, from Australia, New GIFTS IN WILLS RECEIVED 2019 disease. While we’ve come such a long Zealand and the United Kingdom. HRI’s These generous donors are honoured way in our understanding and treatment of local partnerships in these countries on our Hearts for Eternity memorial cardiovascular disease in the 30 years that continue to grow and enable our mission to sculpture, displayed at the entrance the Heart Research Institute has been in globally fight the world’s number one killer. of HRI’s headquarters. existence, there are still so many questions that remain to be answered. And that’s why Full list of gifts in Wills received in 2019: our donors remain so pivotal. At a time when ILLUMINATE 2019 www.hri.org.au/give/gifts-in-wills Governments are being asked to commit Our annual fundraising dinner, Illuminate, huge sums of money to support the victims celebrates and recognises some of our of bushfires, the drought and of course the most up-and-coming scientists. Sydney COVID-19 outbreak, our donors remain key Local Health District has been our longest to ensuring our research can continue to standing supporter and headline sponsor. drive forward. At Illuminate 2019, we were also honoured to receive a generous donation from the All donations (above $2) are 100% tax Posa and Batistich families in memory of deductible and larger donations might also Illuminate fundraising dinner 2019 Steven Posa, a much-loved family member qualify for ‘matched funding’ via existing who passed from a sudden heart attack. MAJOR SUPPORTERS 2019 Government schemes such as the National With these funds, we have launched the We would like to thank the following Health and Medical Research Council Steven Posa Scholarship, which will be individuals and organisations for their (NHMRC) Development Grants. This is awarded to a top emerging cardiovascular support in 2019. particularly valuable because matched medical researcher at HRI, to support them funding grows the impact of major Barry Timbrell Marcus and Linda as they complete their doctorate. donations substantially. Lagudi Eventide Homes Whether you donate as an individual or Max Hooper Gavin and Karen Bird as a family, a corporate partner, or have CHAIRMAN’S CHRISTMAS BRUNCH Medicine Today remembered HRI in your Will, you can feel The annual Chairman’s Christmas Brunch George and Morris deeply satisfied that you are keeping our was held on 12 December 2019 at HRI’s Posa National Foundation Eliza Street headquarters and included for Medical Research researchers in the labs, where they can Home789 make the discoveries of today that will a tour of the laboratories. This event is Innovation to thank patrons for their generosity and JJ’s Waste & become the treatments of tomorrow. Peter and Barbara honour those who have left a bequest to Recycling and In Thank you. Hoadley HRI throughout the year. The 2019 brunch Vitro Technologies Sydney Local Health was preceded by a memorial service James N Kirby District dedicated to Steven Posa and attended Foundation by many of his family and friends. Tony Clarke John and Sarah Batistich Vertex Rail RICHARD WYLIE Director, Fundraising John Fairfax The Wenkart Foundation and Brand Leon Ball
24 2019 Heart Research Institute Annual Review Notable Awards
NOTABLE 2019 AWARDS
PROFESSOR ASSOCIATE ASSOCIATE SHAUN PROFESSOR PROFESSOR JACKSON SIMONE JOHN SCHOENWAELDER O’SULLIVAN
Professor Shaun Jackson, Director of Associate Professor Simone Schoenwaelder Associate Professor John O’Sullivan, leader Cardiovascular Research at HRI as well as of the Thrombosis Group was awarded the of the Cardiometabolic Disease Group, was leader of the Thrombosis Group, was invited title of Associate Professor (Conjoint) in the awarded a Cardiovascular Clinician Scientist to speak at the 25-year celebratory luncheon Discipline of Physiology, the School of Medical Grant by the NSW Government and also for the Victorian Premier’s Awards for Sciences, the Faculty of Medicine and Health, received the Sydney Local Health District Health and Medical Research. These awards The University of Sydney. Early-Mid Career Researcher Award. recognise distinguished researchers for their lifelong achievements and contribution to breakthroughs in cardiovascular disease. Professor Jackson was the first winner of this award 25 years ago.
