2018 Heart Research Institute Annual Review

Accelerating Research Tomorrow’s cure Tomorrow’s Today’s research Today’s 2018 Heart Research Institute Annual Review

Hello Future Accelerating 2018 Heart Research Institute Annual Review Research

ACCELERATING Discoveries into therapies

Knowledge into prevention

Breakthroughs into cures

Students into leaders

Collaborations into partnerships 4 2018 Heart Research Institute Annual Review

Inspiring Leaders 2018 Heart Research Institute Annual Review

CONTENTS

06 HRI in 2018

08 Chairman’s Report 2018

10 Director of Cardiovascular Research Report

12 2018 Research and Media Highlights

16 Applied Materials Group

18 Atherosclerosis and Vascular Remodelling Group

20 Cardiac Imaging Group

22 Cardiometabolic Disease Group

24 Cardiovascular Medical Devices Group

26 Cell Therapeutics Group

28 Clinical Research Group

30 Haematology Research Group

32 Heart Rhythm and Stroke Prevention Group

34 High Blood Pressure Group

36 Thrombosis Group

38 Vascular Complications Group

40 Vascular Immunology Group

42 Inflammation and Fibrosis Research

44 PhD Students

45 Select Prizes and Awards

46 Select Conferences and Presentations

50 Select Publications

56 Board of Governors

59 International Board of Governors

60 Members of the Institute

62 Fundraising Report

66 Operations Report 6 2018 Heart Research Institute Annual Review

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. 20 18

SHORT TERM LONG TERM

The major short-term focus of our research There are four long-term objectives is to understand the development and for our research: progression of atherothrombotic conditions • To investigate mechanisms in which the arteries are narrowed and contributing to the pathogenesis restricted due to a build-up of fatty of cardiovascular disease. deposits. • To develop new ways to detect symptoms of cardiovascular disease This is being achieved via scientific and before it leads to clinical problems. clinical research work conducted by the • To develop new treatments that can scientific groups that make up the HRI, reverse the development of heart from basic biomedical discovery work, disease. drug discovery and development, and • To prevent individuals developing devices and device improvement, to cardiovascular disease in the future. clinical trials and clinical initiatives. HRI in 2018

Locations 60+ COLLABORATIONS ACROSS 25 COUNTRIES • 7 Eliza Street, Newtown • Charles Perkins Centre, The University of Sydney

Chairman Professor Len Kritharides

Director of Cardiovascular Research Professor Shaun Jackson

Chief Executive Officer Dr Stephen Hollings

Deputy Director Research Strategy Professor Ben Freedman

Acting Scientific Director Emeritus Professor Carolyn Geczy

Clinical Director Professor David Celermajer 2018 GRANT INCOME 2018 CITATIONS BY FUNDING BODY Associate Directors of Research Management and Education Dr Mary Kavurma (Eliza St) 172 Assoc Professor Simone Schoenwaelder (Charles Perkins Centre)

13 Scientific Groups $1,361,973 $25,488 • Applied Materials (5.35%) (0.10%) 2018 PERSONNEL • Atherosclerosis and Vascular National Health Australian Remodelling and Medical Research • Cardiac Imaging Research Council Council (ARC) 250+ • Cardiometabolic Disease (NHMRC) • Cardiovascular Medical Devices • Cell Therapeutics • Clinical Research • Haematology Research • Heart Rhythm and Stroke Prevention 2018 HRI INCOME • High Blood Pressure • Thrombosis $75,000 $1,024,443 • Vascular Complications (0.29%) (4.03%) • Vascular Immunology National Heart NSW Government Foundation (NHF) (MRSP) Our Partnerships • Charles Perkins Centre, The University of Sydney • Sydney Local Health District and Sydney Health Partners - Royal Prince Alfred Hospital - Sydney Research $2,083,654 $15,000 $20,854,773 Australian Business Number (8.19%) (0.06%) 41 003 209 952 Other Commercial (81.98%) funding TOTAL: $25,440,331 Donations 8 2018 Heart Research Institute Annual Review

Chairman’s Report 2018

PROFESSOR LEN KRITHARIDES

CROSSING DIVIDES AND prevention, the better application of Clinical research provides relevance, BUILDING BRIDGES established therapies and the identification defining clinical problems and establishing Heart attacks and strokes remain the of new treatments. Community awareness the efficacy and impact of treatments. The commonest cause of mortality and of cardiovascular disease as a contemporary combination of the two, moving from bench morbidity in the Australian population, and cause of premature death and disability to bedside and from bedside to bench, is very in developing countries they are increasing is remarkably low – making our ability to powerful. It is for this reason that since its at an alarming rate. The incidence is deliver optimal prevention and treatment inception, the HRI has always crossed the fuelled by our ageing population and the to the community challenging. divide between basic science and clinical increasing prevalence of diabetes and research, closely linked at its foundation obesity. Combating heart disease and stroke Laboratory science provides mechanistic with the Department of Cardiology at – commonly referred to as cardiovascular understanding – how and why things happen RPAH. Current clinician scientists at the disease – requires increased efforts in – in the great engine room of discovery. HRI include cardiologists (Professors Chairman’s Report 2018

David Celermajer and Ben Freedman, and New Zealand, industry, and NSW Dr Lining (Arnold) Ju an ATVB Career Associate Professor Sanjay Patel and Health. The diversity of external funding Development Award, Dr Steve Wise was Dr John O’Sullivan), renal and obstetric sources reflects the diverse portfolio of awarded the Marshall and Warren Award physician Professor Annemarie Hennessy, research undertaken by HRI scientists – for Most Innovative Project Grant by the haematologist Dr Freda Passam, radiologist from bench to bedside. The contribution NHMRC, and Professor Shaun Jackson Professor Stuart Grieve, and our Director of NSW Health in directly supporting received the CVRN 2018 Ministerial Award of Cardiovascular Research Professor cardiovascular research is especially for Cardiovascular Research Excellence, Shaun Jackson. The ability to cross-appoint notable. It reflects a major change in the presented by The Honourable Brad Hazzard clinicians to RPAH and to the HRI is critical research landscape in NSW, providing MP, NSW Minister for Health and Minister to the ongoing success of the HRI, and career and project support for aspiring for Medical Research. has been strongly supported by the Chief scientists and clinician-scientists, and is The ability of our scientists to undertake Executive of the Sydney Local Health proving critical for the sustainability of such excellent work requires outstanding District, Dr Teresa Anderson. cardiovascular research in NSW. infrastructure and administrative support. The HRI crosses another divide – the divide The partnership with the NSW Government The scientific leadership of the HRI, led by between biological science and chemical was most emphatically demonstrated with Professors Shaun Jackson, Carolyn Geczy discovery. NHMRC-funded collaborative the announcement in 2018 of the NSW and Ben Freedman, the management team research between Professor Shaun Cardiovascular Research Capacity Building of the HRI led by our CEO Dr Stephen Jackson and Professor Richard Payne Grants Program worth $150 million over Hollings, our fundraising team led by from the Department of Chemistry at The 10 years. This major commitment by the Richard Wylie, our human resources lead University of Sydney is discovering new Berejiklian Government, a first for Australia, Elissa Dwyer, and our committed Board chemicals to inhibit the formation of blood represented the culmination of another of Governors and International Trustees/ clots, which may have implications for the collaboration – between the HRI, the Victor Directors deserve our enduring gratitude treatment of critical events such as stroke. Chang Cardiac Research Institute and the and sincere thanks. Such research requires internationally NSW Cardiovascular Research Network This report began by referring to crossing competitive expertise on both fronts – (CVRN) of the Heart Foundation. This peer- divides and building bridges, and I hope biology and chemistry – and an environment reviewed funding pool will be open to all I have given an indication of the importance that encourages collaboration. cardiovascular researchers in NSW, and of partnerships in achieving great science. represents a major increase in the total I would like to finish by acknowledging what is for the HRI its most enduring “Our scientific achievements are fundamentally partnership – the partnership with you, its members and donors. Our scientific also the achievements of our supporters, and it is achievements are fundamentally also important that we can share the achievements of the achievements of our supporters, and it is important that we can share the our scientists with you.” achievements of our scientists with you. The HRI has always been strongly supported by the enormous goodwill of Other leading scientists at the HRI whose pool of funds available for urgently needed the general community, and that support work straddles biology and bioengineering, cardiovascular research in NSW. The has never been more valued. biochemistry and biomaterials science at HRI should take particular pride in The University of Sydney include Drs Anna this achievement, given the critical role Waterhouse, John O’Sullivan, Steve Wise, Professor Shaun Jackson, Professor Freda Passam, Ashish Misra and Lining Ben Freedman and Dr Stephen Hollings (Arnold) Ju, Associate Professor Simone had in initiating and bringing this Schoenwalder and Professor Paul Pilowsky. funding program to fruition.

The third collaboration underpinning the Our scientists received many notable work of the HRI is that with funding bodies. personal awards in 2018. These included In 2018, HRI research was funded by Drs Anna Waterhouse and John O’Sullivan PROFESSOR LEN competitive peer-reviewed grants from being awarded Catalyst awards, Anna also KRITHARIDES the NHMRC, The National Heart Foundation, receiving an ASBTE Young Investigator The Australian Research Council, award and John also receiving a NSW MBBS PhD FRACP FCSANZ FAHA FESC FACC philanthropic trusts such as Perpetual, Clinician Scientist award. Dr Freda Passam Chairman, Board of Governors, Ramaciotti, the Cardiac Society of Australia received a MCR Accelerator Award, Heart Research Institute 10 2018 Heart Research Institute Annual Review

Director of Cardiovascular Research Report

PROFESSOR SHAUN JACKSON

Our researchers at the HRI are on a engagement with our clinical colleagues, and Cell Therapeutics and Clinical Research relentless journey of discovery, constantly of course, the inspiration and relevance that Groups, respectively, designed and laying the groundwork for our next major comes from understanding the medical needs executed a clinical study of 80 patients breakthrough. The quicker we can cover of patients. At the HRI we are fortunate to with recent acute coronary disease. These the ground to arrive at our destination, have all these elements, and we continue to studies, published in the journal JACC – the sooner the benefits of this work can work hard to create an optimal environment in Cardiovascular Imaging (a journal of the be applied to the community. However, which innovation and discovery can flourish. It American College of Cardiology), have painstaking research is never quick or easy, is my pleasure to update you on our progress provided important clinical evidence that often requiring many decades to translate throughout 2018 to achieve our mission. the repurposing of colchicine – a common, important new findings into the next major relatively safe and low-cost drug used advance in medical care. It is a long and to treat gout – can stabilise the coronary patient journey requiring very talented and ACHIEVEMENTS plaque. With potential for this drug to dedicated individuals. I’m pleased to report that 2018 has been become a third pillar in management of another year of tremendous achievements. coronary artery disease, these findings We have been fortunate to recruit great new Our researchers have secured more than could have wide-reaching impact for the talent to the HRI over the last few years, 20 competitive research grants and medical management of coronary artery however hard work and scientific brilliance fellowships, including highly prestigious disease patients. alone is not always enough for success in awards from the National Health and modern day research. We also need a world- Separate studies by researchers from the Medical Research Council (NHMRC) and class research environment. The enablers of Thrombosis Group, championed by Dr Lining Australian Research Council (ARC). world-class research are many, and include (Arnold) Ju, have published groundbreaking first-class research facilities, cutting-edge Our research continues to be published in findings identifying what differentiates technologies, inspiring scientific role models, prestigious medical and scientific journals. normal blood clotting from pathological world-class collaborators and thought- In 2018, Associate Professor Sanjay Patel blood clotting. The answer to this long-asked provoking colleagues, close proximity and and Professor David Celermajer from the question lies in the physical or biomechanical forces imposed by changes in blood flow, which the team identified as a major player leading to increased clotting seen in diabetic patients. These studies, published in the journal Nature Communications, also provided scientific evidence for a potential way to block this pathological blood clotting, a finding with major implications for the millions of individuals with diabetes. The Vascular Immunology Group, led by Professor Annemarie Hennessy, published groundbreaking studies that represent the culmination of 12 years of collaborative work between the University of Massachusetts and the Beth Israel Deaconess Medical Centre in the USA, as well as the University of Western Sydney and the HRI, to identify a safe target to stop the progression of preeclampsia. These studies used state- of-the-art RNA interference technology to reduce the levels of an enzyme (sFLT1) implicated in this condition, and were published in the prestigious journal Nature Biotechnology, paving the way for future research to optimise this approach, with successful translation holding the ability to L-R: Executive team: Emeritus Professor Carolyn Geczy, Elissa Dwyer, transform the treatment of preeclampsia. Dr Stephen Hollings, Professor Shaun Jackson, Richard Wylie Director of Cardiovascular Research Report

"The quicker we can cover the ground to arrive at our destination, the sooner the benefits of this work can be applied to the community."

Our scientists also had many notable we have established one of Australia’s Quite simply, without the efforts of our personal achievements in 2018, which are leading cardiovascular research events, fundraising team and our incredibly loyal noted by Professor Len Kritharides in his the Sydney Cardiovascular Symposium. donors, we would not be able to continue Chairman’s Report (see p8). The 2018 meeting was a huge success, our groundbreaking research efforts. I am with over 300 registrants and a stellar truly indebted to all who support us. list of local, national and international CROSS-INSTITUTE COLLABORATION speakers who explored the impact of the LEADS TO $150M FROM THE NSW obesity epidemic and its consequences OUR LEADERSHIP TEAM GOVERNMENT on cardiovascular health. For the Institute, 2018 was a year of hard I am delighted to report the establishment work and continued transformation. I would The Honourable Dominic Perrottet MP, of a bold new initiative in NSW, termed particularly like to thank our hardworking NSW Treasurer and Minister for Industrial the Cardiovascular Research Capacity management team, including Dr Stephen Relations officially opened the Symposium, Building Program. This new initiative was Hollings (Chief Executive Officer), Professor while The Honourable Brad Hazzard MP, NSW led by the HRI, in partnership with the Ben Freedman (Deputy Director Research Minister for Health and Minister for Medical Victor Chang Cardiac Research Institute Strategy), Emeritus Professor Carolyn Geczy Research, presented the Symposium’s Early (VCCRI), and received the full support of (Acting Scientific Director), Mr Richard Wylie and Mid-Career Researcher Awards and the the NSW cardiovascular community under (Director, Fundraising and Brand), Ms Elissa Rising Star Award. the auspices of the Cardiovascular Research Dwyer (Director, Human Resources) and Network (CVRN). This collaboration between International speakers included Professor Ms Vania Dauner (Executive Assistant), for HRI and the VCCRI was unique, marking Ed Fisher (New York University), Professor their major contributions and dedication to the first time the NSW cardiovascular Darrel Francis (Imperial College London), the Institute and its researchers throughout medical research community has come to Associate Professor Katey Rayner (Ottawa the year. I’d also like to recognise and government with one voice and one vision. University) and Professor Jonathan Cohen thank our Associate Directors of Research The result is an innovative capacity building (UT Southwestern), who also delivered the Management and Education, Dr Mary program that aims to attract and retain the iconic Princesses’ Lecture. National speakers Kavurma and Associate Professor Simone very best cardiovascular researchers here in included leading researchers from the Schoenwaelder for their hard work and NSW, with the ultimate goal of making NSW Garvan Institute of Medical Research, dedication. I am extremely fortunate to the Premier State for Heart Health. The George Institute for Global Health, have such dedicated individuals and a Baker Institute, University of Adelaide, cohesive management team who have The NSW Government announced this new University of Melbourne, The University worked tirelessly throughout the year. initiative in June 2018 and have committed of Sydney, VCCRI and HRI. $150 million over the next 10 years to fight I’d also like to thank our Operations team the resurgence of cardiovascular diseases. for supporting our scientists so effectively I wish to thank the NSW Premier Gladys in 2018. LAUNCH OF THE HRI/CENTENARY Berejiklian, Treasurer and Minister for INSTITUTE CARDIOVASCULAR Finally, and most importantly, I’d like to Industrial Relations Dominic Perrottet and SEMINAR SERIES thank the HRI’s wonderful donors who Minister for Health and Minister for Medical Partnering with our research neighbours make so much of our work possible. Your Research Brad Hazzard for their vision and at the Centenary Institute, HRI launched support keeps our researchers in the labs, support of this important initiative. I also a collaborative seminar program in 2018, where they can make the breakthroughs want to thank my colleagues at the HRI, bringing together prominent international that will hopefully become the treatments particularly Dr Stephen Hollings, Professor and national, external speakers, to present of tomorrow. Your generosity is enormously Ben Freedman and Mr Richard Wylie for their cutting-edge cardiovascular disease appreciated by all of us at HRI. Thank you. their hard work and unwavering support research to the NSW community. Hosted at of this initiative, as well as Mr Mathew the Charles Perkins Centre, The University Grounds, Professor Bob Graham and Ms Britt of Sydney, seminar speakers included Granath from the VCCRI, for their fabulous notable scientists, biomedical engineers collegiality, friendship and support. and clinicians with expertise in It was a great team effort! cardiovascular research.

NSW CARDIOVASCULAR SYMPOSIUM FUNDRAISING The HRI has played a leading role in bringing PROFESSOR SHAUN JACKSON Fundraising and philanthropy plays a vital together cardiovascular researchers across role at the HRI, and a full report of our MBBS (Hons) BMedSci (Hons) PhD the state. In partnership with the VCCRI, activities in this area is available on p62. Director of Cardiovascular Research 12 2018 Heart Research Institute Annual Review

2018 Research and Media Highlights

New drug hope to target Predicting diabetes high blood pressure before it strikes Appeared on Channel 9 News, January 2018 Appeared on Channel 7 News, February 2018

The High Blood Pressure Group has uncovered In a world-first, the Cardiometabolic Disease a brain chemical instrumental in triggering Group led by Dr John O’Sullivan has developed hypertension, the so-called silent killer a simple test to predict diabetes more than a responsible for the deaths of thousands of decade before it strikes. Australians each year. The blood test is for a molecule found in liver The best early indicator of hypertension is fat that puts carriers on the path to diabetes. excessive brain activity in the part of the brain It is the first time we have been that controls blood vessel constriction and able to predict with certainty who will relaxation. The Group investigated the role develop the disease. of the neurotransmitter PACAP in causing this increased activity in people affected by “The earlier you can detect it, the earlier obstructive sleep apnoea. you can intervene. And the earlier you intervene, the more success you’ll have The team discovered that by blocking PACAP, to reverse diabetes,” says Dr O’Sullivan. they were able to dampen over-active neurons, This breakthrough could help ease the suggesting PACAP receptors are a novel impending diabetes epidemic. target for preventing the progression of over-active brain activity to hypertension. Full media report and video: https://bit.ly/2IsHajQ Full media report and video: https://bit.ly/2Pf6ydn

“The earlier you can detect it, the earlier you can intervene." 2018 Research and Media Highlights

L-R: Prof Shaun Jackson, The Hon Brad Hazzard MP Professor Shaun Jackson received Ministerial Award for CV Research Excellence Heart of silk At the NSW Cardiovascular Research Network’s annual State Appeared on Channel 9 News, March 2018 of the Heart Showcase, Professor Shaun Jackson received the Ministerial Award for Cardiovascular Research Excellence, presented by The Honourable Brad Hazzard MP, NSW Minister for Health and Minister for Medical Research. As a clinician scientist and leading international authority in the thrombosis and haemostasis field, Professor Jackson’s research into blood clotting has contributed significantly to international cardiovascular scientific and medical knowledge. His work has led to the development of a novel drug – a “super” aspirin with greater efficacy but less bleeding risk – that could transform the treatment of stroke and heart attack.

Award-winning Vascular Immunology Group

The team from the Vascular Immunology Group, Professors The Applied Materials Group led by Annemarie Hennessy and Angela Makris, was awarded Dr Steven Wise has built and tested silk blood Academic Unit Status at the South Western Sydney Local vessels, and discovered they’re more effective Health District. In 2018, Professor Hennessy was also awarded and better tolerated than synthetic materials the title of Distinguished Professor from Western Sydney currently used in Australian hospitals. University, and in recognition of her contribution to local education and research, was one of ten faces of Campbelltown, If a person’s own vein cannot be used in Sydney to feature as part of a city mural campaign. Work by an operation such as a heart bypass, then the Vascular Immunology Group on a gene therapy model that synthetic materials are used instead. may advance treatment of preeclampsia was also featured in “The synthetic alternatives are Dacron, several media outlets, including the Worcester, Massachusetts used in drink bottles, and GoreTex, used in Telegram on 28 November 2018. raincoats, but these materials are very foreign to the body and cause clots,” Dr Wise says. “In fact, when it comes to a heart or Collaboration leg bypass, they fail uniformly and are only used in emergency situations.” results in $150

Using silk worm cocoons and an million boost to electrospinner, the Applied Materials Group research funding can create silk grafts that the body re-models naturally, thus avoiding the need to use The Heart Research Institute and the Victor Chang synthetic materials. Cardiac Research Institute, supported by the entire NSW cardiovascular community, oversaw the successful proposal to With a silk alternative, the coronary the NSW State Government for the $150 million Cardiovascular bypass option will be available to more Research Capacity Building Program. This collaboration, driven patients without the need to use healthy by Professor Shaun Jackson and Professor Bob Graham, replacement vessels. marks the first time the NSW cardiovascular medical research community has come to government successfully with one Full media report and video: voice and one vision. The Program will confirm NSW as the https://bit.ly/2vaXNaY premier state for cardiovascular health. 14 2018 Heart Research Institute Annual Review

Super-charged Biomaterial heart nanoparticles poised patch breathes to change the drug life into dead tissue delivery landscape Appeared on Channel 9 News, April 2018

Appeared on Channel 7 News, March 2018

Dr Miguel Santos and the Applied Materials A highly promising innovation from the Applied Group have engineered multifunctional Materials Group is a biomaterial patch that nanoparticles that can effectively work allows stem cells to repair damaged hearts as ‘nanocarriers’, hauling a wide range of more effectively. molecules, including drugs or genetic material, to exactly where they need to go in the body. Stem cells hold great promise in the treatment of heart disease, but stem cell therapies A single nanoparticle may carry a cocktail of to date have been limited by the failure of molecules made of therapeutic agents like injected cells to firmly graft onto damaged drugs, proteins or genetic materials, as well tissue following transplantation. as targeting and imaging agents all in the same nano structure. By combining the As an alternative to injected cells, the team therapeutic agents together with molecules investigated growing the cells on a compatible that recognise the targeted cells or organs, biomaterial patch, which is then implanted in the treatment dose can be significantly the body. In studies the patch proved to be lowered, reducing also the associated side a perfect scaffold for stem cells to grow on. effects as healthy cells are less affected. “Results like ours help overcome translational “The potential for these nanoparticles to challenges and unlock the tissue regenerative change the drug delivery landscape is huge. potential behind stem cells for the treatment The possible applications range from improved of practically any disease in the human body,” ways to treat heart disease, cancer and says Dr Richard Tan, lead researcher. Alzheimer’s, through to more efficient gene therapies,” says Dr Santos. Full media report and video: https://bit.ly/2DK2CwA Full media report and video: https://bit.ly/2Pfzz8S

“Results like ours help overcome translational challenges and unlock the tissue regenerative potential behind stem cells for the treatment of practically any disease in the human body.” 2018 Research and Media Highlights

Special awards presented at Illuminate At HRI’s Awards for Excellence dinner, Illuminate, the Sydney Local Health District (SLHD) Mentor of the Year Award was presented to Emeritus Professor Blood clot breakthrough Carolyn Geczy (pictured with Dr Teresa for people with diabetes Anderson, Chief Executive of SLHD) for her dedication in nurturing, developing Appeared on Channel 7 News, May 2018 and mentoring early-career researchers, and in providing support and direction on grant applications and direction of research to HRI scientists. The HRI Lifetime Achievement Award was presented to Professor Wendy Jessup (bottom), for her significant contributions to HRI over the past 30 years, in roles ranging from research Group Leader to Deputy Director, Board member, and positions on the HRI Scientific Advisory Committee and other committees.

