Bringing Research to Life

ANNUAL REPORT 2013 ART OF THE HEART 2013 Annual Report 2013 From humble cell beginnings come hearty complexities – winning entry from Alexis Bosman, Developmental & Stem Cell Biology Division This heart shaped cluster of cells 400x magnified was created using induced pluripotent stem cells, a specialised type of stem cell which originally began as skin cells. After ‘reprogramming’, the cells have the ability to form any cell type of the body, including cells of the heart. Under special conditions, these cells can be coaxed into producing heart muscle cells (cardiomyocytes).

VICTOR CHANG CARDIAC RESEARCH INSTITUTE Bringing research to life THE VICTOR CHANG CARDIAC RESEARCH INSTITUTE Lowy Packer Building 405 Liverpool Street Darlinghurst, NSW, Australia 2010 Phone: (02) 9295 8600 – 1300 842 867 International Phone: +61 2 9295 8600 Fax: (02) 9295 8601 International Fax: +61 2 9295 8601 www.victorchang.edu.au ABN 61 068 363 235

CONTENTS

Mission...... 2

Trustee’s Foreword...... 4

Organisational Structure 2013...... 5

About Us...... 6

Dr Victor Chang...... 7

Chairman’s Report...... 8

Executive Director’s Report...... 10

Board of Directors...... 12

Our Committees...... 15

Research Divisions Overview...... 17

Cardiac Physiology & Transplantation Division...... 18 Science in the Spotlight: Macdonald Laboratory...... 23 Developmental & Stem Cell Biology Division...... 24 Science in the Spotlight: Harvey Laboratory...... 26 Molecular Cardiology & Biophysics Division...... 28 Science in the Spotlight: Fatkin & Vandenberg Laboratories...... 30 Molecular, Structural & Computational Biology Division...... 32 Science in the Spotlight: Suter Laboratory...... 34 Vascular Biology Division...... 36 Vascular Biology comes to the Chang...... 37

Awards & Achievements 2013...... 38

Paul Korner Seminar Series...... 40

Barbara Ell Seminar Series...... 41

Publications 2013...... 42

Financial Summary...... 45

Fundraising 2013...... 46

Community Outreach 2013...... 50

Art of the Heart ...... 52

Corporate Supporters...... 54

ANNUAL REPORT 2013 3 Trustee’s Foreword

The Trustees are privileged to meet many dedicated and committed people as we visit the facilities Mary Aikenhead Ministries was among the health, health research, education and welfare works initiated by Sisters of Charity. established by the Holy See as This year particularly as we celebrate the 175th anniversary of the arrival in Sydney of the first a Public Juridical Person at the five Sisters from Ireland. request of the Congregation of the Religious Sisters of Charity The Sisters recognised the importance of research as fundamental to better health outcomes and this of Australia to succeed to, a vital component of the Sisters’, and now our, commitment of service of the poor and marginalised and to carry on and expand, in our community. The additional legacy of the skills and passionate care of Dr Victor Chang is various health and aged continued through this Institute by the research undertaken and the translation of research into care, education and welfare high quality care and outcomes. ministries conducted by the The Trustees take this opportunity of expressing our immense gratitude to Mr Steven Lowy AM Sisters of Charity. for his almost twenty years of service to the Institute as Board member and Chairman. His contribution The Victor Chang Cardiac as leader is immeasurable. We welcome the new Chairman Mr Matthew Grounds. We also thank Research Institute Limited is Professor Bob Graham, the Board, staff and supporters for your continuing contribution and success. a Research Ministry within On behalf of the Trustees of Mary Aikenhead Ministries, I am pleased to commend to you the Mary Aikenhead Ministries, 2013 Annual Report of Victor Chang Cardiac Research Institute. which operates in accordance with the Canonical Statutes

approved by the Holy See in Rome. Mary Aikenhead Ministries also assumes an Australian civil identity under David Robinson Australian law as the Trustees Chairman, of Mary Aikenhead Ministries. Trustees of Mary Aikenhead Ministries The Trustees operate pursuant to the Constitution of Trustees of Mary Aikenhead Ministries. In 2013, the Trustees are Mr David Robinson, Sr Helen Clarke, Professor Gabrielle McMullen, Ms Rowena McNally, Dr Tessa Ho and Mr Jim Russell.

4 Victor Chang Cardiac Research Institute ORGANISATIONAL STRUCTURE Mary Aikenhead Ministries 2013 Chair, Mr David Robinson

Affiliations University of NSW Board Committees St Vincent’s Health Australia Finance Chair, Mr David Craig Appeals Chair, Mrs Louise Di Francesco St Vincent’s Research Precinct Garvan Institute of Medical Research Media and Communications Board of Directors Chair, Ms Jill Margo AM St Vincent’s Centre for Applied Chairman, Mr Steven Lowy AM Medical Research

Executive Director Scientific Advisory Committee Professor Robert Graham AO Deputy Directors Professor Richard Harvey Professor Jamie Vandenberg

Chief Operating Officer Molecular Cardiology and Biophysics Ms Dianne Kitcher (to September) Division Head, Ms Janina Jancu (from November) Professor Robert Graham AO

Developmental and Fund Development Stem Cell Biology Ms Jan Savage Division Head, Professor Richard Harvey Administration Finance Human Resources Cardiac Physiology and Information Technology Transplantation Policy Division Head, Professor Michael Feneley AM Media and Communications

Essential Services Core Facilities Molecular, Structural and Computational Biology Division Head, Dr Daniela Stock