PROFESSOR DISTINGUISHED DR LINING DAVID PROFESSOR (ARNOLD) JU CELERMAJER AO ANNEMARIE HENNESSY AM
Professor David Celermajer, the HRI’s Professor Annemarie Hennessy AM, leader Postdoctoral Fellow with Thrombosis Group Clinical Director, was bestowed with the of the Vascular Immunology Group, was Dr Lining (Arnold) Ju, now appointed to the inaugural Ruthven Blackburn Medal for named Distinguished Professor by Western Faculty of Engineering at The University of Excellence in Clinical Research, for his Sydney University. This highly prestigious Sydney, was awarded the NSW Ministerial lifetime contribution to clinical research. honour is awarded to researchers who have Award for Rising Stars in Cardiovascular international influence within their field and Research. This prestigious award recognises The award recognises his achievements a commitment to excellence, have made early to mid-career researchers who have in cardiovascular health, particularly his a difference to the Australian region and demonstrated excellence in research important discovery of the damaging effects the world, and continue to demonstrate achievement and also the potential to of passive smoking on the vascular health intellectual leadership and are highly become a future leader in their field. of children. This breakthrough contributed recognised in their field. to policy change in several countries. The award was announced by The Hon Brad In 2019, Professor Hennessy was also Hazzard MP, Minister for Health and Minister made Honorary Fellow by The Royal for Medical Research at the 2019 NSW Australian and New Zealand College Cardiovascular Research Network (CVRN) of Obstetricians and Gynaecologists Showcase and Awards Ceremony. (RANZCOG). Dr Ju also received the Discovery Early Career Researcher Award (DECRA) from the Australian Research Council and Best Download a full list of HRI awards: Presentation Award at the NIH Cardiovascular www.hri.org.au/about/reports BioEngineering Conference in 2019.
25 2019 Heart Research Institute Annual Review Board of Govenors
L-R: Drs Melissa Farnham and Jessica Maclean
26 2019 Heart Research Institute Annual Review Board of Governors
BOARD OF GOVERNORS
The Board of Governors is chaired by Professor Len Kritharides and CHAIRMAN comprises deans from medical schools, nominees from The Sydney Professor Len Kritharides Local Health District, affiliates of The University of Sydney, leaders MBBS, PhD, FRACP, FCSANZ, from the corporate sector, and the Director of Cardiovascular FAHA, FESC, FACC Research of the Heart Research Institute. The Board is responsible for the governance of the Heart Research Institute. It approves and monitors budgets and scientific progress. Members are balanced to represent the corporate and scientific community. The majority of the Board positions are available to be filled via election by the members of the incorporated company, the Heart Research Institute Ltd. To read the bios of our Board Members: www.hri.org.au/about/ meet-the-board
Dr Teresa Anderson AM, FIPAA Mr Rod Halstead B App Science (Speech Pathology), PhD LLB (Syd), LLM (Lon), FAICD
The Hon Bruce Baird Professor Shaun Jackson BA (Syd), MBA (Melb) MBBS (Hons), BMedSci (Hons), PhD
Mr John Batistich Mr Richard Rassi BBus, MMGT, GAICD BCom, FCA, GAICD
Mrs Sandra Boswell Professor Stephen Simpson BEc, DipEd (Secondary), AC, FAA, FRS Registered Tax Agent
Professor Andrew Boyle Honorary Solicitor Ms Trish Paton MBBS (Hons), FRACP, PhD BA, LLB
INTERNATIONAL BOARD OF GOVERNORS
Mr Tony Pollitt (Chair) Dr Stephen Hollings BEcon (MACQ), MBA (UNE), FCA BA (Hons), PhD, FAICD
Mr John Batistich Mr Stephen Moodey BBus, MMGT, GAICD BBus, MBA, CPA
Mr Alan Caton OBE Mr Adrian Phillips BA (Hons)
Mrs Kerry Cunningham Mrs Elena Pintado BCom
27 HEART RESEARCH INSTITUTE Annual Report 2019
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