Collaboration reveals atrial fibrillation discovery

A collaboration between the Heart Rhythm and Stroke Prevention Group at HRI and the University of Auckland researchers revealed for the first time that Mãori and Pacific people develop atrial fibrillation (AF) – a key risk factor for stroke – a decade earlier than other New Zealanders. The work has important implications for heart testing guidelines in New Zealand as it suggests that Mãori and Pacific people should be tested for AF earlier than the current recommended age of 65. The research also has implications for Australian Indigenous Cardiovascular disease is the leading cause of people, who also develop AF earlier than other Australians. death for people with diabetes – who are also four times more likely to suffer a heart attack or stroke than those without diabetes. In a medical breakthrough, the Thrombosis Group led by Professor Shaun Jackson has uncovered why common blood thinners used to protect millions worldwide from life- threatening blood clots don’t work as well for people with diabetes.

A drug the team is developing has been found to target this new pathway of blood clotting, L-R: Prof Bob Graham, Dr Richard Tan, The Hon and appears to be effective in preventing Brad Hazzard MP, Prof Shaun Jackson disease-forming clots in people with diabetes. 2018 Sydney Cardiovascular “If it can be used successfully to treat people with diabetes, we’ll be protecting many Symposium of those in our community that are most vulnerable to heart disease and stroke,” The Heart Research Institute and the Victor Chang Cardiac says Professor Jackson. Research Institute formally partnered for the second time to host the 2018 Sydney Cardiovascular Symposium, 5–7 Full media report and video: December at the Charles Perkins Centre, The University https://bit.ly/2ZiASbH of Sydney. The theme Cardiovascular Disease in the Era of Obesity and Diabetes: Challenges and New Frontiers explored the impact of the obesity epidemic and its consequences on cardiovascular health, from bench to bedside and back again. The Honourable Dominic Perrottet MP, NSW Treasurer and Minister for Industrial Relations officially opened the “If it can be used successfully to treat people Symposium, while The Honourable Brad Hazzard MP, NSW with diabetes, we’ll be protecting many Minister for Health and Medical Research, presented the of those in our community that are most Symposium’s Early and Mid-Career Researcher Awards and the Rising Star Award. This successful event was managed by vulnerable to heart disease and stroke.” the HRI team led by Drs Mary Kavurma and John O’Sullivan. 16 2018 Heart Research Institute Annual Review

Applied Materials Group

RESEARCH TEAM PRAVEESUDA (JOY) MICHAEL DR STEVEN WISE PhD Student Group Leader DR BEHNAM AKHAVAN BSc (Hons 1) PhD University Medal Visiting Scientist SIDRA NAZIR Visiting Student ALEXANDER BENN OUR MISSION Honours Student BRYCE REEVES The mission of the Applied Materials Summer Student Group is to develop the next generation of ALEX CHAN translatable bioactive materials – materials PhD Student/Research Officer MAIRI ROBERTSON that can bond to living tissues – and provide NZ Summer Student JUI CHIEN HUNG better treatment options for people with Research Assistant DR MIGUEL SANTOS cardiovascular disease. We work with Postdoctoral Scientist exciting new classes of biomaterials, NICHOLAS KONDAL including naturally derived proteins and NZ Summer Student CALLUM STEWART polymers and the latest in synthetically Visiting Scientist BOB LEE produced plasma surfaces and products. PhD Student DR RICHARD TAN The Group aims to engineer and optimise PhD Student/Research Officer these materials to be therapeutically useful RORY MCKAY in the treatment of vascular disease and NZ Summer Student ERIC YANG PhD Student more broadly in tissue repair. Applied Materials Group

OUR IMPACT injury to switch into a reparative state, fast-tracking the The materials currently available for vascular repair healing response. We have successfully demonstrated are fundamentally incompatible with the tissues they that the performance of patches and vascular grafts seek to repair. Metal alloys like stainless steel, and the is greatly improved with this approach, with significant same plastics used in Gore-Tex jackets and drinking implications for the development of better materials for straws are in wide use, relying on technology that has vascular repair. Our latest research is locally delivering not evolved considerably for several decades. Discovery anti-inflammatory agents to the site of vessel injury in of new materials that could be used clinically would order to fast-track the healing response. have a significant impact on the lives of patients.

RESEARCH PROJECTS Silk-based biomaterials for vascular repair In partnership with Dr Jelena-Rnjak Kovacina at the University of New South Wales, the Applied Materials Group successfully demonstrated that silk is a very promising material for building new synthetic blood vessels. Silk fibroin is a versatile natural polymer with “The benefits will be felt remarkable mechanical properties. Purified silk is across biomaterials, tissue extremely well tolerated in the body, demonstrating a very low inflammatory response. The biodegradability engineering and vascular and elasticity of silk can also be controlled during biology fields, as well as scaffold manufacture, making it an exciting biomaterial. During 2018, we completed a long-term study of the contribute to Australia’s place biological response to implanted silk grafts, showing as a leader in these areas.” that they were extremely well tolerated, integrating with the native tissue over time. Changing the physical properties of the silk, including the porosity, can further improve tissue integration. The project has been awarded NHMRC project funding to continue pre-clinical testing in 2019. RESEARCH HIGHLIGHTS There is significant potential for generating lab-based Prolonging the life of stem cells models of human blood vessels, to study underlying Stem cells hold great promise in the treatment of biology and pathology. Replicating appropriate pressure heart failure and heart disease. However, stem cell and flow conduits coupled with sustained survival of therapies to date have been limited by the failure key vascular cell types is critical to the success of this of injected cells to firmly graft onto damaged tissue. approach and has been largely lacking from the field. To be therapeutically useful, the lifetime of stem cells delivered to injured tissue must be extended. Working with corporate partner Codex Research, The Applied Material Group has developed new we are developing an in vitro blood vessel model biomaterial patches that provide the physical and that will mimic arterial conditions by, for the first biological signals required by these cells to attach time, incorporating vascular cells and silk conduits and grow. Screening through an array of scaffold as scaffolds. This approach aims to overcome the materials, we have identified a recipe that increases limitations of simplistic 2D cell cultures, the long the life-time of tissue repairing stems cells from maturation times of fully tissue-engineered vessels, one hour to four days in a pre-clinical model. and resource-intensive animal models. It will offer a solution for modelling of native vessel processes in New classes of bioactive materials regulate the lab that would be more appropriate for pre-clinical the inflammatory response drug and device development, and in the long term, A core interest of the Applied Materials Group is tissue replacement. The project has just been awarded understanding the foreign body response to implanted ARC Linkage Project funding to uniquely bring together materials. We have developed a new material that industry expertise in control systems and electronics actively signals the body to control the inflammatory with the significant experience of our research team response to implants. This achievement is particularly in biomaterials engineering and vascular biology to relevant to diseases of the blood vessels, where drive a fundamental advancement of in vitro blood inflammation and the body’s own immune response vessel modelling. are critical drivers of disease progression. These newly developed materials can direct the behaviour The benefits will be felt across biomaterials, tissue of the body’s early response system, signaling to engineering and vascular biology fields, as well as macrophages (inflammatory cells) at the site of the contribute to Australia’s place as a leader in these areas. 18 2018 Heart Research Institute Annual Review

Atherosclerosis and Vascular Remodelling Group

OUR MISSION OUR IMPACT Factors and regulators of smooth muscle The mission of the Atherosclerosis Cardiovascular disease is the main cause of cells and macrophages in progression and Vascular Remodelling Group is to death globally, accounting for approximately of atherosclerosis identify and gain insights from the genetic one third of all deaths. Currently available Atherosclerosis is a leading cause of death and molecular pathways involved in cardiovascular therapies are not universally worldwide. Atherosclerotic plaque or cardiovascular disorders, and exploit these effective and do not reverse the vascular atheroma consist of smooth muscle cells pathways to provide better therapeutic disease completely. Vascular diseases (SMCs) and macrophages in the malefactor options to eradicate cardiovascular disease. therefore place a heavy burden on the health lesion and are comprised of a lipid-laden care system. Our work to identify the factors core covered by a fibrous cap. Plaque rapture Our main objective is to broaden and signalling mechanisms involved in leads to thrombosis with dire consequences, understanding of the cellular and molecular cardiovascular disorders has the potential to such as myocardial infarction and stroke. mechanisms involved in blood vessel wall provide better options to treat and eradicate patterning and define the role of these SMCs and macrophages are key players in cardiovascular disease, thus decreasing its pathways in vascular abnormalities and atherogenesis. Although extensive research burden on society at large. complications, and then link these insights has been done in the past on atherosclerosis, to translational research to improve exactly how cells from normal blood vessel the prevention and treatment of human walls contribute to atherosclerotic plaques RESEARCH PROJECTS cardiovascular disease. is still far from clear. Our studies aim to The role of Notch signalling in discover the origin of the cells that make To this end, we employ a unique blending cardiovascular disease and normal blood vessels and how these cells of mouse models and cultured cells, as well related pathologies contribute to atherogenesis. Recently, our as human samples, with the aim of unveiling Notch has been comprehensively studied as studies established that very few SMCs the pathogenesis of cardiovascular diseases. a conciliator of cell-to-cell communication have the potential to migrate and proliferate that mediates cell fate decisions of Our ultimate goal is to prevent and reverse from the blood vessels and produce most progenitors. While Notch signalling has been vascular disease to prevent heart attack of the SMCs in atherosclerotic plaques. extensively studied in cell fate determination and stroke. The focus of our current studies is to at distinct development stages of mammalian identify new signalling molecules, factors cells as well as cancer stem cell progenitor and/or pharmacological inhibitors that can maintenance and renewal, the functional modulate SMC phenotypic switching and role of Notch signalling in vascular wall macrophage infiltration into the plaque patterning and cardiovascular disease is to change the plaque composition and not well understood. thereby promote plaque stability. By using advanced microscopic techniques, fate mapping approaches and single cell clonal analysis, we aim to study the role RESEARCH HIGHLIGHTS of Notch signalling in blood vessel wall In 2018, the Atherosclerosis and Vascular “Our ultimate goal is to patterning and maintenance of smooth Remodelling Group revealed how plaque prevent and reverse muscle cell progenitors in developing walls cells develop from blood vessels at the as well as disease of the vasculatures. Thus, molecular level: ‘rare’ muscle cells from vascular disease to we believe that the investigation of Notch artery walls migrate and proliferate into prevent heart attack signalling in vascular biology promises to atherosclerotic plaques. These findings shed be a very fruitful way forward to designing light on the complex mechanisms behind the and stroke.” new therapeutics. progression of atherosclerosis, and suggest a potential new therapeutic target. We published a high impact paper on this work in Nature Communications (Misra A et al, 2018), and this work was also highlighted by the prestigious F1000Research. AtherosclerosisHeart Rhythm and andVascular Stroke Remodelling Prevention Group

DR ASHISH MISRA Group Leader BSc MTech PhD

RESEARCH TEAM

ELAINA KELLAND NZ Summer Student

DR RAHUL KURUP PhD Student 20 2018 Heart Research Institute Annual Review

Cardiac Imaging Group

OUR MISSION Our long-term investment in imaging 4DCARE The mission of the Cardiac Imaging Group techniques that can better reflect real The largest prospective trial of 4D-flow is to improve patient outcomes using better pathology is paying off – in 2018 we acquired cardiac MRI ever, this is a multi-site study imaging and computational methods. the most detailed brain image ever at the aiming to validate the use of 4D-flow We focus on chronic disease across Mayo Clinic in Rochester, USA. Together centric protocol for routine clinical use. cardiovascular and neurovascular medicine. with GE Healthcare we are translating If successful, this would cut the imaging We believe that detecting and measuring these advances into our future studies. time for cardiac MRI by at least 50%, early disease while reversible is the key to while improving sensitivity and specificity. We were also the first to deploy both sustainable healthcare. accelerated 4D-flow MRI and multiband The Digital Heart Project Our research program covers several major diffusion imaging outside the factory for both The Digital Heart Project is a new project cardiovascular and neurovascular chronic GE Healthcare and Siemens. This research which builds on past group studies. It will diseases, with an emphasis on discovering has resulted in acceleration of these combine real world MRI, CT and ultrasounds fundamental biomarkers for application technologies into the clinic. data with clinical measures (ECG, blood in the clinic. Our program is a highly biomarkers, clinical outcomes) to build a multidisciplinary, translational research multidimensional digital representation effort involving engineers, basic scientists, RESEARCH PROJECTS of the heart (“digital heart”). psychologists, physicians, surgeons, Porcine stem cell heart failure study Imaging the effects of concussion project radiologists and imaging scientists. We (funded by NHMRC Project Grant) (funded by NHMRC Project Grant) collaborate with international and Australian This project combines cutting-edge stem The brain passport project leverages off researchers, and work closely with related cell biology, electrophysiology and our our world-best imaging capability in diffusion industries to continually advance medical imaging expertise to create a porcine imaging, with the global aim of visualising imaging and computational technology. model of heart failure. A collaboration the pathology in currently “invisible” brain across Sydney Health Partners, HRI/CPC, disorders such as concussion, surgical brain University of Washington and the Millennium injury, depression and brain dysfunction in Institute Westmead (CI James Choong cardiovascular/metabolic disorders such and Eddy Kizana), the project follows as hypertension, diabetes and obesity. our successful CVRN project on PDGF in a porcine heart failure model and will showcase the technological advances we have developed at HRI.

We have two overarching projects within the lab. In the heart, we aim to understand, measure and predict heart failure by using imaging to inform integrative, individualised heart models. Our neurovascular focus is on solving the problem of “seeing” brain damage secondary to cardiovascular disease and chronic injuries such as concussion or surgical injury. Depression is a special focus since it is the downstream result of many contributing causes of lifestyle, environment, injury and inherited risk.

OUR IMPACT Our Group is recognised as a leader in both heart, vascular and neuroimaging. In the past year, we consolidated and expanded our relationships with top institutions in the world, including the Mayo Clinic, Stanford, and UCLA. Cardiac Imaging Group

PROFESSOR STUART GRIEVE Group Leader DPhil (Oxon) MBBS (Hons) BSc (Hons) FRACP FCSANZ FRANZCR

RESEARCH TEAM

DR MATHEUS CARELLI DR JASON QUIN JENNY CHIANG Researcher/Cardiothoracic Registrar PhD Student Medical Student (MD project)

DR TEJAS CANCHI DR JARRAH SPENCER RUCHIRA JAYASENA Postdoctoral Researcher Researcher/Radiology Registrar Medical Student (MD project)

BEN ELIAS-INDJA DR KELLY STANTON NADIA LAHOUD MPhil Student PhD Student (Primary: David Celermajer) Medical Student (MD project)

DR SARGON GABRIEL DR MICHAEL STEVENS RUI NG Postdoctoral Researcher Postdoctoral Researcher (CRC) Medical Student (MD project)

DR MUSTAFA GOK DR SUJITHA THAVAPALACHANDRAN PHUONG NGUYEN Cardiac Fellow and Researcher PhD Student (Primary: James Choong) Medical Student (MD project)

DR VINEET GOOROLAY DR TOM WELTON CHARLES WALKER Researcher/Radiology Registrar Postdoctoral Researcher Medical Student (MD project)

DR SARAH HELLEWELL DR KEI WOLDENDORP ISABELLA ZAPPALA Postdoctoral Researcher Researcher/Cardiothoracic Registrar Medical Student (MD project)

DR MICHELLE LIM DR JAMES WOOD PhD Student (Primary: David Celermajer) PhD Student

MATTHEW LYON NICHOLAS BURN Research Assistant Medical Student (MD project) 22 2018 Heart Research Institute Annual Review

gain-of-function variants in metabolic Cardiometabolic pathways relevant for cardiovascular disease; and stable-isotope flux analysis. In our second theme, we use matched diets, Disease Group microbiome analysis, faecal and plasma metabolomics, and careful cardiovascular phenotyping, and have already identified OUR MISSION OUR IMPACT several novel pathways. The mission of the Cardiometabolic Cardiometabolic diseases, that lead to Disease Group is to improve the detection heart attacks and stroke, have exploded in RESEARCH PROJECTS and treatment of cardiovascular disease prevalence due to the 600 per cent increase Leveraging cardiac substrates to improve through the development of diagnostic in overweight and obesity rates over the cardiac energetics and outcomes in diabetic markers, predictors, and novel therapies last 40 years. Our work to enable earlier cardiomyopathy and HFpEF for cardiometabolic disorders. detection of cardiometabolic disorders, and It was recently demonstrated in three thus enable earlier intervention, could have We aim to discover new mechanisms in international clinical trials that the sodium a transformative impact on the health of cardiometabolic disease that we can target glucose co-transporter inhibitor (SGLT2i) the hundreds of millions of people around with novel therapeutic agents. We also aim class of medication unexpectedly improved Australia and the world who are at risk of to detect early markers of disease to guide heart failure (HF) morbidity and mortality diabetes and cardiovascular disease. timely intervention. Our research revolves in patients with diabetic cardiomyopathy around two major themes: In our first theme, we have developed (DbCM). Accumulating evidence suggests comprehensive resources with which 1. Uncovering the mechanism and that these agents provide “thrifty to make novel insights: our own diabetic identifying novel therapeutic targets substrates” that the HFpEF heart can use to cardiomyopathy clinic; cardiac MRI; in diabetic cardiomyopathy and Heart generate more ATP and improve function. metabolomics and genomics platforms; Failure preserved Ejection Fraction We have identified novel depleted cardiac in vivo murine models; an ex vivo perfusion (HFpEF). substrates using myocardial tissue from Langendorff model; iPSC-cardiomyocytes, heart failure patients and matched donor 2. Diet-microbiome-metabolism interactions including several lines carrying loss-or hearts (confirmed histopathologically in cardiovascular disease.