Vascular Biology Division Head, Professor Roland Stocker

ANNUAL REPORT 2013 5 About Us

WHO WE ARE OUR INSPIRATION INDEPENDENCE In his memory, the five research Founded in 1994, originally A pioneering surgeon, Through contributions from divisions and 17 under the auspices of the researcher and humanitarian, the NSW and Australian laboratories of the Sisters of Charity and St Dr Victor Chang AC founded Federal Governments, the Institute work with a Vincent’s Hospital, the the National Heart Transplant Lowy and Packer families, single vision – to reduce Victor Chang Cardiac Program at St Vincent’s the Atlantic Philanthropies, the incidence, severity and Research Institute became an Hospital in 1984, and in 1990 the National Australia Bank, impact of heart diseases, independent research facility spearheaded the Heart of ANZ Bank, Citigroup and particularly those causing heart in 1995. It is committed to St Vincent’s Appeal. many others, the $80 million muscle diseases, which directly excellence in research, training Lowy Packer Building was This Appeal raised much- affect the heart’s ability to and the rapid translation constructed and formally needed funds for a Cardiac pump sufficient blood for the of discoveries into new opened by Her Royal Transplant Ward and Cardiac body’s needs and can result diagnositic, preventative Highness Crown Princess Diagnostic Unit at St Vincent’s in the most severe forms of and therapeutic regimens Mary of Denmark on – and created the impetus for heart failure. for people with or at risk of September 3, 2008. establishing the Victor Chang heart disease. The Institute is These research programs Cardiac Research Institute after dedicated to the memory of address vital contemporary his untimely death in 1991. WORKING FOR A cardiac surgeon Victor Chang BETTER FUTURE issues – including heart and his passionate belief in the development and congenital In Australia, more than 45,000 power of discovery. ESTABLISHMENT heart disease, inherited The new Institute was opened people die of cardiovascular heart diseases, the potential Our team of over 150 full-time on 14th February 1994, thanks disease each year. It kills one application of adult stem cell staff work across five research to generous donations from Australian every 12 minutes. technologies in cardiovascular divisions – Cardiac Physiology the late Mr Kerry Packer, AC, Heart failure also remains care, cardiac arrhythmias, and and Transplantation, the Federal Government, and the most common cause of how heart function is regulated Developmental and Stem Cell the Australian public. The hospital admissions for people in response to stresses like high Biology, Molecular Cardiology Institute was incorporated aged over 65, although it can blood pressure and ageing. and Biophysics, Molecular, as an independent research affect anyone regardless of Structural and Computational facility on 27th February age or gender. Through heart Biology, and Vascular Biology. 1995. In 1996, the Institute’s surgery, Dr Victor Chang was temporary premises in the able to save hundreds of lives, Garvan Building were opened but he knew that research by the late Diana, Princess of could save thousands. Wales.

In Australia, more than 45,000 people die of cardiovascular disease each year - one every 12 minutes.

6 Victor Chang Cardiac Research Institute Our Inspiration: Dr Victor Chang VICTOR CHANG, AC (1936 – 1991)

A highly accomplished surgeon, humanitarian and skilled campaigner, Dr Victor Chang was a pioneer in the modern era of heart transplantation. His achievements include the saw the incredible value of Travelling overseas to extend At the same time, he helped development of Australia’s research – playing a key role in his skills, Dr Chang attained a teams from St Vincent’s travel National Heart Transplant the development of an artificial Fellowship in Surgery from the to China, Singapore and Program at St Vincent’s heart valve and, in later years, English and American College Indonesia where they shared Hospital, which has performed an artificial heart assist device. of Surgeons and returned to their medical, surgical, nursing, thousands of successful heart, St Vincent’s Hospital in 1972, hospital administration and Victor Chang (Yam Him) was heart-lung, and single lung where he worked with the audiovisual expertise. born in Shanghai to Australian- transplants since 1984. He also renowned Dr Harry Windsor born Chinese parents in 1936. In 1986 Dr Chang was and Dr Mark Shanahan, who He came to Australia in 1953 awarded Australia’s highest had performed Australia’s first as a student at the Christian recognition, a Companion of heart transplant at St Vincent’s Brothers College, Lewisham. the Order of Australia (AC), Hospital in 1968. In 1962 he graduated from while the University of New Sydney University with a During the 1980’s Dr Chang South Wales awarded him Bachelor of Medicine, Bachelor lectured extensively in China, its highest degree of MD of Surgery, becoming an Hong Kong, Indonesia, (Honoris Causa) for “scholarly intern and, later, a registrar Singapore and Malaysia. He achievement and humanitarian in cardiothoracic surgery at also founded the Australasian- endeavour”. St Vincent’s Hospital. China Medical Education Victor Chang died in tragic and Scientific Research circumstances in Sydney on Foundation, which sponsored 4 July 1991. South-East Asian doctors, nurses and students to work in He was an honorary Professor Australia to develop improved of Surgery to the Chinese skills and quality-of-care to Academy of Medical Science in take back to their home Peking; an honorary Professor countries. of Surgery to Shanghai Medical School; official adviser on cardiac surgery development in Indonesia; and a member of the Australia China Council. In 2000, Dr Victor Chang was named Australian of the Century by the people of Australia.

In 2000, Dr Victor Chang AC was named Australian of the Century by the people of Australia.

ANNUAL REPORT 2013 7 Chairman’s Report

Dr Victor Chang was a truly remarkable Australian, a pioneering cardiothoracic surgeon and humanitarian with a passionate belief in the power of discovery. Victor knew that through surgery, hundreds of lives would be saved, but that medical research would save many thousands more.