DR JOHN O’SULLIVAN Group Leader MD PhD MSc Cert Biostatistics (Harvard) FRCPI FAHA

RESEARCH TEAM

DR JACOB CAO Medical Intern RPA, Postdoctoral Scientist

JASON CHAMI Talented Students Program USYD

GABRIELLE FUSCO-ALLISON Research Assistant

JENNY GALLAGHER NZ Summer Student

DR YEN CHIN KOAY Postdoctoral Scientist

SWATHI KUMAR NZ Summer Student

JOHN PARK Honours Student

EVANGELINE PEARSON University of Bath Exchange Student

COURTNEY LOUISE WOOD Honours Student Cardiometabolic Disease Group

normal), in conjunction with Dr Sean Lal from Sydney Heart Bank (over 17,000 samples, one of the largest in the world). We run a dedicated DbCM clinic in our hospital in which we use cardiac MRI to carefully characterise key features of DbCM including extracellular volume, microvascular disease, and fibrosis. Combining this meticulous phenotyping with our latest-generation metabolomics platforms allows a heretofore-unseen mapping of cardiac substrate dysregulation and its relationship to DbCM pathology. We have access to important clinical cohorts: the CANVAS clinical trial; in collaboration with Prof Alex Brown, 1000 Indigenous Australian DbCM patients (an important “at risk” population), along with DbCM samples targeted type 2 diabetic therapy. We have RESEARCH HIGHLIGHTS from our cardiac heart bank. We also have identified signatures of hepatic insulin We recently characterised metabolic extensive tools to probe mechanism: a resistance and of skeletal muscle insulin perturbations in heart failure. Using C57Bl/6J hyperphagic model of obesity- resistance, which we will use to guide human heart failure tissue and donor induced insulin resistance and HFpEF-DbCM therapy using medications that target heart controls, we identified metabolic (confirmed by echocardiography), which either of these organs. We are now testing pathway perturbations common to heart we have established in our laboratory and whether our signatures of liver insulin failure of different aetiologies. This enables is an excellent model of human diabetic resistance predict response to treatment development of strategies to improve cardiomyopathy and HFpEF; latest- with metformin, the first agent in the cardiac function in heart failure. generation metabolomic, lipidomic, and type 2 diabetes treatment algorithm that We are also on the cusp of developing a proteomic platforms; ex vivo Langendorff targets the liver. new diagnostic tool that will enable precision perfusion and induced pluripotent stem cell- Impact of diet on liver fat and therapy in diabetes. The primary cause of cardiomyocyte (iPSC-CM) models in which insulin resistance type 2 diabetes is insulin resistance, and we will determine the fate of stable-isotope We recently discovered a new pathway this resistance is mainly driven by the liver, labelled glucose, ketone body, and fatty acid that links liver fat to type 2 diabetes and skeletal muscle, or fat. Currently, there substrates; and iPSC-CMs homozygous for independently predicted future diabetes is no way to tell which of these drivers common loss-of-function variants in fatty 12 years ahead of diagnosis. We have just is causing the insulin resistance in an acid metabolism. completed a 20-week murine model individual. Each diabetes treatment targets Dietary-microbiome-metabolic using four dietary interventions, insulin liver or muscle insulin resistance to varying interactions in cardiovascular disease and glucose tolerance tests, stable- degrees. As each individual case of diabetes We are studying the interaction of dietary isotope labelled glucose tracing, is different, the current standard is to use macronutrients with the microbiome, hyperinsulinaemic-euglycaemic clamps a trial-and-error approach to find the best gut, and plasma metabolome on cardiac and liver histology. Now we will use pharmaceutical combination for that person. phenotypic expression. Recently, we metabolomics and proteomics to carefully Our discovery has transformative potential discovered a profound effect of high dietary examine the development of metabolic i.e. being able to identify the source of insulin fibre (resistant starch) diets on microbial perturbation at select timepoints during resistance in each person will help target profile and the plasma redox system, development of disease. For the final treatment precisely. energetics, gut-derived vitamins, citric acid stage of this project, we will examine We recently determined that high-fibre cycle metabolites, and a potent effect on these parameters in mice with genetic diets have profound effects on circulating tryptophan metabolism that confers anti- modifications in the above pathway to metabolites, particularly those derived from inflammatory effects. We are investigating determine causal effects on liver fat the gut microbiome. A certain metabolite further a tryptophan derivative that is and metabolic parameters. class in particular was dramatically elevated produced exclusively in the gut and seems in plasma. We believe they confer many of to have important roles in inflammatory- the benefits of this diet, and can be leveraged driven diseases like atherosclerosis and further to alter inflammatory diseases insulin resistance. “We are on the cusp like atherosclerosis to significantly Novel therapeutic strategies in of developing a new improve outcomes. type 2 diabetes Working in partnership with the Garvan diagnostic tool that Institute, we apply our omic technology to will enable precision deeply-phenotyped cohorts of patients with liver and muscle insulin resistance to guide therapy in diabetes.” 24 2018 Heart Research Institute Annual Review

DR ANNA WATERHOUSE Group Leader PhD BSc (Hons 1)

RESEARCH TEAM

CATHERINE FIU Biomedical Engineering Honours Student SALLY GAO Cardiovascular Research Assistant

GEORGIA HEFFERNAN NZ Summer Student Medical Devices GRACE MACKIE Research Assistant Group MAIRI ROBERTSON NZ Summer Student

JASNEIL SINGH Biomedical Engineering Sydney OUR MISSION Medical School Summer Student The mission of the Cardiovascular Medical and understand the interplay of events at Devices Group is to understand the biointerface and manipulate this interplay THOMAS SULTANA interaction of medical devices with patients’ to improve medical device function as well Biomedical Engineering blood, proteins and cells, with a view to as create novel devices, diagnostics and Honours Student develop more sophisticated and compatible drug and non-drug-based avenues ISABELLE VAN VUUREN materials for medical devices. for therapies. Biomedical Engineering We focus on how medical devices – such Our goal is to develop materials that Student Intern as artificial hearts, stents and bypass reduce foreign reactions in the body, STEPHEN YAU machines – interact with the body. The team and to reduce the incidence of blood Biomedical Engineering applies cutting-edge bioengineering tools clot formation and biofouling. Honours Student to develop new methodologies to assess Cardiovascular Medical Devices Group

“Our goal is to develop materials that reduce foreign reactions in the body, and to reduce the incidence of blood clot formation and biofouling.”

OUR IMPACT drugs. Device failure mechanisms and RESEARCH HIGHLIGHTS Despite the widespread use of medical how different disease states contribute Molecular Nanorobotics for Health, a devices in cardiovascular medicine – to them can be investigated with the aim project co-led by Dr Anna Waterhouse, was including artificial hearts, vascular stents, of developing new treatments or chosen as one of Sydney Nano’s five Grand vascular grafts, heart valves, pacemakers, preventative therapies. Challenges in recognition of its potential catheters and cardiopulmonary bypass social, economic and scientific impact. Bioengineering smart materials circuits – many side effects, such as Dr Waterhouse’s Grand Challenge project, Medical device thrombosis and biofouling blood clots (thrombosis) and microbe with collaborator and co-lead Dr Shelley leading to sepsis cause significant morbidity adhesion (biofouling), are promoted by Wickham, will build molecular nano-robots, and mortality worldwide. Furthermore, the materials used to make these devices. self-assembled from biomolecules, which there is an urgent need to reduce the Thrombosis of medical devices is currently will be capable of travelling through the complications that arise from drugs managed with medication that can cause body to diagnose and treat early disease. designed to combat these issues, such as additional complications, such as bleeding This project will be the first molecular anticoagulants that cause bleeding and the from antiplatelet or anticoagulant drugs. nanorobotics platform for health and overuse of antibiotics that result in antibiotic Additionally, biofouling is treated with medicine in Australia. resistant pathogens. Using bioengineering antibiotics; however, antibiotics cannot strategies, increasingly sophisticated Dr Waterhouse was also the recipient of a always penetrate the biofilm and the overuse materials can be constructed. By combining 2018 Ramaciotti Health Investment Grant of antibiotics is leading to antibiotic-resistant physical, chemical and biological surface for the project Reducing blood clotting pathogens. Increased understanding of modification methods, medical devices can complications from cardiovascular medical biointerface interactions and methodology be manipulated to interact with, repel or devices. This work investigates coating to assess materials could lead to the adhere proteins or cells to improve medical devices such as bypass machines and development of new, more compatible device function, create novel diagnostics ventricular assist devices (to help a failing materials and devices to reduce the use of and medical devices, and both drug and heart pump blood) with a novel ‘non-stick’ drugs, improve diagnostics for early disease non-drug-based avenues for therapies. liquid interface. detection and reduce risks for patients.

RESEARCH PROJECTS Biointerfaces Understanding the interactions of medical devices with patients’ blood, proteins and cells will allow the development of more sophisticated and compatible materials for medical devices for the diagnosis and treatment of cardiovascular disease. To achieve these goals, we utilise cutting- edge bioengineering tools to develop new methodologies to assess and understand the interplay of events at the biointerface. This includes immobilising proteins or creating anti-adhesive coatings and investigating the biological response at the interface of the materials using advanced microscopy and surface analysis tools. Biomimetic model systems Advances in material fabrication techniques and 3D printing in micro and nanotechnology have revolutionised bioengineering, allowing high precision manipulation of materials for modelling medical systems and devices in the lab. Using these strategies, biomimetic in vitro model systems can be generated to recreate physiological conditions to evaluate medical device materials, geometries and 26 2018 Heart Research Institute Annual Review

Cell Therapeutics Group

ASSOCIATE PROFESSOR SANJAY PATEL Group Leader FCSANZ FRACP MBBS (Hons 1) PhD

RESEARCH TEAM OUR MISSION The mission of the Cell Therapeutics Group is to DR JENNIFER BARRACLOUGH reduce death and disability associated with heart and PhD Student lower limb arterial disease by reducing atherosclerotic DR KRISTEN BUBB plaque build-up. Visiting Scientist Our research aims to develop novel therapies to SIMRAN DAHIYA target atherosclerosis (arterial blockages) and its Visiting Student consequences (heart attack). Our treatment mission is to develop dedicated agents that specifically target the DR RAHUL KURUP inflammation that drives coronary plaque instability. PhD Student Our work is performed in collaboration with the Clinical JACK HYWOOD Research, Vascular Complications and Atherosclerosis PhD Student and Vascular Remodelling Groups within the HRI, drawing upon their expertise in each area of research. BRADLEY TUCKER Visiting Student Cell Therapeutics Group

“Our research identified the potential of colchicine in the treatment of ACS patients.”

OUR IMPACT Determining the anti-atherosclerotic properties One Australian dies from an acute coronary syndrome of TRAIL (ACS) every 51 minutes. Failure to specifically target Through collaboration with HRI’s Vascular Complications persistent coronary inflammation, which drives high Group, we continue to study potential therapies to boost rates of recurrent events, is likely a major factor. TRAIL, a novel mediator with marked anti-inflammatory To address this problem, our program’s overarching and anti-atherosclerotic properties, in patients with aim is to (1) elucidate new inflammatory pathways coronary disease. This work has resulted in several in ACS patients and (2) re-purpose established anti- presentations at international cardiovascular meetings, inflammatory drugs that target these pathways. and two publications. We have focussed on colchicine, a safe, cheap and effective anti-inflammatory agent. Our program RESEARCH HIGHLIGHTS was the first to show that colchicine has striking Our research identified the potential of colchicine in athero-protective effects. Our findings are recognised the treatment of ACS patients. The research program, internationally, with 20 papers and 25 presentations established in 2014, initially aimed to test the acute (at national and international scientific symposia) in effects of colchicine in the cardiac catheterisation lab. the last five years. Notably, this program’s work We developed a safer and more robust technique for has been cited 202 times by groups in 16 countries sampling blood from the coronary sinus in order to (Google Scholar), demonstrating its reach. We have measure trans-coronary cytokine gradients (Martinez et received significant national and international media al, IJC 2014). This provided the basis for ongoing studies. attention (Sydney Morning Herald, national evening In 2015, we showed that a single dose of oral colchicine news, TCTmd, heart.org). significantly reduces trans-coronary gradients of key inflammatory cytokines, all of which are highly predictive of future events in coronary artery disease patients RESEARCH PROJECTS (Martinez et al JAHA 2016). Determining the effects of colchicine on advanced atheroma/infarct size To address mechanism and strengthen research impact, This international collaborative study uses novel we described monocyte inflammasome activation in ACS murine models of atherosclerosis to understand patients and how colchicine attenuates this. (Robertson molecular athero-protective properties of colchicine. et al, Clin Sci 2016). We currently have two papers under review demonstrating inhibitory effects of colchicine Understanding the effects of colchicine on on chemokines and miRNA, relevant to inflammation chemokine expression and atherosclerosis. Using our technique of invasive blood sampling in the cardiac catheterisation laboratory, we study here the In 2017, we established a CT coronary angiography acute effects of colchicine on chemokines, key pro- program at RPAH, resulting in our third major colchicine inflammatory mediators, in ACS patients. The work publication, further strengthening our proposal resulted in one abstract presentation at the CSANZ that colchicine is athero-protective, through plaque annual meeting, which was the subject of the ISHR stabilisation, independent of statin use (Vaidya et al, student prize. JACC imaging 2017). As acute stroke and ACS share common pathophysiologic mechanisms, we recently Effects of colchicine on miRNA levels in coronary conducted a meta-analysis of the effects of colchicine disease patients on stroke incidence (accepted for publication in We continue to collaborate with A/Prof Hardiker's groups Clinical Therapeutics). Taken together, our work at the NHMRC Clinical Trial Centre to determine effects provides compelling mechanistic evidence for a of colchicine on miRNA signatures in ACS patients. therapeutic role of colchicine in acutely suppressing Effects of colchicine on metabolomic profiles in athero-inflammation, stabilising vulnerable plaque coronary disease patients and improving clinical outcomes. Via collaboration with HRI’s Cardiometabolic Disease Group, we continue to investigate new mechanisms of action of colchicine in ACS patients. This work has resulted thus far in one presentation at the CSANZ annual meeting. 28 2018 Heart Research Institute Annual Review

Clinical Research Group

PROFESSOR DAVID OUR MISSION CELERMAJER AO The primary mission of the Clinical Research Group is to detect cardiac and Group Leader vascular disease promptly in order for PhD MBBS MSc (Oxon) DSc FAHA FRACP FAA treatments to be administered at an early, optimal stage to prevent serious late consequences of disease. RESEARCH TEAM Our goals are to detect and prevent DR CLARE ARNOTT complications from three primary types Visiting Scientist of serious heart disease: DR JULIAN AYER 1. Atherosclerosis – the narrowing of the Visiting Scientist main blood vessels in the body, and the VIVIAN KIENZLE main cause of heart attack and stroke. Senior Research Assistant 2. Pulmonary vascular disease – the DR GONZALO MARTINEZ narrowing of the main blood vessels Visiting Scientist to the lungs, which can lead to overload of the right side of the heart. CALUM NICHOLSON 3. Congenital heart disease – as an Research Assistant increasing number of adults surviving with inborn heart problems still require extensive care and treatment. Clinical Research Group

“We aim to detect heart and blood vessel abnormalities at an early stage before the condition becomes irreversible.”

OUR IMPACT Early detection and prevention of advanced heart disease may save hundreds of thousands of lives each year. We aim to detect heart and blood vessel particularly beneficial in dampening down Adult Congenital Heart Disease Clinics in abnormalities at an early stage before the the inflammation associated with acute the country, addressing medical issues such condition becomes irreversible. We design heart attack, with potential benefits for as this. Our work with these young adults interventions to treat a wide range of patients in this situation. Dr Gonzalo has focused on rarely studied conditions abnormalities, with a particular focus on Martinez, a cardiologist from Chile, helped such as Ebstein’s anomaly of the heart, the prevention of atherosclerosis in children perform this work, collaborating with our congenitally corrected transposition of the and young adults who have risk factors Group for 18 months. great arteries and dextrocardia (the unusual for early heart disease, obesity, exposure situation where the heart lies on the right to passive smoke in the home, those who Early detection of pulmonary side of the chest rather than the left). We smoke themselves, or those with high levels vascular disease have also collaborated with the Department of cholesterol. We also concentrate on all Pulmonary vascular disease, or high blood of Radiology at RPAH to make important subject ages with pre-diabetes or diabetes, pressure in the lungs, is a very severe discoveries about a condition called non- and babies who are born small at full term. condition affecting young adult Australians compaction of the heart, where the heart and (as we are increasingly finding out) older is not assembled efficiently, resulting in Australians also. We conducted two projects ‘spongy’ rather than well-compacted muscle. RESEARCH PROJECTS to outline novel techniques for detecting We have discovered a new diagnostic tool to We have a series of projects to detect early this complication before it caused more detect this, using MRI of the heart, and have blood vessel damage in children and young serious health problems. The first technique also defined its prevalence in young adults adults as well as programs to intervene to was based on ultrasound of the heart and with congenital heart disease, as well as its prevent late serious complications. We examined the right ventricle, while in the functional consequences. also study heart disease in those with other, researchers placed a thin catheter congenital cardiac abnormalities with a in the main blood vessels to the lungs view to minimising complications and and studied the pattern of blood flow and RESEARCH HIGHLIGHTS maximising quality of life. pressure using sophisticated mathematical In a paper in the Journal of Pediatrics, models. Papers describing this research were Detecting heart attacks we have shown that the trajectory of weight published in major international journals. In collaboration with Associate Professor gain in obese children is very important Sanjay Patel and his Group at HRI, we Young adults with congenital in determining outcomes in teenage life, have discovered that the heart releases heart disease influencing body fat and cholesterol levels. certain proteins and cell remnants during There are now more young adults than A pattern of early weight gain in the first two a disruption of plaques (during heart children with congenital heart disease years of life is much more maladaptive than attacks) and we can now detect these in (inborn heart abnormalities), with the a similar weight gain between the ages of the laboratory. We also have preliminary population continuing to grow in number two to five years. data indicating that a well-known anti- and complexity. At the Royal Prince Alfred inflammatory drug, colchicine, may be Hospital (RPAH), we run one of the largest 30 2018 Heart Research Institute Annual Review

DR FREDA PASSAM Haematology Group Leader MD PhD FRACP FRCPA

Research Group RESEARCH TEAM DARRYL CHIU USYD Summer Student

ALEXANDER DUPUY Research Assistant

DR ANGELINA LAY Postdoctoral Fellow, Centenary Institute

ELISABETH REUBERGER Visiting Student of Biomedical Sciences, University of Vienna, Austria Haematology Research Group

OUR MISSION RESEARCH PROJECTS RESEARCH HIGHLIGHTS The mission of the Haematology Research Thiol isomerases as novel A recent highlight of our research Group is to discover new mechanisms antithrombotic targets program has been our finding of a novel of clot formation which can lead to We have identified a novel clotting pathway partnership between force and disulphide the development of efficient and safer that involves enzymes, named thiol bond reactions that controls the association antithrombotic drugs. isomerases. Inhibitors of these enzymes of the platelet receptor a2bb3 to its ligand, can be developed into drugs that treat fibrinogen. Binding of the platelet receptor We have a special interest in the thrombotic disease. a2bb3 to fibrinogen causes pathological development of biochips for the detection blood clotting – the precipitating event and monitoring of thrombotic tendency. Redox biomarkers in thrombotic disease in heart attack and stroke. Therapeutic We are focused on the role of enzymes, An imbalance of oxidants/antioxidants blockade of this receptor in humans can named thiol isomerases, in the development in our blood (redox imbalance) causes cause life-threatening bleeding, which of thrombosis and their potential as novel alterations to blood proteins that can lead to has restricted the clinical use of this antithrombotic targets. In the clinical space, thrombosis. We have found redox-modified intervention. Our studies point to how this we are interested in the management of proteins in the blood that are associated integrin may be targeted in a less aggressive venous thrombosis in the community and with thrombosis. These redox biomarkers way. Triggering release of fibrinogen from high-risk thrombosis. can be used to identify patients that will the platelet receptor by agents that react benefit most from drugs that restore a with the target disulfide bonds is predicted healthy redox balance. OUR IMPACT to limit the growth of a thrombus rather Biochips for the assessment of Current anti-thrombotic treatment is not than blocking it completely. We have haemostasis and thrombosis effective or has bleeding side effects e.g. one established the Mechano-Redox Research Many patients with bleeding and clotting in six patients who have had a heart attack node in collaboration with the Centenary disorders go undetected by routine will have another attack despite optimal Institute to further study this mechanism, laboratory tests because these do not reflect treatment. We aim to discover targets for which is a first-of-its-kind in Australia for the the conditions in our circulation. Our Group new and safe anti-thrombotics, and find broader biomedical research community. uses biochips in a microfluidic system that answers to fundamental biological problems simulates human circulation. These biochips that will enable the development of new can be used to detect a thrombotic or diagnostics and treatments for patients with bleeding tendency in patient samples. blood clots. New diagnostics are important because routine tests are not able to detect a thrombotic tendency in half the cases.

“We aim to uncover new mechanisms leading to thrombosis that will enable the development of new diagnostics and treatments for patients with blood clots.” 32 2018 Heart Research Institute Annual Review

Heart Rhythm and Stroke Prevention Group

PROFESSOR BEN RESEARCH TEAM

FREEDMAN OAM JIALIN LI Group Leader MPhil Student and Research Assistant FACC FAHA FCSANZ FESC FRACP MBBS PhD DR NICOLE LOWRES Postdoctoral Research Fellow

JESSICA ORCHARD Research Coordinator and PhD Student Heart Rhythm and Stroke Prevention Group

OUR MISSION RESEARCH PROJECTS The mission of the Heart Rhythm and Stroke Prevention • Atrial Fibrillation Screening, Management, and Group is to prevent strokes caused by silent atrial guideline-Recommended Therapy (AF-SMART) fibrillation (AF) by screening for AF in various settings, studies: in metropolitan and rural general practice and to treat it using electronic decision support tools using smartphone ECG and a suite of eHealth tools to increase effective preventive treatment. • Patient self-screening for AF in general practice Our research relates to clinical implementation, with a using screening stations (to commence 2019) focus on finding novel ways to implement strategies to • Patient self-screening using a smartphone ECG to reduce stroke by detecting unknown silent AF. AF is the identify recurrence of postoperative AF after non- most common abnormal heart rhythm – it is estimated cardiac surgery and medical admissions: in Concord that individuals over the age of 40 have a one in four Hospital, Royal Perth Hospital, and Gosford Hospital lifetime risk of developing AF. AF is responsible for one third of all strokes, which are largely preventable by • Collaboration with the Poche Centre to screen for anticoagulant medications that stop clots from forming AF in Indigenous Australians in remote and rural inside the heart. Unfortunately, AF is frequently silent, NSW, NT and WA especially in older people who are at greater risk of • Collaboration with researchers in Royal Melbourne stroke, with the first sign of AF being a severe stroke. Hospital to detect AF post-stroke in Australia, Our AF screening research extends through Hong Kong and China (SPOT-AF) collaborations with primary care and specialist clinics • Collaboration with researchers at the Chinese in Australia, the USA, Shanghai, Hong Kong, Japan, University of Hong Kong to screen for AF in cardiac Vietnam, Germany and the UK. clinics, general practice and the community Another major interest of our Group is to determine (over 20,000 people screened to date) whether our indigenous population has a higher burden • Collaboration with researchers in Shanghai to screen of AF by screening in remote and rural Australia, in for AF in community centres (AF-CATCH) (ongoing) collaboration with the Poche Centre and the University • Collaboration with Hamburg and Gutenberg Heart of Auckland, NZ. studies (Germany) on screening for AF (ongoing) • Collaboration with researchers in Frankfurt Germany OUR IMPACT about epidemiology of AF (ongoing) Our main activities are to determine how best to • Collaboration with researchers in Oklahoma (USA) screen for AF at scale, and to prevent as many strokes to screen for AF in tribal Indian Clinics (ongoing) as possible. The more people screened and treated, the more strokes we can prevent. • Collaboration with researchers in Toyama (Japan) to investigate the incremental yield of annual We continue global advocacy for screening for AF screening (ongoing) through the AF-SCREEN International Collaboration. This is likely to change guidelines and influence future government policy and have a global impact on stroke RESEARCH HIGHLIGHTS reduction. In fact, the Australian Heart Foundation and The Heart Rhythm and Stroke Prevention team were Cardiac Society of Australia and New Zealand 2018 invited to give featured presentations at the European guideline on the management of AF had opportunistic Society of Cardiology on eHealth research about screening for unknown AF as its first recommendation, screening for AF. The meeting was extremely well with a practice point being about use of a handheld attended with 30,000 attendees, and as its theme ECG pioneered by our Group, quoting our Group’s was eHealth, was a particularly important inclusion. work in its recommendation. This coincided this year with the team’s publication in Journal of the American Heart Association of our work on use of a suite of eHealth tools. “Our research relates to clinical implementation, with a focus on finding novel ways to implement strategies to reduce stroke by detecting unknown silent AF.” 34 2018 Heart Research Institute Annual Review

High Blood Pressure Group

OUR MISSION The High Blood Pressure Group aims to determine how the central “The focus of our research is to tease nervous system manages long-term control of blood pressure, apart the mechanisms responsible and how the brain copes when such systems malfunction. Most recently, focused research has begun to address the role of for excessive sympathoexcitation that inflammatory and ischaemic systems in the brain in relationship results in cardiovascular disease.” to blood pressure control. Our research addresses all aspects of the brain’s control of blood flow to different areas of the circulatory system. the brain chemical pituitary adenylate cyclase activating polypeptide (PACAP), and the activity of microglia – the immune cells of the brain, which express receptors for nearly every brain OUR IMPACT chemical known. Blood pressure plays a vital role in the proper functioning of the heart and circulation, and constantly changes in response Specific studies focus on: to the activity requirements of the body. High blood pressure • Investigating the role of PACAP in models of sleep apnoea (hypertension) is a major cause of cardiovascular disease and • Investigating the role of the endogenous opioid system in the occurs in progressive disorders such as sleep apnoea and epilepsy. hyperglycemia associated autonomic failure (HAAF) If left untreated, worsening hypertension can lead to kidney • Understanding the autonomic consequences of seizure (NHMRC failure, heart attack or stroke. The High Blood Pressure Group’s funded project in collaboration with Melbourne University) work is aimed at learning how hypertension is caused in order to develop new preventative measures. • Investigating the role of microglia in cardiovascular control.

RESEARCH PROJECTS RESEARCH HIGHLIGHTS Hypertension is almost always preceded by increased excitatory Our research into the cardiovascular consequences of sleep apnoea nerve signals from the brain. Increased sympathoexcitation leads continues, and we have discovered important mechanisms into how to hypertension because persistent activation of the sympathetic the brain detects, processes, and responds to repeated episodes nervous system – especially when intermittent – causes a vicious of hypoxia. This work resulted in several publications in 2018, has spiral of narrowing of arteries, hypertension, organ damage and been the subject of numerous conference presentations, and has further increases in sympathoexcitation. formed the basis for expanding our research direction into the area of glucose regulation. We have discovered that the u-opioid receptor The focus of our research is to tease apart the mechanisms is responsible for the dangerous situation that can occur in type 1 responsible for excessive sympathoexcitation that results in diabetics, where, after repeated episodes of low blood glucose, the cardiovascular disease. Our most recent findings have implicated body’s ability to detect low blood glucose is lost, putting the person two factors in the dangerous elevation of blood pressure: at risk of seizure and death. High Blood Pressure Group

PROFESSOR PAUL PILOWSKY RESEARCH TEAM Group Leader DR MELISSA FARNHAM PhD BMedSc (Hons) BMBS FAHA Unit Leader

MYFANWY COHEN PhD Student

ZOHRA KAKALL PhD Student

SEUNG JAE KIM PhD Student

DR POLINA NEDOBOY Postdoctoral Scientist 36 2018 Heart Research Institute Annual Review

Thrombosis Group

RESEARCH TEAM PROFESSOR SHAUN JACKSON IMALA ALWIS Senior Research Scientist Group Leader MBBS (Hons) BMedSci (Hons) PhD BRIANNA COULTER Research Assistant

DR ROXANE DARBOUSSET Postdoctoral Scientist

DR MARC ELLIS PhD Student

DR LINING (ARNOLD) JU Postdoctoral Scientist OUR MISSION are typically more resistant to the benefits The mission of the Thrombosis Group is to of “classical” antithrombotic therapy. The DR SABINE KOSSMAN establish a new and innovative approach comprehensive research approach adopted Postdoctoral Scientist to the prevention and treatment of heart by the Thrombosis Group is designed to ASHLEY LEE disease and stroke, positioning Australia as identify and target thrombosis risk in Research Assistant a leader in the discovery and development such diseases. of innovative therapies for the treatment JESSICA MACLEAN of atherothrombotic diseases. PhD Student RESEARCH PROJECTS Our research is focused on determining “Bad Blood”: unravelling the link between DR SOPHIE MAIOCCHI the mechanisms underlying clot formation oxidative stress, dying platelets and Postdoctoral Scientist in healthy individuals, and applying this pathological blood clotting knowledge to better understand the EMILY MCCARTHY Oxidative stress is essentially an imbalance mechanisms leading to platelet hyperactivity NZ Summer Student between the production of free radicals and pathological blood clot formation to and the ability of the body to counteract DR LAURA NORTON ultimately develop safer and more effective or detoxify their harmful effects through Postdoctoral Scientist therapies to treat cardiovascular diseases, neutralisation by antioxidants. including heart attack, stroke, diabetes and ASSOCIATE PROFESSOR the metabolic syndrome. Oxidative stress regulates a wide range SIMONE SCHOENWAELDER of cellular functions, including cell Senior Principal Research Fellow proliferation, metabolism, gene transcription DR QIAN (PETER) SU OUR IMPACT and cell death. Oxidative stress primarily Atherothrombosis is arguably Australia’s induces death by activating cell death Visiting Postdoctoral Scientist greatest healthcare problem, affecting over (apoptotic) pathways in nucleated cells. LUCY THAWLEY 50% of the adult population. Despite intense The mechanisms by which oxidative stress Research Assistant investigation over the last 40 years into the regulates the death of anucleate cells, such discovery and development of more effective as platelets, remains ill-defined, as does its DR AMELIA TOMKINS antithrombotic drugs, the impact of these relevance to atherothrombosis in vivo. Postdoctoral Scientist therapies on mortality rates has remained We have identified a new mechanism of disappointingly low. This situation is likely DR MIKE WU pathological blood clotting (thrombosis) to worsen in the future due to the rapidly Postdoctoral Scientist and vascular occlusion that is triggered growing incidence of obesity, diabetes and by dying platelets, leading to platelet- DR YUPING YUAN the metabolic syndrome – diseases that Senior Research Fellow neutrophil macroaggregates, and vascular Heart Rhythm and StrokeThrombosis Prevention Group

occlusion of the microvasculature. Our side effects, limiting its widespread use. with fewer bleeding complications. recent studies suggest a major role for We are working on several novel approaches This research lays the foundation for oxidative stress in inducing platelet death in to improve upon existing stroke therapies, the development of safe anticoagulants ischemic organs in vivo. Our current studies making them safer and more effective. for the treatment of thromboembolic aim to gain a greater understanding of this While it is broadly accepted that restoration diseases such as stroke in the future. novel thrombotic mechanism, in order to of blood flow to the brain will limit the develop novel therapeutic treatment(s) to progression of cell death and improve patient reduce formation of platelet-neutrophil outcome after stroke, there is evolving RESEARCH HIGHLIGHTS macroaggregates and remote organ evidence that reopening the blocked artery We have uncovered why common blood injury and death. (recanalization) does not always lead to thinners used to protect millions worldwide reperfusion of the small vessels of the brain. from life-threatening blood clots don’t Solving a sticky clotting problem Failure of cerebral reperfusion correlates work as well for people with diabetes. in diabetes with worse prognosis for stroke patients. Our The study, published in the journal Nature The leading cause of death in diabetes is ongoing studies have successfully developed Communications, is the first to show the cardiovascular disease, with up to 70% of a novel mouse model of thrombolysis (iCAT) mechanism that triggers catastrophic deaths relating to the development of blood that for the first time allows us the ability clotting in these at-risk patients. clots supplying the heart (heart attack) or to examine the efficacy of novel drugs to This discovery provides scientists with a brain (ischemic stroke). Diabetic individuals facilitate clot lysis (recanalization), restore potential new way to protect the growing are more prone to develop blood clots, and perfusion in the brain, as well as determine number of diabetics from suffering from these clots are more resistant to standard whether cerebral damage and cognitive heart attack and stroke. anticlotting therapies. impairment associated with stroke Described as the epidemic of the 21st We have discovered a new biomechanical are reduced. century, diabetes represents the biggest clotting mechanism severely affected by We are using this model to assess the challenge confronting the Australian health diabetes that is resistant to the beneficial efficacy of currently approved and novel anti- system. Cardiovascular disease kills 70% of effects of commonly used antithrombotic clotting agents to facilitate stroke treatment. people with diabetes, and with now over 1.2 agents (see p15). million people with diabetes in Australia, it COLLABORATIVE PROJECTS Studies in the laboratory are also examining is a huge – and growing – problem. While Developing safer anti-clotting agents the role chronic oxidative stress plays in people with diabetes are at increased risk derived from “Mother nature” amplifying blood clotting in diabetes, and of heart disease and stroke, they do not The powerful enzyme thrombin is by far the the mechanisms by which oxidative stress respond as well to blood thinning drugs most robust activator of platelets and blood may modify platelet receptors to enhance like aspirin and Plavix that are used clotting (coagulation) in both physiological adhesion. These studies may identify novel haemostasis and pathological thrombotic to prevent these conditions. targets with which to treat thrombosis response. Therapeutic inhibition of thrombin associated with diabetes. To investigate this drug resistance, our has been shown to be an effective anti- team studied the blood of people with type Developing novel approaches to the thrombotic agent, however, all current one diabetes as well as lab models of the treatment of ischaemic stroke inhibitors of this enzyme lead to severe disease, and unexpectedly discovered a The development of a blood clot in the bleeding complications. new pathway responsible for triggering cerebral circulation (ischaemic stroke) is In studies performed in collaboration the formation of blood clots. We found the third most common cause of death and with Professor Richard Payne, ARC Future that when blood flow is disturbed, the the most common cause of adult disability Fellow at The University of Sydney’s School mechanical compression forces that are globally. The central goal of stroke therapy of Chemistry, we have characterised novel generated within the disturbed blood flow is the prompt reperfusion of occluded blood anticlotting agents that have been based can activate blood clotting cells, leading vessels to minimise tissue death. around naturally occurring proteins found to growth of bigger clots. We believe this The delivery of fibrinolytic agents modelled in saliva of mosquitos. process occurs in all people, but the blood on tissue-type plasminogen activator cells of patients with diabetes appear to Our studies have demonstrated that these (t-PA) is the only clinically approved means be more sensitive to these mechanical bug-derived proteins are able to dissolve available to stroke patients. Despite this, forces, triggering larger blood clots. blood clots in a disease model of thrombosis the use of t-PA is associated with significant We are developing a drug targeting an enzyme called Class I PI 3-kinase, which has been found to target this new pathway of blood clotting and appears to be effective in preventing disease-forming clots in diabetic patients. The drug has already proven successful in phase 1 human trials. Further testing to understand this mechanism in people with diabetes is underway, and we are hopeful that it could be used to identify which patients are most at risk of clotting problems. 38 2018 Heart Research Institute Annual Review

DR MARY KAVURMA Group Leader BSc (Hons) PhD

Vascular RESEARCH TEAM LAUREN BOCCANFUSO Honours Student Complications DR SIÂN CARTLAND Senior Postdoctoral Scientist Group PRADEEP CHOLAN PhD Student

SCOTT GENNER Research Assistant

MANISHA PATIL Honours Student

DHANYA RAVINDRAN PhD Student

HANNAH VAN DER WOUDE NZ Summer Student Vascular Complications Group

OUR MISSION RESEARCH PROJECTS “Our work will help The mission of the Vascular Complications Our research themes for 2018 focused on: Group is to understand the pathogenesis uncover new strategies • Mechanisms that reduce oxidative of blood vessel disease, and using this stress in vascular cells in disease and therapeutics knowledge, identify new strategies to improve function and reduce the burden • How white blood cell functions protect to combat disease, of cardiovascular disease (CVD) in people. against atherosclerosis ultimately improving Our research uses various models, • The effect of chemokine inhibition quality of life and genetic manipulation, and biochemical on angiogenesis and molecular biology tools to dissect • Examining vascular cell-specific effects life expectancy.” how blood vessels become dysregulated, on blood vessel structure and function, with an emphasis on changes to gene and in angiogenesis expression, vascular cell adaptation and atherosclerosis by maintaining endothelial • Identifying new mechanisms that function in both normal and abnormal cell homeostasis. Specifically, we found regulate vascular calcification in the settings in the blood vessel wall. that TRAIL has a negative correlation with blood vessel wall. plasma oxidative stress in CVD patients, suggesting that its presence is protective. OUR IMPACT Furthermore, we showed that mice lacking RESEARCH HIGHLIGHTS Our research aims to understand the TRAIL had increased CVD, oxidative stress The Vascular Complications Group molecular, biochemical and cellular and impaired endothelium. In an in vitro published a significant achievement in mechanisms underlying blood vessel model of oxidative stress, we showed that Free Radical Biology Medicine. diseases, focusing on atherosclerosis TRAIL treatment reduced oxidative stress, and its complications, including peripheral In CVD, the first point of damage occurs at and maintained endothelial cell integrity by vascular disease and diabetes. By providing the endothelial cell layer or the innermost acting on multiple molecules important in new knowledge as to how blood vessels layer of a blood vessel, which is in direct maintaining cell homeostasis. Understanding become dysregulated in CVD and related contact with the blood. Oxidative stress, the role TRAIL plays in normal physiology pathologies, our work will help uncover elevated in CVD, can damage this cell layer. and disease may lead to potential new new strategies and therapeutics to We found that TNF-related apoptosis- therapies to improve endothelial function combat disease, ultimately improving inducing ligand (TRAIL) protects against and atherosclerosis. quality of life and life expectancy. 40 2018 Heart Research Institute Annual Review

RESEARCH TEAM

PROFESSOR ANGELA MAKRIS Co-Lead, Visiting Scientist

DR SHIKHA AGGARWAL PhD Student

DR KATRINA CHAU PhD Student

KEZIA EYRE Medical & Honours Student

DR SUZANNE PEARS PhD Student

DR RENUKA SHANMUGALINGAM PhD Student

ELINA THADHANI USA, International Winter Student

DR MIKALA WELSH MRES Student

DR BEI XU Senior Research Assistant

PROFESSOR ANNEMARIE Vascular HENNESSY AM Group Leader Immunology MBBS PhD FRACP MBA Group Vascular Immunology Group

“Our work is directly translatable to women in pregnancy, resulting in an immediate impact through translational research efforts.”

projects of the Group. The placenta and RESEARCH PROJECTS women’s health research adds important The role of placenta antibodies in causing and novel dimensions to the overall blood vessel damage and hypertension research plan at HRI. A study of 351 women enrolled in a past preeclampsia study, this work also involves Our work is strongly driven by a women’s growing placentas in the laboratory and action group, The PEARLS Group, who looking at the impact of specific antibodies provide community engagement and review on placental growth. of research plans, as well as funding to support the Vascular Immunology Group’s The potential for placental growth to work. In 2018, The PEARLS Group raised prevent and reverse preeclampsia over $100,000 for the Vascular Immunology Placental growth factor is a recently Group for a PhD Scholarship and to support discovered protein originating in the placenta, our Early Career Researchers to focus which is responsible for blood supply and on improving outcomes for women with oxygen to the placenta and baby. preeclampsia and to understand its causes. Safer prolongation of pregnancy A study of placenta growth and treatments that provide for a safer prolongation of OUR MISSION OUR IMPACT pregnancy without premature delivery. It is the mission of the Vascular Our research goals are to better understand Immunology Group to better understand the causes of preeclampsia. By measuring The pharmacology of aspirin in the causes of preeclampsia (high blood the functions of the placenta and predicting preeclampsia pressure in pregnancy), the condition’s preeclampsia, we seek to provide new, safe Aspirin as a useful drug to prevent impact on women during pregnancy, and treatment which would allow the pregnancy preeclampsia is being examined in terms the impact on long-term cardiovascular to progress to full term, thus reducing the of patient acceptability, drug dosing and its health. We seek to develop new drug burden of premature delivery and also, long- effect in preeclampsia prevention in a wide treatments for preeclampsia. term, the risk to women's heart health. population across Sydney and south western Sydney. Our research focuses on how placentas work Our work is directly translatable to women and the benefits of placental treatment to in pregnancy, resulting in an immediate Novel drug treatment for early severe women that we look after in clinical practice. impact through translational research preeclampsia Professors Hennessy and Makris, and Drs efforts. Our Group has a strong international In partnership with major researchers Aggarwal, Chau and Shanmugalingam and national reputation for the quality and in the USA and Sweden, the Group is are active physicians caring for hundreds effect of our research plans. If preeclampsia investigating the effect and safety of of women annually with preeclampsia, could be prevented, then one of the new treatments targeting the placenta, hypertension, vascular and kidney diseases. strongest risk factors for women’s heart for use in early severe preeclampsia. Our research scientists, Drs Xu, Pears and disease could also be prevented or reduced. Welsh are experts in animal studies and in This is an important long-term goal for growing placentas, and thus support the women’s heart health. 42 2018 Heart Research Institute Annual Review

Inflammation and Fibrosis Research

RESEARCH TEAM

DR BENJAMIN RAYNER Senior Research Officer

LEILA REYES PhD Student

VICKIE TANG PhD Student

SALLY VUONG Research Assistant

YUNJIA (CARMEN) ZHANG PhD Student Inflammation and Fibrosis Research

“Cardiovascular morbidity is a major ongoing economic and social burden in developed countries, with prevalence rates of heart failure of up to 2% within the Australian population.”

In addition to the research conducted by its 13 groups, RESEARCH PROJECTS HRI also conducts research into inflammation and fibrosis. Industry Partnership (Pharmaxis Pty Ltd): Investigating the The aim of this work is to better delineate the contributing efficacy of lysyl oxidase like 2, monoamine oxidase and MPO factors involved in cardiovascular disease development by inhibitors in myocardial ischemia reperfusion (I/R) injury understanding the underlying cellular and tissue mechanisms This project involves the use of an in vivo open-chest rat model that drive the disease. of myocardial ischaemia and I/R injury to ascertain the protective The research focuses on a range of causative aspects of effect of novel compounds on heart remodelling characteristics cardiovascular disease, from the role that the balance between following heart attack. oxidative stress and antioxidant defense systems play within cells The effect of SeMet supplementation within cardiovascular of the vasculature and heart, to how to better combat atherosclerotic disease (CVD) lesion development through antioxidant therapy, through to development of better targeted therapy for heart attack patients. This PhD project involves the use of a murine model of atherosclerosis and concurrent in vitro studies in isolated Whilst improvements in intensive care have reduced the number human neutrophils and macrophages to investigate the cellular of deaths attributable to heart attacks, the damage caused by an mechanisms involved in extracellular trap formation and its role ischaemic event within the heart remains poorly managed, resulting in lesion formation. This project follows on from another PhD in ongoing morbidity. As a part of the body’s inflammatory repertoire, thesis on the effects of SeMet supplementation within the invading immune cells at sites of tissue damage following heart setting of I/R injury. attack release the enzyme myeloperoxidase (MPO), which results in the continual and specific production of MPO-derived oxidants, further contributing to heart muscle remodelling, promoting tissue COLLABORATIONS injury and disease progression. Longer term, a heart attack causes • Dr Justyna Fert-Bober, Cedars-Sinai Medical Center, Los Angeles scar formation in the heart muscle, which leads to loss of muscular – Investigation into the role of peptidylarginine deiminase (PAD) power, affecting the ability of the heart to pump blood, resulting in isoforms in the promotion of cardiac fibrosis complete heart failure in extreme cases. Scar tissue is composed • Professor Clare Hawkins, University of Copenhagen, Denmark of the protein collagen, which is cross-linked to form a pronounced – Investigation into the molecular mechanisms of alignment in a single direction, resulting in inferior functional quality myeloperoxidase (MPO)-derived reactive-oxidant to the affected tissue. species-mediated damage and dysfunction within Through a CSIRO fellowship, Dr Benjamin Rayner has partnered the setting of atherosclerosis with an Australian pharmaceutical company, Pharmaxis Pty Ltd, who – The role of the unfolded protein response (UPR) in have developed a range of inhibitors targeting the specific processes, oxidative stress induced astrocyte dysfunction including those played by MPO and impaired collagen deposition, that • Associate Professor Paul Witting, The University of Sydney contribute to the scar formation and loss of heart function following – Assessing the efficacy of the nitroxide 4-MetT on inflammation heart attack. The partnership between HRI, CSIRO and Pharmaxis is and tissue damage within the setting of cardiac I/R injury aimed at testing the efficacy of these inhibitors at reducing oxidative – Assessing the efficacy of therapeutic thiocyanate stress/damage and/or alleviating the heart tissue scar formation supplementation within the setting of inflammatory following heart attack, thus providing greater beneficial therapeutic bowel disease (IBD) outcomes for patients suffering the disease. • Dr Lana McClements, University of Technology Sydney – Assessing the role of FK506-binding protein like (FKBPL) in cardiac I/R injury RESEARCH IMPACT • Dr Tharani Sabaretnam, Centre for Motor Neuron Disease Cardiovascular morbidity is a major ongoing economic and social Research, Macquarie University; Dr Tharusha Jayasena burden in developed countries, with prevalence rates of heart failure & Ms Sonia Bustamante, Centre for Healthy Brain Ageing, of up to 2% within the Australian population. Remodelling of heart University of NSW tissue following a heart attack involves detrimental scar formation, – Identifying analytical markers of disease within the brain leading to reduced heart function and progression to heart failure. • Associate Professor Ravinay Bhindi, Kolling Institute of Medical By targeting the underlying contributing mechanisms involved in Research, The University of Sydney these processes, our inflammation and fibrosis research seeks to – The role of the transcription factor early growth response-1 improve therapies and lead to better patient outcomes. (Egr-1) in tissue damage following I/R injury

44 2018 Heart Research Institute Annual Review

PhD Students

DR SHIKHA AGGARWAL SEUNG JAE KIM DR MIGUEL SANTOS Vascular Immunology Group High Blood Pressure Group Applied Materials Group ALEX CHAN DR RAHUL KURUP DR RENUKA SHANMUGALINGAM Applied Materials Group Cell Therapeutics Group Vascular Immunology Group DR KATRINA CHAU BOB LEE DR KELLY STANTON Vascular Immunology Group Applied Materials Group Clinical Research Group PRADEEP CHOLAN JESSICA MACLEAN DR RICHARD TAN Vascular Complications Group Thrombosis Group Applied Materials Group ZOE CLAYTON PRAVEESUDA (JOY) MICHAEL VICKIE TANG Cell Therapeutics Group Applied Materials Group Inflammation Group MYFANWY COHEN JESSICA ORCHARD ERIC YANG High Blood Pressure Group Heart Rhythm and Stroke Prevention Group Applied Materials Group DR MARC ELLIS DR SUZANNE PEARS YUNJIA (CARMEN) ZHANG Thrombosis Group Vascular Immunology Group Inflammation Group ELYSSE FILIPE DHANYA RAVINDRAN Applied Materials Group Vascular Complications Group ZOHRA KAKALL LEILA REYES High Blood Pressure Group Inflammation Group PhD Students | Select Prizes and Awards