It is this belief that has It has meant we live longer In this context, the Institute is In 2013, the Institute published sustained and inspired the and more fulfilling lives. It has an outstanding example of an an impressive 80 papers, nine work of all involved with reduced the burden of misery investment in the intellectual editorials, six reviews and two the Victor Chang Cardiac and disease and early death for foundation of our city. book chapters. These spanned Research Institute since it was millions around the world. some of the world’s leading Thousands of people and established in 1994 to honour medical journals, including But we have become many companies have helped Victor Chang’s memory and Nature, Circulation and the conditioned to this progress. make that investment, continue his work. Lancet. including the loyal supporters We take it for granted, as This is my final report as who attend our events and You can read in more detail though it occurs naturally and Chairman, having decided to help promote our work in the about the year’s scientific that progress will somehow retire after nearly 20 years’ community. highlights, including the continue to be made. service on the board, seven pioneering work of the I am pleased to report that my as Chairman, and it presents As our researchers at the Macdonald Laboratory in the final year as Chairman was an opportunity to reflect on Institute know all too well, it field of heart transplantation, another successful year for the role of the Institute in doesn’t work like that. within the ‘Science in the the Institute and in this report our society. Spotlight’ sections of this Progress comes from you’ll find many excellent report. I believe the Institute has painstaking work, week after examples of groundbreaking made, and continues to make, week, year after year, until research into cardiovascular Prudent management of our an enormous contribution not finally a breakthrough is made. disease, a condition that claims budget and success in grant just to our current lives and the lives of more than 40,000 outcomes and fundraising It’s a constant challenge to to the life of Sydney, but to Australians each year and is has maintained the Institute’s remind ourselves that the huge the ongoing story of human our nation’s biggest killer. sound financial position. For advances are made with tiny development. 2013, the Institute budgeted steps, and each tiny step has to The task at hand for our for a deficit of $2.0 million, That sounds like a grand be supported, and encouraged scientists, to reduce the but I am pleased to report a statement, but it’s true. and funded. And that is what impact, severity and suffering strong result with a surplus of the Institute and its many caused by heart disease, Throughout history, and $1.3 million, being $3.3 million supporters have done so well remains as urgent and especially over the past better than budgeted. over the years. important as ever. 100 years or so, the human In 2012, the unrealised gain race has taken great strides While I’m proud of the Throughout the past year, on revaluation of financial forward in all areas of human achievements of the Institute the Institute has continued to assets was $983,000, which endeavour, and especially in in advancing the cause of contribute significantly to the improved further in 2013 to an the field of medical research. medical science, I’m also proud knowledge of the international unrealised gain of $1.5 million. of the role it plays in our city. scientific community, and we The impact has been immense. This was due to a better can be proud that this year we I have long believed that what performance of the financial have recruited, and continue to makes a city great is what its markets, and stringent support, some of the brightest citizens themselves create and management by the Finance minds in scientific research. not what is bequeathed by Committee. nature. Direct research grant income increased by $1.6m, from Progress comes from $8.4million in 2012 to $10million in 2013. painstaking work, week Fundraising activities generated $6.0 million in revenue during the year, after week, year after year, including $2.0 million from until finally a break- bequests. through is made.

8 Victor Chang Cardiac Research Institute Fundraising continues to be an Thanks also to Professor Les He has been the driving force I welcome my successor, Mr essential element in bridging Field who continued to provide of the core business of the Matthew Grounds, who is an the gap between grant income valuable input, particularly in Institute – our research – outstanding individual and and our operating costs. It terms of academic issues, in and he thoroughly deserves who, together with the board, plays an important role in his capacity as Deputy Vice the respect and admiration Bob Graham and the research extending our network of Chancellor (Research) at the he enjoys throughout the team, will lead the Institute supporters, and raising our University of New South medical research community into its next phase of growth profile in the wider community. Wales. internationally. and success. 2013 saw some terrific I would also like to thank Bob’s team, again too Finally, thank you to everyone fundraising and community the Trustees of the Mary numerous to mention who has been associated with outreach initiatives and these Aikenhead Ministries, board individually, are an outstanding the Victor Chang Cardiac are outlined in more detail in member, Sr Anthea Groves, group of individuals and it has Research Institute during my this report. Appeals Committee Member, been a humbling experience involvement. It has been very Sr Clare Nolan, and all of the for me to have helped them personally rewarding and I However gaining grants for Sisters of Charity. continue their important work. am proud to have been able future years has been more to play a role, along with so challenging in terms of peer- Most of the individuals I have I am sad that my formal ties many others, in its success. reviewed grant income. just mentioned have become with the Institute will end with close friends through our this report, but I do so in the We received $5.5 million in work together at the Institute knowledge that I will remain a new grant and fellowship and there have been many lifelong friend of the Institute funding, which along with others, both board members and maintain an interest in its Steven Lowy AM essential donations from the and Institute staff, past and progress. Chairman public, is used to directly fund present, too numerous to our research work. mention here. This included $2.08 million But in this, my final report, I from the National Health & would like to acknowledge the Medical Research Council enormous contribution made (NHMRC), $785,000 from the by the Packer family. Kerry Australian Research Council Packer was instrumental in (ARC), and $2.6 million from establishing the Institute. His the National Heart Foundation wife Ros served on the board and other foundations and for many years and their son trusts. James has continued that In my final year I continued support and close involvement. to benefit from the support The enormous financial of my fellow Board members, contribution of Atlantic including Mr David Craig, Philanthropies via Mr Chuck who chairs the board’s Finance Feeney is also gratefully Committee; Mrs Louise Di acknowledged. Chuck’s very Francesco, who chairs the generous contribution was Appeals Committee, and Ms critical for our move into the Jill Margo, who chairs the new building, as well as for Media and Communications ongoing research. Committee. I would also like to recognise We welcomed Professor my predecessor, the Terry Campbell, Head of the Honourable Neville Wran. Department of Medicine Neville was an inspired leader at St Vincent’s Hospital to of the Institute and we could our Board of Directors, and not have wished for a more farewelled Mr Ryan Stokes. ideal founding Chairman. Ryan made a major impact in expanding the reach of the Nor could we have had a Institute to Western Australia more ideal founding Executive and we are very grateful to Director than Professor Bob him for providing us with Graham. his considerable corporate experience and expertise. ANNUAL REPORT 2013 9 Executive Director’s Report

Discovery begins with individuals, and at the Victor Chang Cardiac Research Institute, we recognise those individuals and create extraordinary teams.