Select Prizes and Awards

IMALA ALWIS DR LINING (ARNOLD) JU Thrombosis Group Thrombosis Group 2018 LMA/Optiscan Award for Best Best Publication Award – Heart Movie – International Microscopy Research Institute Congress (IMC19) Achievement and Career Development Award – Joint Annual Scientific Meeting MYFANWY COHEN of AAS/AVBS/HBPRCA High Blood Pressure Group Effective Data Presentation at SEUNG JAE KIM Conferences Workshop, HDR+ High Blood Pressure Group Student Grant – USYD International Graduate Student Award – Therapeutic Intermittent Hypoxia Retreat DR ROXANE DARBOUSSET Postgraduate Research Support Scheme – DR RICHARD TAN Thrombosis Group USYD Applied Materials Group Rising Star Award – Cardiovascular Symposium BOB LEE Student Research Publication Applied Materials Group Commendation Award – USYD CPC EMCR Seed Fund (Targeting platelet death, a novel approach to reduce EMCR Poster Award – Cardiovascular Rising Star Award – Cardiovascular ischaemia/reperfusion injury) – USYD Symposium, Cardiovascular Initiative Symposium, Cardiovascular Initiative Oral Presentation Award, Society PROFESSOR SHAUN JACKSON DR NICOLE LOWRES Student and Young Investigator Section Thrombosis Group Heart Rhythm and Stroke Prevention Group – World Congress of Tissue Engineering Ministerial Award for Cardiovascular Preventative and Clinical Cardiology Prize and Regenerative Medicine International Research Excellence – NSW session winner – Cardiac Society Australia Student Researcher Award, Heart Cardiovascular Research Network and New Zealand Research Institute

Carer’s Travel Scholarship to the ESC Young Investigator Award, Sydney ZOHRA KAKALL Congress – NSW Cardiovascular Cardiovascular Drug Discovery – High Blood Pressure Group Research Network Cardiovascular Initiative Postgraduate Research Support Scheme – USYD DR POLINA NEDOBOY VICKIE TANG High Blood Pressure Group Travel Grant – Federation of Inflammation Group European Neuroscience Societies Transnetyx Innovation Award, The Society for Free Radical Research Travel International Rising Innovator Class of Award to present at the 19th Biennial Meeting DR YEN CHIN KOAY 2018 – USYD of the Society-for-Free-Radical-Research- Cardiometabolic Disease Group International (SFRRI), Lisbon, Portugal DHANYA RAVINDRAN Young Investigators Award for Vascular Complications Group Best Poster, CVI Precision Medicine DR ANNA WATERHOUSE – Cardiovascular Initiative Best Student Mini-Oral Presentation – Cardiovascular Medical Devices Group Joint Annual Scientific Meeting of AAS/ Early Career Researcher Award ASBTE Young Investigator Award – AVBS/HBPRCA – Heart Research Institute Australian Nanotechnology Network Travel Award to attend International DR MELISSA FARNHAM Vascular Biology Meeting, Helsinki – DR STEVEN WISE High Blood Pressure Group Australian Atherosclerosis Society Applied Materials Group Carer’s Travel Scholarship – NSW Moderated Poster Award – Australian SMSFEIT – Biomedical Engineering Cardiovascular Research Network Atherosclerosis Society Collaboration Scheme, USYD

JUI CHIEN HUNG DR BENJAMIN RAYNER YUNJIA (CARMEN) ZHANG Applied Materials Group Inflammation Group Inflammation Group Best Oral Presentation, Josephine EMCR Oral Presentation Award – Society for Free Radical Research Travel Anderson Award – 34th Combined Cardiovascular Symposium, Award to present at the 19th Biennial Meeting Health Science Conference Cardiovascular Initiative of the Society-for-Free-Radical-Research- International (SFRRI), Lisbon, Portugal 46 2018 Heart Research Institute Annual Review

Select Conferences cell networks in the presence of “PACAP, Paul, and the productive years inflammation”. ISSHP & ISOM, of my PhD and post-doc”. Central and Presentations Amsterdam, Netherlands, October. Cardiovascular and Respiratory Control: Future Directions Scientific Meeting. “Effect of preventative low-dose aspirin Baker Heart and Diabetes Research treatment on experimental preeclampsia Institute, Melbourne, Australia, October. induced by TNF-α in pregnant mice”. 54th Invited Presentation. DR SIAN CARTLAND Australian and New Zealand Society of VASCULAR COMPLICATIONS GROUP Nephrology (ANZSN), Sydney, PROF BEN FREEDMAN “Targeting macrophages to reduce Australia, September. HEART RHYTHM AND STROKE PREVENTION GROUP inflammation and atherosclerosis”. PRADEEP CHOLAN “Atrial fibrillation and stroke: Sydney Cardiovascular Symposium, VASCULAR COMPLICATIONS GROUP underappreciated, unrecognized and under- Charles Perkins Centre, Sydney, “TRAIL protects against endothelial treated”. The Lui Che Woo Distinguished Australia, December. Invited Speaker. dysfunction in vivo and inhibits angiotensin- Professor Public Lecture, Chinese “TRAIL expressing monocyte/macrophages II-induced oxidative stress in vascular University of Hong Kong, Hong Kong, are critical for the prevention of endothelial cells in vitro”. Sydney China, October. inflammation and Atherosclerosis.” 20th Cardiovascular Symposium, Charles International Vascular Biology Meeting Perkins Centre, Sydney, Australia, “Roadmap for AF detection”. European 2018 (IVBM2018), Helsinki, Finland, June. December. Poster Presentation. Society of Cardiology; Official Satellite Symposium, Munich, Germany, August. Poster Presentation. “TRAIL protects against endothelial “TRAIL expressing monocyte/macrophages dysfunction in vivo and inhibits angiotensin- “Screening for asymptomatic AF in the are critical for reducing inflammation and II-induced oxidative stress in vascular population”. Heart Rhythm Society, Boston, atherosclerosis”. Joint Annual Scientific endothelial cells in vitro.” Arteriosclerosis, America, May. Featured Symposium. Thrombosis and Vascular Biology Meeting, Meeting of the AAS, AVBS and HBPRCA, “Smartphone electrographic monitoring San Francisco, USA, May. Adelaide, South Australia, November. for atrial fibrillation in acute ischemic PROFESSOR DAVID CELERMAJER “TRAIL protects against endothelial stroke and transient ischemic attack”. CLINICAL RESEARCH GROUP dysfunction in vivo and inhibits angiotensin- World Stroke Congress 2018, Montreal, “Early diagnosis of pulmonary hypertension”. II-induced oxidative stress in vascular Canada, October. endothelial cells in vitro”. Joint Annual Cardiac Society of ANZ, Brisbane, “Uncertainties in the management of atrial Scientific Meeting of the AAS, AVBS Australia, August. high rate episodes”. European Heart Rhythm and HBPRCA, Adelaide, South Australia, “Exercise and pulmonary hypertension”. Association; Official Satellite Symposium, November. Student Finalist. World Symposium on Pulmonary Barcelona, Spain, March. ALEXANDER DUPUY Hypertension, Nice, France, February. Chair of featured session on screening HAEMATOLOGY RESEARCH GROUP “Left atrial decompression, a novel heart for atrial fibrillation. American Heart “Control of platelet function by post- failure therapy”. Gaston Bauer Lecture at Association, Anaheim, USA, November. translational modification of alpha 2b beta Cardiac Society of ANZ, Brisbane, 3 integrin”. Joint Annual Scientific Meeting Three featured lectures on atrial fibrillation Australia, August. of the AAS, AVBS and HBPRCA, Adelaide, and moderator of one session, Asian “PFO Closure – State of the Art”. South Australia, November. Pacific Heart Rhythm Society, Taipei, Stroke Society of Australasia, Sydney, Taiwan, October. DR MELISSA FARNHAM Australia, August. HIGH BLOOD PRESSURE GROUP DR YEN CHIN KOAY ALEX CHAN “Effective data presentation at conferences”. CARDIOMETABOLIC DISEASE GROUP APPLIED MATERIALS GROUP ECR Workshop, Charles Perkins “New paradigms in type 2 diabetes “Interleukin-4 functionalised bioactive Centre, Sydney, Australia, March. treatment”. ANZMET 2018, University of vascular grafts modulate inflammation Invited Presentation. Auckland, Auckland, New Zealand, August. and inhibit neointimal hyperplasia,” “Intermittent PACAP induces “Novel circulating biomarkers identify insulin TERMIS World Congress, Kyoto, sympathoexcitation and is necessary resistance phenotypes in obesity”. ANZOS Japan, September. Oral Presentation. for the sympathetic response to 2018, Melbourne, Australia, October. DR KATRINA CHAU acute intermittent hypoxia”. Sydney “Novel therapeutic approaches to type VASCULAR IMMUNOLOGY GROUP Cardiovascular Symposium, Charles 2 diabetes and heart failure”. Sydney “Effect of preventative treatment with Perkins Centre, Sydney, Australia, Cardiovascular Symposium, Charles Perkins placental growth factor-2 on experimental December. Poster Presentation. Centre, Sydney, Australia, December. preeclampsia induced by TNF-α in pregnant “The role of PACAP in intermittent hypoxia “Novel therapeutic strategies in type mice”. ISSHP & ISOM, Amsterdam, induced sympathoexcitation”. Therapeutic 2 diabetes”. CVI Precision Medicine Netherlands, October. Intermittent Hypoxia Retreat, Florida, Symposium, Charles Perkins Centre, “Effect of placental growth factor on USA, April. Sydney, Australia, November. trophoblast integration into endothelial Select Conferences and Presentations

“Compression force sensing regulates in hypoglycaemia-associated autonomic integrin αIIbβ3 biomechanical adhesive failure (HAAF).” Central Cardiovascular function on diabetic platelets”. Joint Annual and Respiratory Control: Future Directions Meeting of Asian Biophysics Association Scientific Meeting, Baker Heart and (ABA) and Australian Society for Biophysics Diabetes Research Institute, Melbourne, (ASB), Melbourne, Australia, December. Australia, October. “Dual biomembrane force probe enables DR MARY KAVURMA single-cell mechanical analysis of signal VASCULAR COMPLICATIONS GROUP crosstalk between multiple molecular “TRAIL-expressing monocyte/macrophages species”. 62nd Annual Meeting of are critical for reducing inflammation and Biophysical Society, San Francisco, USA, atherosclerosis”. Baker Institute Seminar February 2018. Poster Presentation. Series, Melbourne, Australia, October. Invited Speaker. “From mechanical engineering to platelet mechanobiology”. Joint Annual Scientific SEUNG JAE KIM Meeting of the AAS, AVBS and HBPRCA, HIGH BLOOD PRESSURE GROUP Adelaide, South Australia, November. “Carotid body and subfornical organ AT1R- mediated sympathoexcitation following “Functional disulfides in platelet receptors”. SALLY GAO repetitive hypoxia requires intrarenal FASEB Science Research Conference: CARDIOVASCULAR MEDICAL ischemia in rats”. Experimental Biology, San Functional Disulfide Bonds in Health and DEVICES GROUP Diego, CA, USA, April. Poster Presentation. Disease, Leesburg, VA, USA, June. “Development of a microfluidic platform “Data blitz: Carotid body and subfornical “An intermediate state of integrin αIIbβ3 to study biomaterial thrombosis”. Sydney organ AT1R-mediated sympathoexcitation mediates platelet aggregation under Cardiovascular Symposium, Charles Perkins following repetitive hypoxia requires disturbed flow”. Mechanobiology Down Centre, Sydney, Australia, December. intrarenal ischemia in rats”. Therapeutic Under 2018, Sydney, Australia, May. PROFESSOR ANNEMARIE HENNESSY Intermittent Hypoxia Retreat, Florida, VASCULAR IMMUNOLOGY GROUP “Platelet flow chip: harness the force to USA, April. diagnose thrombotic tendency in patients “Update on preeclampsia”. Joint Annual DR RAHUL KURUP with diabetes”. Launch of ARC Training Scientific Meeting of the AAS, AVBS CELL THERAPEUTICS GROUP Centre for Innovative BioEngineering, and HBPRCA, Adelaide, South Australia, “Metabolomic profiling in chest pain patients Sydney, Australia, May. November. undergoing coronary angiography and “Obstetric emergencies”. Adelaide Critical ZOHRA KAKALL coronary sinus sampling”. Cardiac Society Care Conference (ACCCN), Adelaide, HIGH BLOOD PRESSURE GROUP of Australia and New Zealand 2018 annual South Australia, October. “Activation of μ-opioid receptors in the meeting, Adelaide, South Australia, August. rostral ventrolateral medulla blocks the Poster Presentation. “Using animal models to evaluate alpha- sympathetic counter-regulatory response BOB LEE 1-microglobulin (A1M) as a new potential to glucoprivation”. Australian Society for APPLIED MATERIALS GROUP pharmacological therapy for preeclampsia”. Medical Research Annual Conference, “A new method of plasma ion immersion EuroTox, Brussels, Belgium, September. NSW Teacher’s Federation Conference implantation: treating vascular grafts”. PROFESSOR SHAUN JACKSON Centre, Sydney, Australia, June. TERMIS World Congress, Kyoto, Japan, THROMBOSIS GROUP Poster Presentation. September. Poster Presentation. “Cardiovascular disease in the era of obesity “Activation of μ-opioid receptors in the JIALIN LI and diabetes: challenges and new frontiers”. rostral ventrolateral medulla blocks HEART RHYTHM AND STROKE Sydney Cardiovascular Symposium, the sympathetic counter-regulatory PREVENTION GROUP Charles Perkins Centre, Sydney, response to glucoprivation”. Experimental “Systematic review and meta-synthesis of Australia, December. Biology, San Diego, CA, USA, April. Poster qualitative literature on health professionals “Platelets and atherothrombosis”. Joint Presentation. experiences communicating with Chinese Annual Scientific Meeting of the AAS, “Generating a rodent model of Immigrants”. World Cardiology AVBS and HBPRCA, Adelaide, South hypoglycaemia unawareness to identify Conference, December. Australia, November. Invited Speaker. potential mechanisms underlying DR NICOLE LOWRES DR LINING (ARNOLD) JU the development of asymptomatic HEART RHYTHM AND STROKE THROMBOSIS GROUP hypoglycaemia”. Sydney Cardiovascular PREVENTION GROUP “Compression force sensing regulates Symposium, Charles Perkins Centre, “Atrial fibrillation risk factors and lifestyle integrin adhesive function on diabetic Sydney, Australia, December. workshop”. ACRA Annual Scientific Meeting, platelets”. Mechanobiology Down Poster Presentation. Brisbane, Australia, August. Under 2018, Sydney, Australia, May. “Reduced efferent neural drive following “Handheld ECG devices for detecting atrial Poster Presentation. endogenous opioid receptor activation fibrillation”. European Society Cardiology 48 2018 Heart Research Institute Annual Review

Congress, Munich, Germany, August. “The role of smooth muscle cells in vascular Medical Research, Sydney, Australia, October. “Incremental yield of annual ECG screening inflammation and atherosclerosis”. Joint DR FREDA PASSAM in a population in Japan without prior AF”. Annual Scientific Meeting of the AAS, AVBS HAEMATOLOGY RESEARCH GROUP American Heart Association Scientific and HBPRCA, Adelaide, South Australia, “NET-associated markers in heparin induced Sessions, Chicago, IL, USA, November. November. thrombocytopenia”. Blood, Brisbane, Australia, October. “Self-screening for secondary atrial DR POLINA NEDOBOY fibrillation”. ACRA Annual Scientific Meeting, HIGH BLOOD PRESSURE GROUP “Neutrophil activation and netosis are the Brisbane, Australia, August. “Microglial P2Y12R antagonism mediates key drivers of thrombosis in heparin- morphological changes but does not induced thrombocytopenia”. 60th Annual “Yield and stroke risk of screen-detected affect LPS-induced hypotension”. Central Meeting of the American Society of atrial fibrillation: a patient-level Cardiorespiratory Control: Future Directions Hematology, San Diego, CA, USA, December. meta-analysis”. Sydney Cardiovascular Annual Scientific Meeting, Melbourne, Symposium, Charles Perkins Centre, ASSOCIATE PROFESSOR SANJAY PATEL Australia, October. Poster Presentation. Sydney, Australia, December. CELL THERAPEUTICS GROUP “Short sustained, but not intermittent, “Colchicine – teaching an old drug new GRACE MACKIE hypoxia attenuates kainic acid-induced tricks”. Sydney Cardiovascular Symposium, CARDIOVASCULAR MEDICAL sympathetic nerve activity increase and Charles Perkins Centre, Sydney, Australia, DEVICES GROUP prevents seizure development in rats”. December. Invited Speaker. “Activation of FXII on immobilised Experimental Biology, San Diego, CA, liquid surfaces”. Sydney Cardiovascular “Use of optical coherence tomography in USA, April. Poster Presentation. Symposium, Charles Perkins Centre, 2018”. EPIC. Invited Speaker. Sydney, Australia, December. “A single short hypoxic episode decreases MANISHA PATIL PROFESSOR ANGELA MAKRIS kainic acid-induced sympathoexcitation VASCULAR COMPLICATIONS GROUP VASCULAR IMMUNOLOGY GROUP and attenuates seizure development in “TRAIL expressed by endothelial cells and “Effect of non-steroidal anti-inflammatory rats”. CCRCDF, Melbourne, Australia. pericytes is important for tubule formation drugs (NSAIDS) on post-operative Poster Presentation. and stabilisation in angiogenesis”. Sydney analgesia after caesarean section: “A single short hypoxic episode decreases Cardiovascular Symposium, Charles Perkins randomised controlled trial”. ISSHP & kainic acid-induced sympathoexcitation, Centre, Sydney, Australia, December. ISOM, Amsterdam, Netherlands, October. heart rate and attenuates seizure DHANYA RAVINDRAN “Placental growth factor reduces blood development in rats”. Sydney Cardiovascular VASCULAR COMPLICATIONS GROUP pressure in experimental preeclampsia”. Symposium, Charles Perkins Centre, Sydney, “Broad-spectrum chemokine inhibition Health Beyond Research Innovation Australia, December. Poster Presentation. blocks inflammation-induced pathological Showcase, South Western Sydney Local JESSICA ORCHARD angiogenesis but preserves hypoxia- Health District (SWSLHD), Sydney, HEART RHYTHM AND STROKE driven physiological angiogenesis”. Sydney Australia, June. PREVENTION GROUP Cardiovascular Symposium, Charles Perkins Centre, Sydney, Australia, December. “Using animal models to evaluate alpha- “High stroke risk of patients aged ≥65 years 1-microglobulin (A1M) as a new potential with screen-detected atrial fibrillation: “Broad-spectrum chemokine inhibition pharmacological therapy for preeclampsia”. collaboration and meta-analysis of 15 blocks inflammation-induced pathological EuroTox, Brussels, Belgium, September. screening studies”. CSANZ, Brisbane, angiogenesis but preserves hypoxia- Australia, August. driven physiological angiogenesis.” 20th PRAVEESUDA (JOY) MICHAEL International Vascular Biology Meeting APPLIED MATERIALS GROUP “Risk factors for muscle strains in Australian 2018 (IVBM2018), Helsinki, Finland, June. “Termis nanocarriers from plasma dust football: analysis of 3,700 muscle strains Poster Presentation. enhance gene delivery in diverse cell occurring in 270,000 AFL player matches”. types”. TERMIS World Congress, Kyoto, Sydney Muscoloskeletal Bone & Joint Health “Broad-spectrum chemokine inhibition Japan. September. Poster Presentation. Alliance Annual Scientific Meeting, Sydney, blocks inflammation-induced pathological Australia, November. Oral Presentation. angiogenesis but preserves hypoxia-driven DR ASHISH MISRA “Use of a smartphone electrocardiogram, physiological angiogenesis”. Joint Annual ATHEROSCLEROSIS AND electronic prompts and electronic decision Scientific Meeting of the AAS, AVBS VASCULAR REMODELLING GROUP support for atrial fibrillation screening in and HBPRCA, Adelaide, South Australia, “Clonal nature of SMC and role of integrin ß3 metropolitan general practice”. Sydney November. Mini Oral Student Finalist. in atherosclerosis”. Joint Annual Scientific Cardiovascular Symposium, Charles Perkins Meeting of the AAS, AVBS and HBPRCA, DR BENJAMIN RAYNER Centre, Sydney, Australia, December. Mini Adelaide, South Australia, November. INFLAMMATION GROUP Oral Presentation/Moderated Poster. Selenomethionine supplementation “Clonal nature of SMC and role of integrin DR JOHN O’SULLIVAN reduces lesion burden in a mouse model ß3 in vascular disease”. Harry Perkins CARDIOMETABOLIC DISEASE GROUP of atherosclerosis. Sydney Cardiovascular Institute of Medical Research, Perth, “Refining cardiometabolic disease”, Leaders in Symposium, Charles Perkins Centre, Western Australia, September. Science and Society, The Garvan Institute of Sydney, Australia, December. EMCR Oral Select Conferences and Presentations