Our teams are making At an international conference In the absence of the gene, One of the Institute’s most discoveries that will shape the on organ donation held in they showed that the large affable characters and Head future of human health and, Sydney, the team announced vessels leading out of the of our Mechanobiology building on Victor Chang’s they have found a way to heart, including the aorta, Laboratory, Professor Boris powerful vision, will reach protect hearts that have which supplies the entire body Martinac, was elected to the beyond the laboratory to stopped beating, in what is with oxygenated blood, did Fellowship of the Australian benefit all Australians. known as circulatory death, not form properly. Academy of Science. This is and bring them ‘back to truly one of the highest levels Although we understand This year, Richard also received life’ outside the body, for of recognition of academic more now than ever before the Ministerial Award for subsequent use as donor achievement and excellence about cardiovascular disease, Cardiovascular Research organs for people needing a and is thoroughly deserved, it remains the nation’s leading Excellence from the Hon. Jillian heart transplant. given Boris’s pioneering work cause of death and so our Skinner, an accolade he richly leading to the discovery vitally important mission As many will know, there are deserves as one of Australia’s of mechanosensitive ion continues unabated. simply not enough hearts most talented scientists. channels. available for all those who In 2013, a number of our Research into how our genes need one, and a significant Another faculty member who teams made important ‘behave’, and how heart number of people die on the had an outstanding year in breakthroughs. disease is developed and donor waiting list each year. 2013 was Diane Fatkin, who passed through generations, Firstly, Professor Peter This exciting work could was promoted to Professor will help us develop Macdonald’s Laboratory prove pivotal in increasing the of Medicine by the University preventative treatments that continued their outstanding desperate shortage of donor of New South Wales, and can break the cycle of an work in the field of heart hearts by 15 – 20 per cent, awarded the Royal Australasian inherited family health legacy. transplantation. possibly more. College of Physician’s Associate Professor Cath Suter ‘Eric Susman’ prize for her Professor Richard Harvey’s and her team, publishing outstanding contributions team also made a major in the journal Epigenetics, to internal medicine. finding in the field of demonstrated that while Developmental Biology, obesity and type 2 diabetes in showing, for the first time, mothers can program children the importance of a single to develop metabolic conditions gene, Nkx2-5, in forming the later in life, this can be large vessels of the heart. overturned if the children are careful about what they eat.

Although we understand more now than ever before about cardiovascular disease, it remains the nation’s leading cause of death, and so our vitally important mission continues unabated.

10 Victor Chang Cardiac Research Institute We also warmly welcomed Steven’s leadership has also Dr Joshua Ho this year, helped us to develop an who joined the Institute international reputation for after completing his PhD excellence in cardiovascular in bioinformatics at Sydney research and training. Quite University and then undertook simply, his contributions have very successful postdoctoral been outstanding. studies at Harvard Medical I would like to thank our staff, School. At just 28, Joshua is and our Friends, for your our youngest faculty member ongoing contribution and who is already providing commitment to the Institute. important leadership and Thanks to your efforts, 2013 enhanced capacity in the was another successful year increasingly important in our fight against discipline of bioinformatics. cardiovascular disease. Our scientific research is Finally, I would like to supported by our exceptional acknowledge the leadership Board, and their passionate of The Mary Aikenhead belief in the work we do. Ministries, so ably Chaired I would like to take this by David Robinson, and opportunity to thank Mr importantly the Sisters of Steven Lowy, who is standing Charity, who continued to down after almost twenty inspire us—31 December 2013 years on the board, including marking their 175th year of the last seven as Chairman. vital health and education service to the people of Steven’s contributions to Australia. the Institute have been immeasurable, both financially We now look forward to and in terms of his time and the year ahead with energy, expertise. enthusiasm and vigour, as we continue to honour Victor He was instrumental in helping Chang’s great legacy. us to deliver the world-class research facility we now call home, and has helped us to build a Board of colossal stature and experience.

Professor Robert M. Graham AO Executive Director

ANNUAL REPORT 2013 11 Board of Directors

The successful operations of the Victor Chang Cardiac Research Institute are heavily reliant on the loyalty, drive and vision provided by the Board of Directors, led by Mr Steven Lowy AM, and subsidiary committees.

Mr Steven Lowy Professor Robert M Graham Professor Terry Campbell Mr David Craig AM, BCom (Hons) (Chairman) AO, FAA, MBBS (Hons), MD, AM, MD, DPhil, FRACP BEc, FCA, CTFP FRACP, FACP, FAHA Mr Lowy joined the Victor Professor Campbell joined Mr Craig joined the Victor Chang Board as an inaugural Professor Graham is Executive the Victor Chang Board in Chang Board in 2007 and took member in 1995 and became Director of the Victor Chang 2013. He is the Head of the over as Chair of the Institute’s Chairman in 2008. He Cardiac Research Institute, Department of Medicine at St Finance Committee in 2012. currently serves as Co-Chief and a member of its Finance, Vincent’s Hospital, and Deputy Since 2006 he has been the Executive Officer of the Appeals, Intellectual Property Dean of Medicine, University Chief Financial Officer of Westfield Group. Mr Lowy and Commercialisation and of NSW. From 2003 to 2009, the Commonwealth Bank of holds a Bachelor of Commerce Media and Communications he served as Deputy Director Australia. Mr Craig has over 30 (Honours) degree from the Committees. He is the Des of the Institute alongside years of experience in financial University of NSW. Prior to Renford Professor of Medicine, Professor Richard Harvey. He management, strategy, joining Westfield in 1987, and Professor of Biotechnology also served as President of the mergers and acquisitions. he worked in investment and Biomolecular Science, Cardiac Society of Australia His previous roles included: banking in the United States. University of NSW, and and New Zealand from 2000 Chief Financial Officer for Mr Lowy is President of the Professor (adjunct) of to 2002. Australand; Global Transition Board of Trustees of the Art Physiology and Biophysics, Finance Leader for IBM Professor Campbell’s research Gallery of New South Wales. Case Western Reserve Business Consulting Service; work has encompassed both He is a director of the Lowy University School of Medicine, Global Chief Financial Officer basic laboratory research Institute for International Cleveland, Ohio. He is a of PwC Consulting, and Chief and clinical cardiology. He Policy, and a member of the Fellow, Australian Academy Operations Officer and for has published over 100 Prime Minister’s Business- of Science (AAS) and foreign 15 years Senior Audit Partner peer-reviewed papers in Government Advisory Group member, Royal Danish of PricewaterhouseCoopers international journals, and on National Security. Mr Lowy Academy of Sciences and Australasia. has held competitive research is a Life Governor of the Victor Letters. He is a member of funding from both the Mr Craig is a director of the Chang Cardiac Research the American Association National Health & Medical Financial Executives Institute of Institute. In addition to his for Clinical Research, the Research Council and National Australia and has also served role as Chairman of the Board, American Society of Clinical Heart Foundation. as a director of Australian Gas he is a member of its Finance Investigation and the American Light Company. Committee. Heart Association, and a Life In 2003, he was appointed Member, Heart Foundation as a Member of the Order of Australia. of Australia (AM).

Dedication, commitment, vision.

12 Victor Chang Cardiac Research Institute She is a specialist in all New Zealand. Before joining areas of corporate media Australian News Channel, he management, public relations, held positions at British Sky issues management and crisis Broadcasting, the Nine Network management, and has worked and Prime Television. Mr on campaigns for AAPT, CeBIT, Frangopoulos is the Chairman Mercedes Australian Fashion of the Australia Day Council of Week, Alterian, Carbon Planet, NSW, a member of the Charles Australand, Lend Lease, Sturt University Council, a Multiplex, Colliers, Landcom member of the Advisory Board and James Fairfax. Mrs Di of Macquarie University’s Centre Francesco is a board member for Media History, and a Director Mr Chum Darvall Professor Leslie Field of National not-for-profit of the Australian Subscription BA, F Fin, FAICD AM, FAA, DSc, PhD, BSc organisation, Fitted for Work. Television and Radio Association Mr Darvall joined the Victor Professor Field joined the and a Board Member of the Chang Board in 2008, and Victor Chang Board in Walkley Foundation. is a member of its Finance 2009. He was appointed Committee. He was Chief to his current position as Executive Officer, Deutsche Vice-President and Deputy Bank Australia and New Vice-Chancellor (Research) Zealand, from July 2002 to at the University of NSW March 2011. He is now non- in 2005. His main areas of executive Vice Chairman of research are organometallic Deutsche Bank. Prior to this chemistry, catalysis and NMR he worked in a variety of roles spectroscopy. He is the author across the banking industry Mrs Barbara Ell of more than 200 scientific including: Director of Treasury papers and 4 text books. He and Head of Global Markets Mrs Ell has been a Victor is the recipient of the Rennie Mr Matthew Grounds at Deutsche Bank and positions Chang Board member since Medal (1983); The Edgeworth BCom, LLB (Hons) in the financial markets division 2001 and is a Life Governor David Medal (1986); The of Westpac. Mr Darvall’s of the Institute. She is a Organic Chemistry Medal Matthew is currently Chief current Board memberships member of the Institute’s (1992); the Centenary of Executive Officer of UBS include: TransGrid, Wilson Appeals Committee and is Federation Medal (2003) and Australasia (since May 2008) HTM, Pinnacle Investment the Chair of the Victor Chang the RACI Leighton Medal and Head of Corporate Client Management Ltd, Metrics Day Organising Committee. (2010). He was elected as Solutions, Asia Pacific. Prior Credit Partners Pty Ltd, Mrs Ell was born in Auckland, a Fellow of the Australian to being appointed as Head Palisade Investment Partners New Zealand and educated Academy of Science (AAS) of Corporate Client Solutions Limited, the Financial Markets at St Mary’s College prior in 1996 and appointed as in November 2012, Matthew Foundation for Children, to her nursing training at a Member of the Order of held the position of Joint Global Macquarie University Council, Auckland Hospital. She then Australia in 2011 for his Head of Investment Banking. Major Performing Arts Panel continued her nursing career services to Chemistry and to Matthew is a member of the Australia Council and at Merriwa District Hospital. Higher Education. In 2013, of the UBS Asia Pacific the Australian Cricketers’ After marrying, Barbara moved he was appointed Secretary Management Committee, Association Player Hardship to Sydney, where she raised for Science Policy with the the UBS Investment Bank Fund. her three children, Justine, AAS and is a member of the Global Executive Committee Sara and Robert. In addition Council of the AAS. and a Group Managing to serving on the Victor Chang Director. With more than 20 Appeals Committee, Barbara years investment banking is widely recognised for her experience, Matthew is leadership in philanthropy and one of Australia’s leading charity work. corporate advisers and has been responsible for a number of landmark transactions for major Australian and international companies. Matthew is also a member of Mrs Louise Di Francesco the University of New South Mr Angelos Frangopoulos Mrs Di Francesco joined Wales Council, a Director BA(Comm), MAICD, JP the Victor Chang Board in of the Australian Business 2010 and is the Chair of its Mr Frangopoulos joined the and Community Network Appeals Committee. Mrs Victor Chang Board in 2009 and Council and Director of the Di Francesco has worked is a member of its Media and UBS Foundation. Matthew in the media industry for Communications Committee. graduated from the University more than 30 years, initially He is the CEO of Australian of New South Wales and as a journalist, and for the News Channel Pty Ltd, the holds a degree in Commerce past 22 years, in media and owner and operator of Sky (Finance Major) and Law. corporate communications. News Australia and Sky News

ANNUAL REPORT 2013 13 Board of Directors

various businesses involved in marketing, finance, trade, primary production, property and healthcare. In addition to serving as a director of the Victor Chang Institute, he was an inaugural member of its Appeals Committee.