Presentation Award Winner. NSW Australian Society for Medical Research (ASMR) Medical Research Week High Schools Career Day, June. Invited Speaker. UTS School of Life Sciences seminar program, October. Invited Speaker. DR MIGUEL SANTOS APPLIED MATERIALS GROUP “Plasma synthesis of nanoparticles for linker-free, spontaneous immobilization of bioactive cargo”. Australian Society for Biomaterials and Tissue Engineering, Perth, Australia, April. Oral Presentation. ASSOCIATE PROFESSOR SIMONE SCHOENWAELDER THROMBOSIS GROUP CPC EMCR Manuscript and Grant Reviewing Workshop, Charles Perkins Centre, The University of Sydney, Sydney, Australia, June. switch off inflammation”. Cardiovascular immobilized surface coatings”. TERMIS Multiple chair and assessor roles; Initiative Drug Discovery Symposium, World Congress, Kyoto, Japan, September. Joint meeting opening, Co-Chair joint Charles Perkins Centre, Sydney, Australia, opening session, Co-Chair Platelets and “Mechanisms of blood repellency on slippery, September. ECR Oral Presentation – Winner. Altherothrombosis, Assessor/Judge AVBS liquid-immobilised surface coatings.” Young Investigator/ECR moderated posters, “Developing biomaterial-based therapeutic Australasian Society for Biomaterials and Chair AVBS Young Investigator/ECR Oral applications for induced pluripotent stem Tissue Engineering (ASBTE), Perth, West Finalists, Co-Chair, AVBS Achievement and cell derived-endothelial cells using non- Australia, April. career development awards presentation, invasive bioluminescence imaging”. “Microfluidics for the evaluation of Australian Vascular Biology Society, TERMIS World Congress, Kyoto, Japan, immobilized liquid coatings”. Australia Adelaide, South Australia, November. September. Oral Presentation – Young and New Zealand Nano and Microfluidics Investigator Winner. DR RENUKA SHANMUGALINGAM (ANZNMF), Auckland, New Zealand, June. VASCULAR IMMUNOLOGY GROUP DR AMELIA TOMKINS DR STEVEN WISE “A biochemical assessment of compliance THROMBOSIS GROUP APPLIED MATERIALS GROUP vs resistance with aspirin therapy amongst “Plasminogen activation and extracellular “A new class of bioactive nanoparticles high-risk pregnant women: An analysis proteolysis”. Gordon Research Conference, for capable of spontaneous, linker-free against clinical outcomes”. Society of California, USA, February. Co-Chair. multifunctionalisation”. ComBio, Obstetric Medicine of Australia and New BRADLEY TUCKER Sydney, Australia, September. Zealand (SOMANZ), Cairns, Australia, July. CELL THERAPEUTICS GROUP Invited Oral Presentation. “A pharmacokinetic assessment of aspirin “Colchicine – a novel therapy for reducing “Developing new vascular materials: through timed analysis of plasma salicylate chemokine expression in ACS patients”. progress and challenges”. Cardiovascular acid level: an analysis of difference in Cardiac Society of Australia and New CVI Bioengineering workshop, Westmead gender, dose and preparation of aspirin”. Zealand 2018 annual meeting, Adelaide, Institute for Medical Research, Westmead, Society of Obstetric Medicine of Australia South Australia, August. Oral Presentation: Australia, April. Oral Presentation. and New Zealand (SOMANZ), Cairns, ISHR/CSANZ Student Prize for Best Free Australia, July. Communication Presentation 2018. “In vivo evaluation of next generation vascular materials”, Australia-China DR RICHARD TAN DR ANNA WATERHOUSE Conference of Tissue Engineering and APPLIED MATERIALS GROUP CARDIOVASCULAR MEDICAL Regenerative Medicine, Cairns, Australia, “Dual functionalised encapsulation DEVICES GROUP November. Keynote Speaker. platform for beta cell transplantation”. “Blood contacting medical devices”. ARC Australian Society for Biomaterials and Centre of Excellence for Electromaterials ERIC YANG Tissue Engineering, Perth, Australia, Science/Intelligent Polymer Research APPLIED MATERIALS GROUP April. Oral Presentation. Institute, University of Wollongong, “M-CSF-treated PLLA modulates Wollongong, Australia, October. inflammatory cytokines expression and “Next generation vascular materials that promotes angiogenesis”. TERMIS World “Blood repellency on slippery, liquid- Congress, Kyoto, Japan, September. Poster Presentation. 50 2018 Heart Research Institute Annual Review

Select brain network. Hum Brain Mapp. 2018 disease: A meta-analysis. Int J Cardiol. 2018 Dec;39(12):5028-5038. Dec 15;273:213-220. Publications Butera, D., Passam, F., Ju, L., Cook, K.M., Cao, L., Graham, S.L., Pilowsky, P.M. Woon, H., Aponte-Santamaría, C., Gardiner, Carbohydrate ingestion induces differential E., Davis, A.K., Murphy, D.A., Bronowska, autonomic dysregulation in normal-tension A., Luken, B.M., Baldauf, C., Jackson, glaucoma and primary open angle glaucoma. Akhavan, B., Michl, T.D., Giles, C., Ho, K., S., Andrews, R., Gräter, F., Hogg, P.J. PLoS One. 2018 Jun 7;13(6):e0198432. Autoregulation of von Willebrand factor Martin, L., Sharifahmadian, O., Wise, S.G., Carroll, L., Pattison, D.I., Davies, J.B., function by a disulfide bond switch. Coad, B.R., Kumar, N., Griesser, H.J., Bilek, Anderson, R.F., Lopez-Alarcon, C., Davies, Science Advances, 4(2). M.M. Plasma activated coatings with dual M.J. Superoxide radicals react with peptide- action against fungi and bacteria. Applied Callaghan, F., Maller, J.J., Welton, T., derived tryptophan radicals with very high Materials Today, 12:72–84. Middione, M.J., Shankaranarayanan, A., rate constants to give hydroperoxides as Barraclough, J.Y., Skilton, M.R., Garden, Grieve, S.M. Toward personalised diffusion major products. Free Radic Biol Med. 2018 F.L., Toelle, B.G., Marks, G.B., Celermajer, MRI in psychiatry: Improved delineation of Apr;118:126-136. fibre bundles with the highest-ever angular D.S. Early and late childhood telomere Celermajer, D.S. Atrial septal defects: resolution in vivo tractography. Transl length predict subclinical atherosclerosis Even simple congenital heart diseases can Psychiatry. 2018 Apr 25;8(1):91. at age 14 yrs – The CardioCAPS study. be complicated. Eur Heart J. 2018 Mar Int J Cardiol. 2019 Mar 1; 278:250-253. Callaghan, F.M., Grieve, S.M. Translational 21;39(12):999-1001. physiology: Normal patterns of thoracic Bautista, T.G., Fong, A.Y., Pilowsky, P.M., Chen, C., Wang, F., Wen, S., Su, Q.P., Wu, aortic wall shear stress measured using Ikeda, K., Kawakami, K., Spirovski, D., M.C.L., Liu, Y., Wang, B., Li, D., Shan, X., four-dimensional flow MRI in a large Onimaru, H. The expression of galanin in the Kianinia, M., Aharonovich, I., Toth, M., population. Am J Physiol Heart Circ parafacial respiratory group and its effects Jackson, S.P., Xi, P., Jin, D. Multi-photon Physiol. 2018 Nov 1;315(5):H1174-H1181. on respiration in neonatal rats. Neuroscience. near-infrared emission saturation nanoscopy 2018 Aug 1;384:1-13. Cannizzo, C.M., Adonopulos, A.A., using upconversion nanoparticles. Nature Bekendam, R.H., Iyu, D., Passam, F., Stopa, Solly, E.L., Ridiandries, A., Vanags, L.Z., Communications, (2018) 9:3290. Mulangala, J., Yuen, S.C.G., Tsatralis, T., J.D., De Ceunynck, K., Muse, O., Bendapudi, Chong, L.S.H., Fitzgerald, D.A., Craig, J.C., Henriquez, R., Robertson, S., Nicholls, P.K., Garnier, C.L., Gopal, S., Crescence, L., Manera, K.E., Hanson, C.S., Celermajer, D., S.J., Di Bartolo, B.A., Ng, M.K.C., Ting Chiu, J., Furie, B., Panicot-Dubois, L., Hogg, Ayer, J., Kasparian, N.A., Tong, A. Children’s Lam, Y., Bursill, C.A., Tan, J.T.M. VEGFR2 P.J., Dubois, C., Flaumenhaft R. Protein experiences of congenital heart disease: a is activated by high-density lipoproteins disulfide isomerase regulation by nitric oxide systematic review of qualitative studies. and plays a key role in the proangiogenic maintains vascular quiescence and controls Eur J Pediatr. 2018 Mar;177(3):319-336. thrombus formation. J Thromb Haemost. action of HDL in ischemia. FASEB J. 2018 Choteau, S.A., Cuesta Torres, L.F., 2018 Nov;16(11):2322-2335. Jun;32(6):2911-2922. Barraclough, J.Y., Elder, A.M.M., Martinez, Cao, J.Y., Lee, S.Y., Phan, K., Ayer, J., Biglari, S., Le, T.Y.L., Tan, R.P., Wise, S.G., G.J., Chen Fan, W.Y., Shrestha, S., Ong, K.L., Celermajer, D.S., Winlaw, D.S. Early Zambon, A., Codolo, G., De Bernard, M., Barter, P.J., Celermajer, D.S., Rye, K.A., outcomes of hypoplastic left heart syndrome Warkiani, M., Schindeler, A., Naficy, S., Patel, S., Tabet, F. Transcoronary gradients infants: meta-analysis of studies comparing Valtchev, P., Khademhosseini, A., Dehghani, of HDL-associated microRNAs in unstable the hybrid and Norwood procedures. World F. Simulating inflammation in a wound coronary artery disease. Int J Cardiol. J Pediatr Congenit Heart Surg. 2018 microenvironment using a dermal wound- 2018; 253:138-44. on-a-chip model. Advanced Healthcare Mar;9(2):224-233. Chung, K., Strange, G., Codde, J., Materials, 8, 1. Cao, J.Y., Lee, S.Y., Phan, K., Celermajer, Celermajer, D., Scalia, G.M., Playford, D.S., Lal, S. Renin-angiotensin-aldosterone Bobek, G., Stait-Gardner, T., Price, W.S., D. Left heart disease and pulmonary inhibition improves right ventricular function: Makris, A., Hennessy, A. Quantification hypertension: are we seeing the full picture?. a meta-analysis. Heart Asia. 2018 May of placental change in mouse models of Heart Lung Circ. 2018 Mar;27(3):301-309. preeclampsia using magnetic resonance 3;10(1):e010999. Clayton, Z.E., Tan, R.P., Miravet, M.M., microscopy. Eur J Histochem. 2018 Apr Cao, J.Y., Phan, K., Ayer, J., Celermajer, Lennartsson, K., Cooke, J.P., Bursill, C.A., 3;62(2):2868. D.S., Winlaw, D.S. Long term survival of Wise, S.G., Patel, S. Induced pluripotent hypoplastic left heart syndrome infants: Bonnitcha, P., Grieve, S., Figtree, G. stem cell-derived endothelial cells promote Meta-analysis comparing outcomes from Clinical imaging of hypoxia: Current status angiogenesis and accelerate wound closure the modified Blalock-Taussig shunt and the and future directions. Free Radic Biol Med. in a murine excisional wound healing model. right ventricle to pulmonary artery shunt. 2018 Oct;126:296-312. Biosci Rep. 2018 Jul 31;38(4). Int J Cardiol. 2018 Mar 1;254:107-116. Breukelaar, I., Williams, L.M., Antees, Cohen, E.M., Farnham, M.M.J., Kakall, Z., Cao, J.Y., Wales, K.M., Cordina, R., Lau, C., Grieve, S.M., Foster, S.L., Gomes, Kim, S.J., Nedoboy, P.E., Pilowsky, P.M. E.M.T., Celermajer, D.S. Pulmonary L., Korgaonkar, M.S. Cognitive ability is Glia and central cardiorespiratory pathology. vasodilator therapies are of no benefit in associated with changes in the functional Auton Neurosci. 2018 Nov;214:24-34. organization of the cognitive control pulmonary hypertension due to left heart Select Publications

D.J., Hornung, T., Grigg, L., Cordina, R., 2018 Feb 22; 2(1):10-15. d’Udekem, Y., Celermajer, D.S. Clinical Gatt, J.M., Burton, K.L.O., Routledge, K.M., outcomes in adolescents and adults after Grasby, K.L., Korgaonkar, M.S., Grieve, the Fontan procedure. J Am Coll Cardiol. S.M., Schofield, P.R., Harris, A.W.F., Clark, 2018;71(9):1009-17. C.R., Williams, L.M. A negative association Dissanayake, H.U., McMullan, R.L., Gordon, between brainstem pontine grey-matter A., Caterson, I.D., Celermajer, D.S., Phang, volume, well-being and resilience in healthy M., Raynes-Greenow, C., Skilton, M.R., twins. J Psychiatry Neurosci. 2018 Jun Polson, J.W. Noninvasive assessment of 20;43(5):170125. autonomic function in human neonates born Gerges, C., Gerges, M., Fesler, P., Maria at the extremes of fetal growth spectrum. Pistritto, A., Konowitz, N.P., Jakowitwsch, Physiol Rep. 2018 Apr;6(8):e13682. J., Celermajer, D.S., Lang, I.M. In-depth Dissanayake, H.U., McMullan, R.L., Kong, hemodynamic phenotyping of pulmonary Y., Caterson, I.D., Celermajer, D.S., Phang, hypertension due to left heart disease. Eur M., et al. Body fatness and cardiovascular Respir J. 2018 May 24;51(5). health in newborn infants. J Clin Med. Gu, Y., Doughty, R.N., Freedman, B., 2018 Sep; 7(9): 270. Kennelly, J., Warren, J., Harwood, M., Dupuy, A., Passam, F. Functional assays of Hulme, R., Paltridge, C., Teh, R., Rolleston, thiol isomerase ERp5. Methods in Molecular Cordina, R., Celermajer, D.S., d’Udekem, A., Walker, N. Burden of atrial fibrillation in Biology 2018. Y. Lower limb exercise generates pulsatile Mãori and Pacific people in New Zealand: flow into the pulmonary vascular bed in the Elias, P., Poh, C.L., du Plessis, K., Zannino, a cohort study. Intern Med J. 2018 setting of the Fontan circulation. Cardiol D., Rice, K., Radford, D.J., Bullock, A., Mar;48(3):301-309. Young. 2018 May;28(5):732-733. Wheaton, G.R., Celermajer, D.S., d’Udekem, Xu, X.R., Wang, Y., Reheman, A., Ju, L., Y. Long-term outcomes of single-ventricle Cordina, R., Ministeri, M., Babu-Narayan, Spring, C.M., Jin, J.W., Yang, H., Neves, M., palliation for pulmonary atresia with intact S.V., Ladouceur, M., Celermajer, D.S., Chen, P., Yang, Y., Lei, X., Chen, Y., Zhang, ventricular septum: Fontan survivors remain Gatzoulis, M.A., Uebing, A., Li, W. Evaluation H., Song, J., Ke, P., Zhang, D., Zhu, G., She, at risk of late myocardial ischaemia and of the relationship between ventricular end- Y-M., Cyr, T., Fu, W., Liu, G., Connelly, P.W., death. Eur J Cardiothorac Surg. 2018 Jun diastolic pressure and echocardiographic Rand, M.L., Adeli, K., Freedman, J., Lee, 1;53(6):1230-1236. measures of diastolic function in adults J.E., Tso, P., Marchese, P., Zhu, C., Davidson, with a Fontan circulation. Int J Cardiol. Filipe, E.C., Santos, M., Hung, J., Lee, W.S., Jackson, S.P., Ruggeri, Z.M. and Ni, 2018 May 15;259:71-75. B.S.L., Yang, N., Chan, A.H.P., Ng, M.K.C., H. Apolipoprotein A-IV is a novel ligand of Rnjak-Kovacina, J., Wise, S.G. Rapid platelet aIIbß3 integrin and an endogenous Daly, A., Robertson, A., Johnston, P., endothelialization of off-the-shelf small inhibitor of thrombosis. Nature Commun. Middleton, S., Bobek, G., Sullivan, C., diameter silk vascular grafts. JACC Basic Sep 6; 9(1):3608. doi: 10.1038/s41467-018- Hennessy, A. Sleep disordered breathing Transl Sci. 2018 Mar 1;3(1):38-53. 05806-0 and sFlt-1 controlled by CPAP in a patient with chronic hypertension in pregnancy. Freedman, B. Major progress in Harmer, J.A., Keech, A.C., Veillard, A.S., Obstet Med. 2018 Mar;11(1):32-34. anticoagulant uptake for atrial fibrillation at Skilton, M.R., Watts, G.F., Celermajer, last: Does it translate into stroke prevention?. D.S. Fenofibrate effects on carotid artery Daly, A.L., Sriram, N., Woodall, C., Eur Heart J. 2018 Aug 21;39(32):2984-2986. intima-media thickness in adults with type Selvakumar, K., Briggs, K., Garg, P., Russell, 2 diabetes mellitus: A FIELD substudy. L., Yu, M., Beetson, K., Hennessy, A., on Freedman, B., Schnabel, R., Calkins, H. Diabetes Res Clin Pract. 2018 Jul;141: behalf of Tharawal AMS Board. Risk factors Opportunistic electrocardiogram screening 156-167. associated with hypertensive disorders of for atrial fibrillation to prevent stroke. pregnancy within an urban Indigenous JAMA Cardiol. 2018 Dec 26. doi: 10.1001/ Hourigan, S.T., Solly, E.L., Nankivell, V.A., population in south western Sydney. jamacardio.2018.4335. Ridiandries, A., Weimann, B.M., Henriquez, Intern Med J. 2018 Mar; 48(3):269-275. 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force sensing regulates integrin αiIbß3 S.M. 4D flow magnetic resonance imaging: Lane, D.A., Ruff, C.T., Turakhia, M., adhesive function on diabetic platelets. role in pediatric congenital heart disease. Werring, D., Patel, S., Moores, L. Nat Commun. 2018 Mar 14;9(1):1087. Asian Cardiovasc Thorac Ann. 2018 Antithrombotic therapy for atrial fibrillation: Jan;26(1):28-37. CHEST guideline and expert panel report. Kakall, Z.M., Cohen, E.M., Farnham, M.M.J., Chest. 2018 Nov;154(5):1121-1201. Kim, S.J., Nedoboy, P.E., Pilowsky, P.M. Lee, K.H., Cavanaugh, L., Leung, H., Yan, Integration of hindbrain and carotid body F., Ahmadi, Z., Chong, B.H., Passam, F. Lowres, N., Mulcahy, G., Jin, K., Gallagher, mechanisms that control the autonomic Quantification of NETs-associated markers R., Neubeck, L., Freedman, B. response to cardiorespiratory and glucoprivic by flow cytometry and serum assays in Incidence of postoperative atrial fibrillation insults. 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Am J Physiol Regul Immunohistochemical expression of the Integr Comp Physiol. 2018 Dec nicotinic acetylcholine receptor (nAChR) 1;315(6):R1115-R1122. subunits in the human placenta, and effects of cigarette smoking and preeclampsia. Kakall, Z.M., Pilowsky, P.M., Farnham, Placenta. 2018 Nov;71:16-23. M.M.J. PACAP-(6–38) or kynurenate microinjections in the RVLM prevent the Mackie, G., Gao, L., Yau, S., Leslie, D.C., development of sympathetic long-term Waterhouse, A. Clinical potential of facilitation after acute intermittent hypoxia. immobilized liquid interfaces: perspectives Am J Physiol Heart Circ Physiol. 2018 Mar on biological interactions. Trends in 1;314(3):H563-H572. Biotechnology, 37(3), 268-280. Kim, S.J., Fong, A.Y., Pilowsky, P.M., Maclean, J.A., Schoenwaelder, S.M. Abbott, S.B.G. 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Biol Psychiatry Cogn Neurosci and cultural sensitivity of linguistically Increased hippocampal tail volume predicts Neuroimaging. 2018 Aug 31. pii: S2451- appropriate cardiovascular disease depression status and remission to anti- 9022(18)30236-2. information for Chinese immigrants: depressant medications in major depression. Kulkarni, K., Hung, J., Fulcher, A.J., Chan, a review of online resources from Heart Mol Psychiatry. 2018 Aug;23(8):1737-1744. Foundations. J Cardiovasc Nurs. 2018 A.H.P., Hong, A., Forsythe, J.S., Aguilar, Manuneedhi Cholan, P., Cartland, S.P., May/Jun;33(3):269-280. M.-I., Wise, S.G., Del Borgo, M.P. Dang, L., Rayner, B.S., Patel, S., Thomas, ß3-Tripeptides coassemble into fluorescent Li, Z., Ju, X., Lee, K., Clarke, C., Hsu, S.R., Kavurma, M.M. TRAIL protects hydrogels for serial monitoring in vivo. J.L., Abadir, E., Bryant, C.E., Pears, S., against endothelial dysfunction in vivo and ACS Biomater. Sci. 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Martínez, G.J., Celermajer, D.S., Patel, S. A., Rogers, K., Redfern, J. Choice of Health osteoarthritis treatments, not effective ones. The NLRP3 inflammasome and the emerging Options In prevention of Cardiovascular Aust Health Rev. 2018 Mar 20. doi: 10.1071/ role of colchicine to inhibit atherosclerosis- Events (CHOICE) Replication Study. Heart AH17131. associated inflammation. Atherosclerosis. Lung Circ. 2018 Dec;27(12):1406-1414. Pan, G.J., Rayner, B.S., Zhang, Y., van 2018 Feb;269:262-271. Ngo, T.H.L., Vu, V.B., Nguyen, C.H., Le, Reyk, D.M., Hawkins, C.L. A pivotal role Melehan, K.L., Hoyos, C.M., Hamilton, G.S., T.D., Hoang, T.K., Freedman, B., Lowres, for NF-κB in the macrophage inflammatory Wong, K.K., Yee, B.J., McLachlan, R.I., N. Identification of new-onset atrial response to the myeloperoxidase oxidant O’Meagher, S., Celermajer, D., Ng, M.K., fibrillation after cardiac surgery in Vietnam. hypothiocyanous acid. Arch Biochem Grunstein, R.R., Liu, P.Y. 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Santos, M., Waterhouse, A., Lee, B. prevalence of atrial fibrillation in rural patients with cyanotic congenital heart S-L., Chan, A.H.P., Tan, R.P., Michael, Western India: results of SMART-India, a disease. Int J Cardiol. 2019 Feb 15;277: P.L., Filipe, E., Hung, J., Wise, S.G. population-based screening study. Int J 97-103. and Bilek, M.M.M. ‘Simple one-step Cardiol. 2019 Apr 1;280:84-88. Thompson, P.L., Mark Nidorf, S. Anti- covalent immobilization of bioactive Spencer, L., Zafiropoulos, B., Denniss, W., inflammatorytherapy with canakinumab agents without use of chemicals on Fowler, D., Alison, J., Celermajer, D. Is for atherosclerotic disease: Lessons from plasma-activated low thrombogenic there a learning effect when the 6-minute the CANTOS trial. J Thorac Dis. 2018 stent coatings’ In: Functionalised walk test is repeated in people with Feb;10(2):695-698. Cardiovascular Stents (Podbielska, suspected pulmonary hypertension? 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pulmonary pressures and right heart failure: Witsch, J., Merkler, A.E., Chen, M.L., Navi, She, Y.-M., Cyr, T., Fu, W., Liu, G., Connelly, a systematic review and meta-analysis. Eur B.B., Sheth, K.N., Freedman, B., Schwamm, P.W., Rand, M.L., Adeli, K., Freedman, J., Heart J. 2019 Feb 1;40(5):476-484. L.H., Kamel, H. Incidence of atrial Lee, J.E., Tso, P., Marchese, P., Davidson, fibrillation in patients with recent ischemic W.S., Jackson, S.P., Zhu, C., Ruggeri, Z.M., Waterhouse, A., Leslie, D.C., Bolgen, D., stroke versus matched controls. Stroke. Ni, H. Apolipoprotein A-IV binds IIbß3 Berthet-Hicks, J., Donovan, K., Super, M., α 2018 Oct;49(10):2529-2531. integrin and inhibits thrombosis. Nat Nedder, A., Ingber, D.E. Modified clinical Commun. 2018 Sep 6;9(1):3608. monitoring assessment criteria for multi- Wong, J., Chabiniok, R., Tibby, S.M., organ failure during bacteremia and sepsis Pushparajah, K., Sammut, E., Celermajer, Yan, B.P., Lai, W.H.S., Chan, C.K.Y., Chan, progression in a pig model. Advan Crit Care D.S., Giese, D., Hussain, T., Greil, G.F., S.C.-Hin., Chan, L.-H., Lam, K.-M., Lau, Med 2018; 1:002. Schaeffter, T., Razavi, R. Exploring kinetic H.-W., Ng, C.-M., Tai, L.-Y., Yip, K.-W., To, Waterhouse, A., Leslie, D.C., Lightbown, K., energy as a new marker of cardiac function O.T.L., Freedman, B., Poh, Y.C., Poh, M.-Z. Antonoff, D., Lightbown, S., Dimitrakakis, N., in the single ventricle circulation. J Appl Contact-free screening of atrial fibrillation Hicks-Berthet, J.B., Leslie, C.N., Super, M., Physiol (1985). 2018 Sep 1;125(3):889-900. by a smartphone using facial pulsatile photoplethysmographic signals. J Am Ingber, D.E., Ackerman, MB. Rapid coating Wong, N.K.P., Cheung, H., Solly, E.L., Heart Assoc. 2018 Apr 5;7(8). process generates omniphobic dentures in Vanags, L.Z., Ritchie, W., Nicholls, S.J., minutes to reduce c. albicans biofouling. Ng, M.K.C., Bursill, C.A., Tan, J.T.M. Yeung, K.R., Sunderland, N., Lind, J.M., ACS Biomater. Sci. Eng. 2019, 5, 2, 420-424. Exploring the roles of CREBRF and TRIM2 Heffernan, S., Pears, S., Xu, B., Hennessy, Watson, E.E., Liu, X., Thompson, R.E., in the regulation of angiogenesis by high- A., Makris, A. Increased salt sensitivity Ripoll-Rozada, J., Wu, M., Alwis, I., Gori, density lipoproteins. Int J Mol Sci. 2018 in offspring of pregnancies complicated A., Loh, C.-T., Parker, B.L., Otting, G., Jun 28;19(7). by experimental preeclampsia. Clin Exp Pharmacol Physiol. 2018 Dec;45(12): Jackson, S., Pereira, P.J.B., Payne, R.J. Wong, N.K.P., Nicholls, S.J., Tan, J.T.M., 1302-1308. Mosquito-derived anophelin sulfoproteins Bursill, C.A. The role of high-density are potent antithrombotics. ACS Cent. Sci. lipoproteins in diabetes and its vascular Yu, C., Moore, B.M., Kotchetkova, I., 2018, 4, 4, 468-476. complications. Int J Mol Sci. 2018 Cordina, R.L., Celermajer, D.S. Causes Wilson, T.G., d’Udekem, Y., Winlaw, D.S., Jun 5;19(6). of death in a contemporary adult congenital heart disease cohort. Heart. Cordina, R.L., Celermajer, D.S., Wheaton, Xu, X.R., Wang, Y., Adili, R., Ju, L., Spring, 2018 Oct;104(20):1678-1682. G.R., et al. Hepatic and renal end-organ C.M., Jin, J.W., Yang, H., Neves, M.A.D., damage in the Fontan circulation: A report Chen, P., Yang, Y., Lei, X., Chen, Y., Gallant, from the Australian and New Zealand R.C., Xu, M., Zhang, H., Song, J., Ke, P., Fontan Registry. Int J Cardiol. 2018 Dec Zhang, D., Carrim, N., Yu, S.-Y., Zhu, G., 15;273:100-107. 56 2018 Heart Research Institute Annual Review