Sr Anthea Groves Mr Ryan Stokes Dr Gary Weiss RSC, OAM, RN LHA Dip. of BCom LLB (Hons), LLM, JSD Nursing Administration Mr Stokes joined the Victor Dr Weiss joined the Victor Sr Anthea Groves has been a Chang Board in 2011. He is Chang Board in 2009 and member of the Victor Chang CEO of Australian Capital is a member of its Finance Board since 2003. She is a Equity Ltd (ACE) and Chief Committee. He holds the member of the congregation Operating Officer of Seven degrees of LLB (Hons) and of the Sisters of Charity and Ms Jill Margo Group Holdings (SGH). Mr LLM (with dist.), as well as is Patient Liaison Officer at AM, BA (Hons) Stokes is also a Director of a Doctor of Juridical Science St Vincent’s Hospital Sydney. WesTrac, Seven West Media (JSD) degree from Cornell Sr Anthea is a Director of the Ms Margo joined the Victor and Iron Ore Holdings. He is University, New York. Dr Weiss Sisters of Charity Foundation. Chang Board in 2008 and is the Chairman of The National is Chairman of Clearview the Chair of the Institute’s Library of Australia and a Wealth Ltd and Secure Parking Media and Communications Director of the Australian Pty Ltd, an Executive Director Committee. She is the health Strategic Policy Institute of Ariadne Australia Limited editor of The Australian Council. and a Director of several Financial Review. She has other organisations, including won numerous international Premier Investments Limited, and national media awards, Ridley Corporation Ltd, including two Walkleys and a Pro-Pac Packaging Ltd and Churchill Fellowship. In 2006, The Centre for Independent Ms Margo was awarded an Studies. Order of Australia for services to journalism and cancer. She holds a BA (Hons) in English Mr John Kean literature, and is a best-selling OAM, FCA, FAICD author and biographer. Mr Kean has been a member of the Victor Chang Board since 2003, is a Life Member of the Institute and was the Chair of the Institute’s Finance Committee until retiring from this position in 2012. He is Executive Chairman of Pinpoint Pty Limited. He also acts as an Independent Business Advisor and holds directorships in

14 Victor Chang Cardiac Research Institute Our Committees

APPEALS COMMITTEE VICTOR CHANG DAY ORGANISING The Appeals Committee consists of a group of volunteers and COMMITTEE staff who are responsible for the Institute’s fundraising events, This committee is responsible for organising the Institute’s major aimed at raising the vital funds needed by the Institute to annual fundraising event, the Victor Chang Day Gala Ball. conduct its groundbreaking research. Members Members Mrs Barbara Ell (Chair), Mrs Ann Chang, Mr Cameron Irving, Mrs Louise Di Francesco (Chair), Mrs Ann Chang, Mr Marcus Mr Ken Laing, Ms Emma Quick, Mrs Michele Parker, Mrs Diana Chang, Mr Alan Crouch, Mrs Barbara Ell, Mr Errol Goldberg, Ritchie, Ms Ruth Zukerman, Professor Robert Graham, Ms Jan Professor Robert Graham, Mr Cameron Irving, Sr Clare Nolan, Mrs Savage, Ms Eliana De Sousa. Antoinette Ogilvie, Mr Michael Renford, Mr Robert Ryan, Ms Jan Savage, Mr Alex Schuman, Mr John Shim, Ms Ruth Zukerman. SCIENTIFIC ADVISORY BOARD YOUNG APPEALS COMMITTEE The Scientific Advisory Board comprises six internationally-renowned scientists, who carry out an exhaustive evaluation of the Institute’s The Young Appeals Committee was established in 2013 to research programs every five years, to ensure the Institute remains help engage younger audiences with the Institute and its work. at the cutting edge of cardiovascular knowledge generation and Chaired by Mr Marcus Chang, the committee consists of a group continues to produce research of a world-class standard. of dedicated volunteers and staff, committed to raising funds to support research. Members • Professor Doug Hilton (Chair) – Director Walter and Eliza Hall Members Institute, Australia Mr Marcus Chang (Chair), Ms Sally Buist, Ms Keren Weiss, Mr • Emeritus Professor John Chalmers – Senior Director and Head, Julian Cook, Ms Catherine Dearnley, Ms Jenna Klug, Mr Adam Professorial Unit, The George Institute for International Health Buist, Mr Anthony Collins, Ms Daniela Elser, Ms Lauren Palmer, and University of Sydney, Australia. Mr Alistair Booth, Mrs Michele Parker, Mr Ashley Parker, Ms Noura Cheded, Ms Hayley Dodman, Ms Eliana De Sousa. • Professor Witold Filipowicz – Professor of Biochemistry, Friedrich Miescher Institute for Biomedical Research (FMI), FINANCE COMMITTEE Switzerland. The Finance Committee is responsible for the oversight of • Professor Lily Jan – Jack and DeLoris Lange Professor of finances for the Board of Directors. The Committee oversees Physiology and Biophysics, University of California, USA. the audit of the Institute’s accounts, investment management, • Professor Janet Rossant – Chief of Research, The Hospital for management remuneration, and also sets finance policy for Sick Children, Canada. management to follow. • Professor Stephen Vatner – Chairman, Department of Cell Biology Members and Molecular Medicine, New Jersey Medical School, USA. Mr David Craig (Chair), Professor Robert Graham, Mr John Kean, FACULTY REVIEW COMMITTEE Mr Chum Darvall, Dr Gary Weiss, Ms Jan Savage, Ms Janina The Faculty Review Committee comprises eminent scientists Jancu and Mr Kiran Narsey. from local research organisations who evaluate individual faculty members every five years in order to evaluate their productivity, MEDIA AND COMMUNICATIONS promote the development of goals and expectations, foster and COMMITTEE support faculty development and mentorship, and guide junior The Media & Communications committee is responsible for the faculty in career advancement. overall strategic direction of marketing and communications Members activities at the Institute. The Committee meets bi-monthly and seeks to bring new ideas in traditional and emerging media • Professor John Shine (Chair) – Professor of Medicine and platforms to promote the work of the Institute. Professor of Molecular Biology, The University of New South Wales, Group Leader Neural Stem Cells, Garvan Institute of Members Medical Research. Ms Jill Margo (Chair), Mrs Louise Di Francesco, Mr Angelos • Professor Peter Gunning – Head, Oncology Research Unit in the Frangopoulos, Professor Robert Graham, Ms Hayley Dodman, School of Medical Sciences, The University of New South Wales. Ms Janina Jancu, Ms Jan Savage. • Professor John Rasko – Professor of Medicine, Central Clinical School, The University of Sydney and Centenary Institute of Cancer Medicine & Cell Biology. • Professor Phil Robinson – Head, Cell Signalling Unit, Children’s Medical Research Institute, Westmead.

ANNUAL REPORT 2013 15 Our Committees (continued)

COMMITTEE ON APPOINTMENTS INTELLECTUAL PROPERTY AND AND PROMOTIONS COMMERCIALISATION COMMITTEE The Committee on Appointments and Promotions meets on an The Intellectual Property and Commercialisation Committee ad hoc basis to evaluate potential candidates for faculty positions (IPCC) is responsible for advising the Institute on its research within the Institute. commercialisation activities. The Institute has also appointed consultants TM Ventures to assist with linking our research to Members industry and forming new collaborations. • Professor Robert Graham (Chair) – Executive Director, Victor Chang Cardiac Research Institute. Members • Professor Terry Campbell – Senior Associate Dean, The • Professor Robert Graham (Chair) – Executive Director, University of New South Wales. Victor Chang Cardiac Research Institute. • Professor David Celermajer – Scandrett Professor of Cardiology, • Professor Roland Stocker – Head, Vascular Biology Division, Central Clinical School, The University of Sydney and Heart Victor Chang Cardiac Research Institute Research Institute • Dr Trevor Davies – Partner, Allens Arthur Robinson • Professor Richard Harvey – Co-Deputy Director, Victor Chang • Professor Joan Dawes – Senior Consultant, Pestat Ltd; Cardiac Research Institute. and Innovation Dynamics consulting group • Professor Doug Hilton – Director, The Walter and Eliza Hall • Ms Hannah Brown – Senior Associate, Baker McKenzie Institute • Ms Elisabeth White – Senior Associate, Baker Mckenzie • Professor Levon Khachigian – Centre for Vascular Research, • Ms Janina Jancu – Chief Operating Officer, Victor Chang The University of New South Wales. Cardiac Research Institute • Professor Charles Mackay – Department of Immunology, • Ms Britt Granath – Senior Policy Officer, Victor Chang Cardiac Monash University, Melbourne. Research Institute • Professor John Mattick – Executive Director, The Garvan Institute of Medical Research • Professor Jamie Vandenberg – Co-Deputy Director, Victor Chang Cardiac Research Institute. • Ms Maria Voukenas – Human Resources Manager, Victor Chang Cardiac Research Institute

The Institute’s major annual fundraising event – The Victor Chang Gala Ball is organised by the Victor Chang Day Organising Committee.

16 Victor Chang Cardiac Research Institute Research Divisions: CARDIAC PHYSIOLOGY Overview AND TRANSPLANTATION DIVISION Feneley Laboratory Macdonald Laboratory O’Rourke Laboratory Keogh Laboratory Muller Laboratory

DEVELOPMENTAL AND STEM CELL BIOLOGY DIVISION Harvey Laboratory Dunwoodie Laboratory Kikuchi Laboratory

MOLECULAR CARDIOLOGY AND BIOPHYSICS DIVISION Graham Laboratory Vandenberg/Hill Laboratories Fatkin Laboratory Martinac Laboratory

MOLECULAR, VASCULAR STRUCTURAL BIOLOGY AND DIVISION COMPUTATIONAL Stocker Laboratory BIOLOGY DIVISION Stock/Lee Laboratories Suter Laboratory Ho Laboratory

ANNUAL REPORT 2013 17 Cardiac Physiology and Transplantation Division

FENELEY LABORATORY Professor Michael Feneley AM heads up the Institute’s Cardiac Another research focus has been the role of a class of molecules, Physiology & Transplantation Division, in addition to leading his called alpha receptors, in modulating cardiac performance own laboratory, the Cardiovascular Mechanics Laboratory. and hypertrophy. A large part of this work has been done in collaboration with the Institute’s Graham Laboratory. The Cardiovascular Mechanics Laboratory investigates the contractile properties of the heart, and how these properties Many other collaborative projects with researchers inside and change in different disease states based on investigations in outside the Institute are based on the Feneley Laboratory’s animal models of a variety of cardiac diseases. methods to assess cardiac physiology in the whole organism, in the heart isolated from the circulation, and in individual The major research focus of the laboratory is the molecular cardiac cells. signalling pathways that trigger growth of heart muscle cells (hypertrophy) in response to increased heart workload.