Board of Governors

The Board of Governors is chaired by Professor Len Kritharides and comprises deans from medical schools, nominees from Dr Teresa Anderson AM The Sydney Local Health District, affiliates of The University of B App Science (Speech Pathology) PhD Sydney, leaders from the corporate sector, and the Director of Cardiovascular Research of the Heart Research Institute. The Board is responsible for the governance of the Heart Research Dr Teresa Anderson is the Chief Executive Institute. It approves and monitors budgets and scientific of Sydney Local Health District, one of the progress. Members are balanced to represent the corporate leading public health services in Australia. and scientific community. The majority of the Board positions She has more than 35 years of experience as a clinician and health are available to be filled via election by the members of the service executive. She has a well-established reputation for incorporated company, the Heart Research Institute Ltd. implementing strategies to foster innovation and best practice, supporting collaboration and building partnerships. She is an internationally recognised speech pathologist and is passionate CHAIRMAN about developing programs and services to support and improve Professor Len Kritharides the health and wellbeing of all people in the community. In 2018, MBBS PhD FRACP FAHA FCSANZ FESC FACC Dr Anderson was appointed a Member of the Order of Australia (AM). Dr Anderson is a member of seven medical research, health and primary health network boards, and is an active member of Professor Len Kritharides is Senior Staff the Sydney Health Partners Governing Council and Executive Specialist and Head of the Department Management Group, one of the first four centres in Australia of Cardiology at Concord Repatriation designated by the National Health and Medical Research Council General Hospital (CRGH) Sydney, Conjoint Professor in Medicine (NHMRC) as an Advanced Health Research Translation Centre. at The University of Sydney, Head of the Atherosclerosis Research Laboratory Group at the ANZAC Research Institute and Deputy Clinical Director of the Cardiovascular Stream of the Sydney Local Health District. In 1994, he completed a PhD in macrophage biology at HRI. After postdoctoral research at HRI and in the USA, he took up an appointment as Staff Specialist in Cardiology at CRGH in 1998 and became Head of Department in 2003. Professor Kritharides was awarded a NSW Government Community Services Award for his contribution to CRGH in Mrs Sandra Boswell 2006, the President’s Medal for contributions to the Cardiac BEC (Syd) FCA MAICD Society of Australia and New Zealand (CSANZ) in 2013, and the Distinguished Researcher Award by the Australian Vascular Mrs Sandra Boswell has over 25 years Biology Society in 2014. He is currently President of CSANZ, Chair of experience as a specialist working with of the Specialist Training Committee in Cardiology of the Royal companies who undertake innovation in Australian College of Physicians and a Director and National Australia, assisting them with seeking Government grants and Board Member of the Heart Foundation of Australia. He was funding to undertake novel projects. Mrs Boswell was a partner appointed to the Board of the HRI in 2009, Chairs its Scientific for 15 years with PwC Australia, retiring in 2018. During that time, Advisory Committee, and was appointed Chairman in 2017. she led businesses within PwC and was also a member of the Australian Governance Board of Partners for several years. She chaired the Finance and Operations (Audit) Committee whilst on Mr John Batistich the Board and was a member of several other committees. In 2017 BBUS MMGT GAICD she was appointed as a member of the PwC Asia Pacific Board. She is currently a Director and National Leader of Innovation and Incentives at Glasshouse Advisory, part of the Xenith IP group Mr John Batistich is a Non-Executive working with companies across sectors on their innovation strategies Director of Zip Co Limited, General Pants and assisting them in seeking both direct and indirect Government Group and FoodCo. He has more than funding. Mrs Boswell has worked with the Australian Government 26 years of experience in consumer research, marketing, digital with regard to innovation policy and administration and has assisted innovation and general management with blue chip companies with the drafting of legislation and policy on attracting innovation including Westfield, Wrigley, Pepsico and Kimberly Clark. Mr Batistich investment to the country. She believes that innovation is vital to holds a Masters in Management degree from Macquarie Graduate a healthy robust economy. She has worked with companies in the School of Management majoring in Human Resources, a Bachelor digital economy and health sector, particularly in relation to the of Business degree from the University of Western Sydney majoring development of new technologies in this sector. Mrs Boswell is in Marketing, Certificate in Digital Marketing from the Association also currently a Non-Executive Director of GLEIF and the Sisters for Data-driven Marketing and Advertising, and is a Graduate of the of Charity Foundation. She has a Bachelor of Economics Australian Institute of Company Directors. (social sciences) from The University of Sydney. Board of Governors

Professor Andrew Boyle Mr Barry Brownjohn MBBS (HONS) FRACP PhD BCOMM

Professor Andrew Boyle is currently Mr Barry Brownjohn is an experienced Professor of Cardiovascular Medicine, banking and finance executive whose Clinical Dean of the Hunter Clinical skill sets include capital markets, risk School of the University of Newcastle and a practising management, corporate advisory and business planning. interventional cardiologist. He has over 100 career journal His senior executive roles have included capital markets and publications, eight book chapters and three patents. Andrew investment banking businesses in Asia, North America and in heads both a clinical and a basic science research team. He Australia, serving as Managing Director of Bank of America. started studying left ventricular (LV) remodelling as the subject Utilising his extensive industry experience and understanding of his PhD (2002-5) and has continued in this field ever since. of technology in financial services, he has served as an advisor He has considerable experience in rodent models, porcine to incumbent industry participants and new businesses seeking models and human clinical trials. While his laboratory continues to bring innovative business models and enabling technologies to study in vitro and preclinical models of cardiac fibrosis, LV into the market. Non-Executive Director roles have included remodelling and cardiac regeneration, he is also international Citigroup Pty Ltd, Dexus Property Group, Bakers Delight Holdings principal investigator on a clinical trial of a novel drug for post- Pty Limited and The South Australian Financing Authority. infarction LV remodelling, conducted at over 15 sites world-wide. Mr Brownjohn has a Bachelor Degree in Accounting Finance His clinical research focuses on acute coronary syndromes, and Systems from the University of New South Wales. including novel risk stratification parameters and optimising treatment strategies especially in rural and remote locations.

Mr Rod Halstead Professor Shaun Jackson LLB (Syd) LLM (Lon) FAICD MBBS (Hons) BMedSci (Hons) PhD

Mr Halstead is presently Director – Professor Shaun Jackson is an NHMRC Strategic Corp/M&A at the law firm Senior Principal Research Fellow and Clayton Utz. Prior to holding that position faculty member at the prestigious Scripps he had many years’ experience as a Partner at Clayton Utz, with Research Institute in La Jolla, San Diego (CA, USA). He established a preceding position at the law firm Mallesons Stephen Jaques. his independent research laboratory in the Monash Department Mr Halstead has considerable Board experience and regularly of Medicine at Box Hill Hospital in Victoria (1998–2003). In advises Boards and Senior Management of major Australian 2004 he moved to the Alfred Medical Research and Education corporate and financial institutions, in respect to business and Precinct, where he co-founded and became Research Director governance related matters. of the Australian Centre for Blood Diseases. He is a founder of Kinacia, an Australian biotechnology company developing novel diagnostic and therapeutic products aimed at preventing blood clotting. In 2013, Professor Jackson was appointed the inaugural Director of Cardiovascular Research, Heart Research Institute and Charles Perkins Centre, The University of Sydney. He is also Research Director of Atherothrombosis Services within the Department of Cardiology at the Royal Prince Alfred (RPA) hospital. Professor Jackson’s research interests are focused in the area of atherothrombosis and cardiovascular disease. In 2018, Professor Jackson received the NSW Ministerial Award for Cardiovascular Research Excellence. 58 The2018 2018 Heart Heart Research Research Institute Annual Annual Review Review

Mr Richard Rassi Ms Cath Rogers BCOM (UNSW) FCA GAICD BCOM MBA CFA GAICD

Mr Richard Rassi is a chartered accountant, Ms Cath Rogers is Non-Executive having spent most of his career working Director of ASX-listed AUB Group Limited at Deloitte and as a partner in the firm up and Beem It, a collaborative payments to December 2011. He now operates a consulting practice (Riclin venture between Westpac, Commonwealth Bank and NAB, Consulting) providing consulting services in the areas of strategy, and was previously a Non-Executive Director of McGrath Limited. governance, risk management, audit and financial reporting. Richard Ms Rogers is a Director and Co-Founder of the Digital Receipt also mentors a number of senior professionals and executives. Exchange and has held senior roles in venture capital, private equity He continues to be retained by Deloitte to assist with the delivery and financial services firms in Australia and overseas, including of services to clients including providing a quality assurance role AirTree Ventures, Anchorage Capital Partners, Masdar Capital on a range of audit and advisory engagements. Complementing and Credit Suisse. Ms Rogers holds a Bachelor of Commerce from this expertise are various governance roles including as director the University of New South Wales, an MBA from INSEAD, is a and audit committee chair of various retail superannuation boards CFA charterholder and a graduate of the Australian Institute of operating within National Australia Bank (August 2012 to May Company Directors. 2014) and as a member of the audit and finance committee for the Australian Broadcasting Corporation (current appointment). He also currently serves as a member of the Disciplinary Tribunal of Chartered Accountants Australia and New Zealand. Richard maintains an active involvement with the Australian Institute of Company Directors and has assisted the AICD with the development of their various director education programs. This has included authoring a course on strengthening financial governance and delivering webinars on year-end financial reporting obligations for directors and governance related topics.

Professor Stephen Simpson AC Professor Wendy Jessup FAA FRS BSC PHD

Professor Stephen Simpson is Academic Professor Wendy Jessup completed her Director of the Charles Perkins Centre, tertiary scientific training at the Universities a University of Sydney cross-faculty of Manchester and Sheffield in the United initiative aimed at researching and implementing cross-disciplinary Kingdom. She moved to Australia in 1989 to take up a position approaches to alleviating the burden of obesity, diabetes, at HRI. She was promoted to leader of the Cell Biology Group in cardiovascular disease and related conditions. He is also the 1994, later also becoming Deputy-Director until shortly before Executive Director of Obesity Australia. After completing an her departure in 2002. Until the end of 2012 she was a Principal undergraduate degree at the University of Queensland, he pursued Research Fellow at the National Health and Medical Research a PhD at the University of London. Professor Simpson spent 22 Council (NHMRC) and a Professor and Principal Research Fellow years at the University of Oxford, first in Experimental Psychology, in the Faculty of Medicine at the University of New South Wales, then in the Department of Zoology and the Oxford University where she co-led the Macrophage Biology Group at the Centre Museum of Natural History. He returned to Australia in 2005 as for Vascular Research. She is now a Principal Research Fellow in an Australian Research Council (ARC) Federation Fellow, then ARC the Atherosclerosis Laboratory at the ANZAC Research Institute. Laureate Fellow. In 2007 Professor Simpson was elected a Fellow Professor Jessup stepped down from the Board of Governors of of the Australian Academy of Science, and in 2013 he was elected HRI on 23 May 2018. a Fellow of the Royal Society of London as “one of the world’s foremost entomologists and nutritional biologists”. In 2015 he was made a Companion of the Order of Australia “for eminent service to biological and biomedical science.” Board of Governors | International Board of Governors

International Board Kerry Cunningham In 1995, he joined Visa in London, becoming Kerry Cunningham is the Director of General Counsel and a member of the of Governors Business Integration for Blackmores, excom of Visa CEMEA in 1996. He Australia’s number one vitamin and dietary subsequently became Head of Risk and supplement company. Kerry has over 25 Legal Affairs in 2000. Adrian moved to San years’ experience in the pharmaceutical and Francisco in 2007, where he became Deputy Tony Pollitt (Chair) health industry working in Australia, New Chief Risk Officer and was a member of the BECON (MACQ) MBA (UNE) FCA Zealand, UK, Thailand and China. Kerry has excom of Visa Inc. In 2010, Adrian joined Tony Pollitt is the Director – Business an extensive career at Blackmores in senior Amadeus as Head of Legal IT and Privacy Affairs, Movies at Foxtel, the Australian leadership positions driving the change based in Madrid and subsequently Nice. subscription television network. Tony agenda and supporting the growth of the qualified as a Chartered Accountant in business. Additionally she has held board He is today General Counsel for 441 Trust 1989 and worked for Coopers & Lybrand positions with Complimentary Medicines Company Limited, a company representing in Sydney and London. In 1998, Tony Australia and UTS Faculty of Pharmacy the interests of many banks in Europe in was appointed Chief Operating Officer Advisory Board. relation to their sale of Visa Europe to Visa responsible for the finance and internal Inc for c. $20 billion dollars. Adrian is also operations of Showtime. Tony currently Dr Stephen Hollings on the Advisory Board of Brighton University manages a Foxtel team that negotiates BA (HONS) PhD FAICD Business School, is a Governor of Queens the content supply arrangements for movie Dr Stephen Hollings is CEO of the Heart Park Primary School and is a Non-Executive and external channel partners, and works Research Institute. He is a senior executive Director of Americio SICAV, a Spanish with Foxtel’s production team to structure and non-executive director with extensive investment company. contracts for locally produced shows. experience in highly competitive, customer- driven industries. He has successfully led Elena Pintado John Batistich businesses through periods of growth and BCOM BBUS MMGT GAICD development as well as through times of Elena Pintado is Director, Brand Development John Batistich is a Non-Executive Director unprecedented change created by economic for Newell Brands, a $13bn global of Zip Co Limited, General Pants Group turbulence, industry restructuring and consumer goods company. In her role, and FoodCo. He has more than 26 years disruptive technology. In his various Chair, Elena leads marketing for the Appliances of experience in consumer research, CEO and senior executive roles he has and Cookware division in APAC region. The marketing, digital innovation and general become known for providing a strong focus role encompasses innovation development, management with blue chip companies on and a personal commitment to the brand strategy and communications for including Westfield, Wrigley, Pepsico and development of emerging leaders, providing brands such as Sunbeam and Crock-Pot. Kimberly Clark. John holds a Masters organisations with a robust talent pipeline. Elena is a marketing professional with more in Management degree from Macquarie He has played a key role as an executive than 15 years’ experience in the FMCG, Graduate School of Management majoring coach and mentor for over 20 years. consumer goods and healthcare industries. in Human Resources, a Bachelor of Business Her previous roles have included Marketing degree from the University of Western Stephen Moodey Manager at Johnson & Johnson responsible Sydney majoring in Marketing, Certificate BBUS MBA CPA for the Women’s Health portfolio, as in Digital Marketing from the Association Stephen Moodey is the Area Finance well as with GlaxoSmithKline Consumer for Data-driven Marketing and Advertising Director for GlaxoSmithKline Consumer Healthcare where Elena worked for seven and is a Graduate of the Australian Institute Healthcare Australia and New Zealand, years developing award-winning marketing of Company Directors. providing decision support to the division’s campaigns for products such as Nicabate, General Manager across strategic, financial Panadol, Sensodyne, Cartia and Zovirax. Alan Caton OBE and operational dimensions. He has more Elena holds a Bachelor of Commerce from Alan is currently the Independent Chairman than 20 years’ experience as a financial the University of New South Wales, majoring of Islington and Central Bedfordshire professional in the delivery of financial in Marketing and International Business. Safeguarding Children Boards, a role that processes, reporting, analytics and sees him coordinate the efforts of all the business partnering, forecasting and budget Sathy Sappany agencies represented on the Board to development. Stephen holds a Masters in BCOM ACMA CPA achieve effective safeguarding, and to Business Administration (Executive) from the Sathy Sappany was Head of Finance at the ensure that children and young people Australian Graduate School of Management, Heart Research Institute Ltd, as well as a are being successfully protected within is a member of the Australian Society of member of CPA Australia and the Chartered the wider partnership. Certified Practising Accountants and holds Institute of Management Accounts in the a Bachelor of Business degree from the UK. Sathy has over 20 years’ experience in In 2012 Alan was awarded an OBE by University of Technology, Sydney majoring senior Finance and Business Management Her Majesty the Queen, for his services in Accounting and Finance. positions, providing strategic decision to policing. Alan is also a Local support to Boards specially in the not-for- Government Association peer reviewer Adrian Phillips profit sector. and the independent chair of the North BA (HONS) London Sector Steering Group, which is Adrian Phillips started his career at Simmons implementing the findings of a Child & Simmons in the corporate department Sexual Abuse review and developing the where he concentrated on mergers and Honorary Solicitor: Patricia Paton concept of the ‘Child House’ across London. acquisitions, joint ventures and insolvency. Company Secretary: Hana Krskova 60 2018 Heart Research Institute Annual Review

Members of the Institute

MEMBERS OF Dr Richard Dunn Mr Frank Lowy AO THE INSTITUTE MBBS FRACP FACC Mr Robert Miller AM Mr John Fairfax AO Prof David Allen Assoc Prof Lynne Pressley MBBS PHD FAA Prof Peter Fletcher MBBS (HONS) BMEDSCI MBBS PHD FRACP (HONS) DPHIL FRACP Dr Teresa Anderson AM B APP SCIENCE Mr Michael Ford Mr Richard Rassi (SPEECH PATHOLOGY) PHD BCOM (UNSW) FCA GAICD Prof Ben Freedman OAM Dr Brian Bailey FACC FAHA FCSANZ FESC Dr John Richards MBBS FRACP FACC FRACP MBBS PHD Prof David Richmond AM Dr Ian Bailey Emeritus Prof Carolyn Geczy MB CHB MSC FRACP MBBS FRACP FACC PHD FRCP FACC

Mr James Bain AM Mr Chris Hadley Ms Cath Rogers BA FSIA BCOM MBA CFA GAICD Mrs Phillippa Baird Mr Rod Halstead Ms Mary Salteri-Shaw Prof Philip Barter LLB (SYD) LLM (LON) FAICD MBBS PHD FRACP Dr Laurie Scandrett Prof Phillip Harris AM Mr John Batistich Dr Brian Scott AO BSC MBBS DPHIL FRACP CHANGES TO THE BBUS MMGT GAICD FACC Prof Stephen Simpson AC BOARD OF GOVERNORS Mr Marcus Blackmore AM FAA FRS Dr Stephen Hollings Mrs Sandra Boswell Mrs Sandra Boswell BA (HONS) PHD FAICD Mr David Smithers AM BEC (SYD) FCA MAICD BEC (SYD) FCA MAICD FCA FICD Dr Philip Hoyle Prof Andrew Boyle Prof Andrew Boyle Prof Keith Stanley Prof Shaun Jackson MBBS (HONS) FRACP PHD MBBS (HONS) FRACP PHD MBBS (HONS) BMEDSCI Dr Gregory Stewart Mr Richard Rassi Mr Barry Brownjohn (HONS) PHD Prof Roland Stocker BCOM (UNSW) FCA GAICD BCOMM Prof Richmond Jeremy Mr Tony Stuart Dr Timothy Cartmill MBBS PHD FRACP FAHA BCOM FAICD FAIM FCSANZ GAICD PROFESSIONAL Prof Colin Chesterman AO Mr Richard Utz ADVISERS TO THE MBBS Prof Wendy Jessup BOARD OF GOVERNORS BSC PHD Mr Raymond Vaughan AO Mr John Cloney AM FAIM FAICD FAII Ms Maggie Johns Mr Michael Wallace Honorary Solicitor: Ms Patricia Paton Mrs Giselle Collins Emeritus Prof Geoffrey Ms Clare Walsh BA LLB BEC CA GAICD Kellerman AO Mr Richard Warburton AO (Partner Hamilton Locke) FRACP FRACPA FRAACB Dr Susan Conde LVO Head Auditor: MBBS Prof David Kelly AM Dr Thomas Wenkart Mr Cameron Roan Mr John Conde AO Prof Len Kritharides (Partner KPMG) Prof Judith Whitworth MBBS PHD FRACP Prof Michael Davies FCSANZ FAHA FESC FACC Mr Richard Wylie BSC DPHIL CCHEM FRACI Mr Chris Last Assoc Prof John Yiannikas Mr Craig Davison MMGT GDIP MKTING Mr John Laws CBE OBE Mr Peter Jollie AM GAICD (DECEASED) Ms Joann Lewis Prof Roger Dean BCOM ACA FELLOW FINSIA MA PHD DSC FIBIOL Members of the Institute

FOUNDING FELLOWS

The following members have been recognised with the title of Founding Fellow for their exceptional work in establishing the Heart Research Institute.

Prof Phillip Harris AM BSC MBBS DPHIL FRACP FACC

Mr Ross Hohnen AM OBE (DECEASED)

Prof David Richmond AM MB CHB MSC FRACP FRCP FACC Mr Peter Jollie AM FCA FAICD 14 July 1940 – 8 December 2018

HONORARY FELLOWS On 8 December 2018, the community at the Heart Research Institute lost a true friend who was one of its most loyal and The following members have been dedicated members – Peter Jollie AM FCA FAICD. Peter was recognised with the title Honorary a regular attender of the Annual General Meetings of the HRI Fellow for their outstanding and many of our functions. His advice, drawn from his long service to the Heart Research association with HRI, was always valued. We had been honoured Institute and contributions to have him present at our Illuminate dinner only a month or so as voluntary Governors. The earlier, on 26 October. present Board of Governors is At the HRI Board Meeting of 28 March 1996, the then Chair, indebted to these Fellows for their Dr Bruce Reid, told the Board that Mr Peter Jollie, then President generous philanthropic work and of the Chartered Institute and Managing Director of P&O endowments to the HRI. Containers had agreed to become a member of the Board. Peter Mr Marcus Blackmore AM took up that role at the Board Meeting on 7 May 1996. He was an active contributor to the Board in those relatively early days Mrs Giselle Collins of the Institute and in December 1998 took on the key role of BEC CA GAICD Honorary Treasurer, driving the financial affairs of the Institute Mr Chris Hadley for the following five years. At the same time, he maintained a BA ASIA prominent business life.

Prof Geoffrey Kellerman AO In May 2003, Peter’s daughter, Giselle Collins, joined the Board FRACP FRACPA FRAACB and three months later took over the role of Honorary Treasurer from him. Giselle would go on to play a key role in the building Mr Kevin Kirby AO of Eliza Street and become Chair of the Institute and an (DECEASED) Honorary Fellow. Mr Geoff Lee AM OAM Peter continued to serve on the Board until September 2007, FAO (DECEASED) providing not only his sharp financial acumen and sound strategic Dr Bruce Reid AM sense together with his wide governance experience, but KNO (DECEASED) also taking a special interest in OH&S matters. From his first association with the HRI onwards, Peter worked energetically Dr Carlo Salteri AC and enthusiastically to assist HRI in fulfilling its mission, being (DECEASED) a great champion of the fight against heart disease. It was a privilege to know him and benefit from his wise counsel. HRI has lost a great friend. 62 2018 Heart Research Institute Annual Review

Fundraising Report

DONORS – VITAL FOR THE TREATMENTS OF TOMORROW When I speak with our donors about the exciting breakthroughs our researchers are making, the most common response I receive is “How long will it be until these wonderful discoveries will be available to help people like me?”. It has been said that ‘innovation often moves forward at the speed of cash’. But there are other enablers that can stimulate and facilitate progress: first- class facilities, cutting-edge technology, inspiring leaders, thought-provoking colleagues, world-class collaborators and close proximity to clinicians and their patients. L-R: Prof Shaun Jackson, Dr Lining (Arnold) Ju, At the HRI we are working hard to create the ideal The Hon Brad Hazzard MP environment for innovation and discovery to flourish. The journey from discovery to usage is a long and ILLUMINATE 2018 arduous one. HRI has a number of very promising In 2018, HRI’s annual Awards for Excellence dinner, technologies that have great potential as new Illuminate, celebrated and recognised some of our most therapeutics, devices and diagnostics. However, up-and-coming scientists, as well as the contributions much of this research has not yet reached a sufficient of women to medical research. level of ‘maturity’ to attract professional investors Held at The Women’s College, The University of Sydney, i.e. isn’t ‘investment ready’. the event was attended by distinguished guests and This is where our donors are so vital. supporters from the scientific community, including The When a donor chooses to support the work of HRI, Hon Brad Hazzard, NSW Minister for Health and Minister they choose to accompany our researchers on an for Medical Research. exciting journey to validate their discoveries (often via A highlight of the evening was a Key Note panel more bench research or Phase 1, 2 or 3 clinical trials) comprised of four exceptional women at different stages and ‘accelerate’ their research to a point in the future of their medical research careers: Dr Bo Remenyi, when commercial investment can be sought. paediatric cardiologist and 2018 Australian of the Year All donations (above $2) are 100% tax deductible for Northern Territory; Emeritus Professor Carolyn Geczy, and larger donations might also qualify for ‘matched Acting Scientific Director at HRI; Dr Anna Waterhouse, funding’ via existing Government schemes such as leader of the Cardiovascular Medical Devices Group at the National Health & Medical Research Council HRI; and Emily McCarthy, an honours student from New (NH&MRC) ‘Development Grants’. This is particularly Zealand who first joined HRI on a Summer Scholarship valuable because matched funding grows the impact funded by generous donors in New Zealand. of major donations substantially. Award Recipients Whether you donate as an individual or as a family, a corporate partner, or have remembered HRI in DR LINING (ARNOLD) JU your Will, you can feel deeply satisfied that you are Thrombosis Group accelerating our research towards the treatments Unity4 Best Publication Award of tomorrow. DR YEN CHIN KOAY Thank you. Cardiometabolic Disease Group Dimension Data Early Career Researcher Award

DR RICHARD TAN Applied Materials Group Student Researcher Award

PRADEEP CHOLAN RICHARD WYLIE Vascular Complications Group Director, Fundraising and Brand Student Researcher Award, Highly Commended Fundraising Report

OPTIVER VOTES YES TO BUILDING A PLASMA REACTOR Staff at Optiver Asia Pacific, a leading global electronic market maker based in Sydney’s CBD, voted once again to support the groundbreaking work of HRI’s Applied Materials Group with their Christmas charity donation. Following a talk from Dr Steven Wise and a demonstration of part of the prototype at their charity roadshow, Optiver’s donation this year will contribute to the construction of the world’s first plasma reactor designed specially to produce carbon nanoparticles to deliver treatments for cardiovascular disease. 12 ROUNDS FOR HEART RESEARCH 12 RND Fitness celebrated the launch of their Newtown CLIVE AND VERA RAMACIOTTI FOUNDATIONS gym in April 2018 by donating to a local organisation – SUPPORT THIRD HRI GROUP LEADER HRI. Passionate about getting the community healthy Thank you to the Clive and Vera Ramaciotti Foundations, with their 45-minute trainer-guided circuit-style cardio who awarded a $150,000 Health Investment and strength workouts, 12 RND is a fitting partner for Grant to Dr Anna Waterhouse, leader of the HRI’s HRI, given that one of the best things for the heart is Cardiovascular Medical Devices Group for her work to exercise. Thank you to 12 RND for their generous support. reduce blood-clotting complications caused by devices. This is the third year that the Ramaciotti Foundations CHARITY HOUSIE have invested in an HRI researcher, after they awarded The HRI would like to thank all clubs and venues that Health Investment Grants to Dr Freda Passam in 2017 provide continuing support to ensure the success of the and Associate Professor Sanjay Patel in 2016. Charity Housie Program. Groups involved in this initiative contribute a valuable monetary donation to provide for the program’s overheads and services, as well as raise awareness of HRI within the general community. “How long will it be until these Without their support, the Charity Housie Program would wonderful discoveries will be not be possible. In particular, the Fundraising team would like to extend available to help people like me?” our thanks to the management and staff of: Arena Sports Parramatta Leagues Bankstown RSL Raymond Terrace THANK YOU TO OUR SPONSORS FOR Cabramatta Leagues Bowling club ENSURING THE SUCCESS OF THE 2018 Camden RSL Toukley RSL SYDNEY CARDIOVASCULAR SYMPOSIUM Campbelltown RSL Westport Club Each year, HRI co-hosts the Sydney Cardiovascular Wests Ashfield Symposium with the Victor Chang Cardiac Research Erina Rugby League Institute, bringing together the brightest minds from Ourmbah Lisarow RSL across the state, interstate and internationally to present research, share ideas and form collaborations on the pressing health needs of our time. In 2018, from CHAIRMAN’S BRUNCH December 5–7, the focus was on cardiovascular disease The most recent annual HRI Chairman’s Christmas in the era of obesity and diabetes. Many thanks to the Brunch was held on 8 November 2018. The event sponsors who made the Symposium possible: Diabetes was hosted at the HRI’s Eliza Street headquarters and NSW and ACT, NSW Cardiovascular Research Network, included a tour of the laboratories. This informal event NSW Health, Pfizer, Bayer, Charles Perkins Centre allows the HRI to thank patrons for their generosity, at The University of Sydney, Boehringer Ingelheim, particularly the families and friends of Gift in Will Amgen, Bristol-Myers Squibb (supported through an benefactors. The occasion is an opportunity for the unrestricted education grant), Coherent Scientific, HRI staff and scientists to meet donors in person VisualSonics and Lonza. and discuss how their support is making a difference in the fight against cardiovascular disease. 64 2018 Heart Research Institute Annual Review

HEART RESEARCH INSTITUTE AND The digital component of our regular fundraising appeals DIMENSION DATA TAKE THE STAGE AT throughout the year continued to be successful, with MICROSOFT’S INSPIRE CONFERENCE over $50,000 raised through these appeals as well as HRI were proud to be featured at Microsoft Inspire through donations via our website. 2018 as an organisation that digitally transformed into a modern workplace, enabling us to stay at the leading edge of cardiovascular research. Over 15,000 people attended the conference in Las Vegas, USA in July 2018, where Richard Wylie, HRI’s Director, Fundraising and Brand, took the stage with Dimension Data to talk about how deploying a modern workplace solution has transformed our ability to collaborate, ensure the security of highly sensitive information and attract the best talent.

BEHIND THE SCENES LABORATORY TOURS In 2018, the HRI hosted several ‘Talk and Tours’, providing supporters the opportunity to tour HRI’s facilities and experience the world of research up close, in action. During the tours of our laboratories, guests MAJOR SUPPORTERS learn about HRI discoveries directly from our scientists. Thank you to our major supporters during 2018. This popular event allows the community to witness Barry Timbrell Lin Huddleston first-hand the remarkable research funded thanks to Charles Perkins Centre, The Charitable Foundation their support. University of Sydney Optiver Clive and Vera Ramaciotti Dr Max Hooper Foundations Microsoft 89,352 Diabetes NSW and ACT NSW Cardiovascular GENEROUS DONORS Diane Burger Research Network SUPPORTED HRI IN 2018 Dimension Data NSW Health and Eclipse Environmental Medical Research Sponsorship Program REGULAR GIFTS Edwin Brackenreg Peter and Barbara In 2018, HRI was supported by 89,352 generous Ernest and Piroska Major Hoadley donors, including a high volume of New Zealand and Foundation United Kingdom based contributors. The HRI’s local Qantas Eventide Homes NSW partnerships in these countries continue to grow and Sydney Local Health Helen Elizabeth Pagan Trust enable our mission to globally fight the world’s number District one killer. The HRI appreciates all of our donors, Helen Kirby Unity 4 domestic and international, for their continued support. James N Kirby Foundation Walter and Eileen JJ Richards and Sons Ralston Trust DIGITAL INNOVATION John Fairfax 12 RND Newtown Innovation was the key word for the HRI digital Leon Ball fundraising team in 2018, beginning with a sweeping audit of our web platforms. We isolated and streamlined the services that were giving us a return on investment; anything that drained resources or funds without contributing to growth was sidelined, and everything from Facebook advertising to our Google Ads grant accounts was honed for efficiency. With an eye to diversifying our suite of online fundraising strategies, we launched our first crowdfunding campaign in conjunction with the Applied Materials Group. Using Facebook advertising and email campaign blasts, the six-week campaign raised over $60,000 for the Group and promoted their groundbreaking science to new audiences. With this success, the digital fundraising team plans to conduct further crowdfunding campaigns. Fundraising Report

HEARTS FOR ETERNITY Hearts for Eternity members are special benefactors who have included a gift in their Will to the HRI. These gifts provide the long-term funding needed to achieve scientific breakthroughs. These generous donors are honoured through the Hearts for Eternity memorial sculpture, displayed at the entrance of HRI’s headquarters. The sculpture is an interpretation of the heart and circulatory system, illustrating the inter-relationship of the HRI scientists, staff, and supporters. The benefactor of each gift received is commemorated with a hand-crafted plaque inscribed with their name and displayed on the sculpture for posterity. Any request to remain GIFTS IN WILLS RECEIVED 2018 anonymous will be respected. Estate of Elizabeth Lucas Estate of Eileen Merle Masters HEARTS FOR ETERNITY MEMBERS Estate of Dianne Margaret Snape-Penman Hilda Abbey Mr R Lane Estate of Reginald Llewllyn Stanley Mr John M Adams Mrs Eileen Lange Estate of Dorothy Pickering Ms S Anketell Mr Anthony Lanning- Estate of Brian Gillard Pavey Ms Pat Arnott-Evans Estate of Lola Meryle Bell Mrs Judith Laver Mr & Mrs Gaetano & Leonie Estate of Dorothy Wood Bezzina Mr Thomas Leffers Estate of Edwin Ernest Kajewski Miss M Blums Mrs Donna McGregor Estate of Robert J White Mr L Boyd Ms Rosemary Anonymous (9) Mr David Branscomb McQuade Mr Michael Cavendish Mr I Morrison FUNDRAISING STAFF 2018 Mrs V Chick Mr Michael Michael Farrugia Fundraising Legal and Compliance Manager* Northcombe Ms C Contacos Nick Glenn Digital Communications Specialist Mr I Palmer Mrs E Cornwell Louise Groves Donor Services Representative Mrs Linda Parker Mrs P Falconer Siobhan Hanbury-Aggs Head of Regular Giving Mr & Mrs Judy Mrs Nancy Graeme-Evans Sharon Hodgson Head of Philanthropy (Partnerships Manager)* Pengelly Mrs J Gray Caroline Lels Digital Communications Specialist* Mr J Stone Mrs Vivienne Hall Alessandra Martines Corporate and Trusts and Foundations Manager R H Streifler Mr & Mrs R & L Hammonds Tom Museth Digital Fundraising Manager Mr Ian Strowbridge Mr E Hanna Larnie Narayan Philanthropy Executive* Mr & Mrs K & B Nathan O’Brien Fundraising Business Analyst Mrs Joan Healey Thomasen John O’Shea Pledge Program Manager Ms Margaret Hunter Mrs E Van Der Knaap Laura Petroccitto Gift in Wills Relationship Manager Ms D Janes Melissa Vidler Lisa Petroccitto Single Giving Programs Manager Mr A Jenkins Miss D E Watt Sarah Quan Single Giving Programs Coordinator Mr Gerard Kaudeer Mr Richard Wylie Rosemary Warwick Donor Services Coordinator Mr & Mrs R & M Kippax Anonymous (99) Susan Barbara Klimpsch Richard Wylie Director, Fundraising and Brand Helena Yiu Database and Transactions Executive Valentin Ziegler International Fundraising Manager Michel Zwecker Head of Philanthropy

MARKETING AND COMMUNICATIONS STAFF Sarah Hawkesford Marketing Executive* Betty Loi Content Manager Hester Stuart Marketing and Communications Manager

*Left in 2018 66 2018 Heart Research Institute Annual Review

Operations Report

The purpose of the Heart Research INFORMATION TECHNOLOGY Information security was a focus of the information technology Institute Operations Team is to industry in 2018 and has likewise been a high priority for HRI. provide first-class support to our This year, the IT team completed significant information security infrastructure upgrades, including email, firewall and endpoint scientists, and to ensure all teams protections, bringing next generation security architecture to have the equipment and services the Institute. required to drive their research The HRI continues to invest in the flexibilities and efficiencies offered by the cloud. IT is improving our use of cloud technologies forward with minimal hindrances. to integrate further our two research sites and ensure equitable access across these locations. The HRI strengthened partnerships with Microsoft’s Tech for Social Impact division in 2018, and in conjunction with Dimension Data, won Microsoft’s Global Modern Workplace Transformation FINANCE Award. IT continues to leverage the latest scientific and workplace INCOME software, equipping our scientists to collaborate internally, among The revenue HRI received from Australia and overseas for local organisations, and globally with other researchers. Digital 2018 was $25.4 million (FYR17: $25.8 million). Fundraising technologies continue to transform our practices from research and bequest income grew in 2018. through to operations, and IT looks forward to new opportunities in 2019. Other income of $315,000 in 2018 was 85% higher when compared to the prior year. This was principally due to the income derived from the renting out of floor space in the Eliza Street, Newtown, Sydney building. EXPENDITURE Operating expenditure of $26.2 million during the year was 7.35% lower when compared to the costs incurred in 2017. Fundraising costs of $8.9 million were $2.9 million, or 24%, lower than in 2017. OPERATING RESULT The Institute’s results from operating activities plus net investment income and other comprehensive income was a total comprehensive loss of $156,000. This result was $826,000 better when compared to the results in 2017. FINANCIAL POSITION The net asset position of HRI as at 31 December 2018 was $40.3 million. This consisted of $15.5 million in current assets, $13.7 million in investments, $16.1 million in net fixed assets and $4.97 million in total liabilities. Cash and short-term investments of $13.9 million, together with managed investments funds of $13.7 million, place HRI in a strong position to continue its battle against cardiovascular disease in the years to come. A copy of our full annual financial report is available from our website or by contacting the Heart Research Institute at [email protected] Operations Report

OPERATIONS AND SCIENTIFIC STAFF

JASHMI BASTOLA Biological Facilities Attendant VANIA DAUNER Executive Assistant ELISSA DWYER HUMAN RESOURCES Director, Human Resources The HRI has continued to attract top talent through the Sydney MEGAN FRASER Cardiovascular Research Fellowship program, in partnership Research Grants and Contracts Manager with The University of Sydney. We have also continued to focus on developing our existing staff through access to LinkedIn LEI HONG Financial Accountant* Learning for self-directed learning, participation in the Franklin Women mentoring program, access to leadership training for CARMEL GANGEMI all managers, and a greater focus on health and wellbeing Receptionist/Administrator with training conducted by our Employee Assistance Program JORDANA GOTH provider. The HRI Diversity Council co-ordinated an excellent Scientific and Facilities Support Technician International Women’s Day event, and HRI participated for the KATJA HUMPHRYS first time in the Workplace Gender Equality Agency review. Animal Technician In 2018, the HRI New Zealand Summer Scholarship program ROB JONES ran for its third successful year, with a record number of 10 Human Resources Advisor students attending over the 2018/2019 summer break. Ensuring we remain competitive on salary and benefits has continued to MORGAN JONES Scientific and Facilities Support Technician be a key focus for Human Resources, with participation in the inaugural Aon Hewitt salary benchmarking survey for medical BELLE KONG research institutes and an ongoing review of our salary scales Research Grants and Contracts Manager* as compared to relevant Sydney-based universities. JASMINE LAM Senior Accountant SCOTT MARTIN Head of Finance PHILIP MORGAN WHS and Laboratory Manager “Cash and short-term MICHELLE MORGAN-MAR investments of $13.9 Receptionist/Administrator* ERIN O’BRIEN million, together with Receptionist/Administrator managed investments LINDA PETERSON BROWN funds of $13.7 million, Human Resources Advisor TIM PINNOCK place HRI in a strong Head of IT position to continue PAT PISANSARAKIT Senior Research Assistant – its battle against Tissue Culture and Histology* cardiovascular disease TYM RICHARDSON in the years to come.” Facilities Manager SATHY SAPPANY Head of Finance* SNEZANA STOJANOVSKA Accounts Payable Officer GORAN TKALCEC IT Administrator JESSICA TOOLAN Biological Facilities Manager

*Left in 2018 68 2018 Heart Research Institute Annual Review

Thank you, from the bottom of our hearts

No matter what role you play, either within HRI or as an external collaborator or supporter, you are pivotal to the quest to reduce the number of people suffering from cardiovascular disease.

Together, we can fight the second coming of cardiovascular disease. Thank you

It takes a heart of gold to end heart disease.

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