Improving heart failure survival, better heart transplants – saving more lives.

18 Victor Chang Cardiac Research Institute MACDONALD LABORATORY The miracle of heart transplantation sees the generosity of organ donors providing recipients with the gift of life. And while transplantation is by far the most effective treatment option for patients with severe heart failure, a chronic shortage of donated organs means it is available to just a small percentage of the people who could benefit. Tragically in Australia, and other countries around the world, many of those who need a new heart will die on the donor waiting list. Throughout 2013, Professor Peter Macdonald’s research team continued their groundbreaking work on novel methods of donor management and donor heart preservation, with the aim of being able to extend this life-saving treatment to a larger number of Australians. More information on their work is featured in Science in the Spotlight (p.23).

ANNUAL REPORT 2013 19 Cardiac Physiology and Transplantation Division

O’ROURKE LABORATORY KEOGH MULLER Secrets of the Arterial Pulse LABORATORY LABORATORY Michael O’Rourke, with collaborator Professor Alberto Avolio and Professor Anne Keogh Under the leadership of three Macquarie University PhD students, analyse, and interpret, runs a research program Associate Professor David pressure and flow waveforms obtained in clinical practice at: at the Institute that Muller, the Muller Laboratory focuses on pulmonary investigates new treatments 1. University of Cambridge and Addenbrooke’s Hospital, arterial hypertension, to prevent, treat and reverse Neurosurgical Intensive Care (Dr Marek Czosnyka, Professor of heart transplantation, coronary artery disease, and to Brain Physics). Aortic pressure waves, intracranial pressure waves, immunosuppression and understand inciting factors that and intracranial artery flow waves are obtained in unconscious left heart failure. trigger heart attacks, including patients at high risk of secondary stroke and death following shear stress related changes in This is in addition to her role closed head trauma. Aim is to improve monitoring and treatment. platelet function. as a Senior Heart Transplant 2. Oslo University Hospital, Department of Neurosurgery (Dr Cardiologist in the Heart A recent focus of the team P.K. Eide). Aim is similar, but includes treatment of patients with Transplant Unit of St Vincent’s has been novel approaches to hydrocephalus, subarachnoid haemorrhage and major stroke, with Hospital. management of valvular heart emphasis on secondary events attributable to pulsatile phenomena. disease, and evaluating the Professor Keogh’s research impact of therapies on shear 3. Hopital George Pompidou, Paris, Dept of Cardiology/MRI aims to find the best-tailored stress, platelet function and Imaging (Prof Eli Mousseaux). Aim is to improve measurement therapy for individual patients clotting parameters. of ascending aortic flow from the heart through use of MRI, and with Class-I-IV heart failure, to study effects of aortic aging on the heart, brain, kidney in time including drug therapy, and frequency domains. synchronised pacing and 4. Wels General Hospital, Dept. of Cardiology, Austria (A/Prof ventricular assist devices. T. Weber). Aim is to characterise LV-vascular interaction using Professor Keogh was recently ultrasonography, and to compare results with MRI and central awarded an Order of Australia aortic pressure techniques. (OA) for her services to cardiac 5. Continuing work begun in the 1970s by Victor Chang, studies at transplantation, heart failure, Ruijin Hospital, Shanghai, Hypertension Department (Drs J. Wang, pulmonary hypertension and L. Yan). A study of flow waves in cerebral arteries with central animal welfare. aortic pressures has been completed in 1020 subjects, This has provided unique new information on changes with age that are relevant to mechanisms of small arterial disease and dementia. 6. Massachusetts Institute of Technology, Harvard Medical School, Boston (Dr E. Edelman). Aim is to explore the relationship between aortic stiffening (and de-stiffening) on pulsatile flow in the human brain, and cerebral vascular disease. This embraces possibility of treating extreme aortic stiffening through application of an elastic wrap to the aorta. 7. Sydney University, Brain and Retinal Biology (Prof J. Stone). Aim is to explain pathological changes in the brain of older humans on the basis of aortic stiffening and high pulsatile flow in small arteries.

20 Victor Chang Cardiac Research Institute CLINICAL FACULTY HONORARY FACULTY FACULTY-AT-LARGE > Dr Kumud Kumar Dhital > Dr Ahsan Husain > Professor Livia Hool > Associate Professor Chris Hayward > Dr Andrew Owens > Dr Andrew Jabbour > Dr David Martin > Associate Professor Jane McCrohon > Professor Matthias Hentze > Dr Phillip Spratt > Professor Soren-Peter Olsen > Associate Professor Rajesh Subbiah > Associate Professor David Winlaw > Associate Professor Jacob Sevastos > Dr Andras Nagy > Associate Professor Cameron Holloway > Professor Thomas Preiss

ANNUAL REPORT 2013 21 This pioneering research could lead to an increase in the heart organ donor pool by 15-20 percent, possibly more

22 Victor Chang Cardiac Research Institute Science in the Spotlight

RESEARCH HELPS DONOR HEARTS TO BEAT AGAIN In November 2013, Professor Peter Macdonald, co-head of the Cardiac Transplantation Laboratory, reported that his team of researchers have found a way to protect hearts that have stopped beating, in what is know as circulatory death, and bring them back to life outside the body. Presenting at the congress of the International Society of Organ The team has developed a special solution, which prevents the Donation and Procurement in Sydney, Professor Macdonald donor heart cells from dying. They then take the heart and revealed this pioneering research could lead to an increase in the attach it to a machine that pumps the donor’s own blood into heart organ donor pool by 15 – 20 per cent, possibly more. it, which enables it to start working outside the body before it’s implanted into the recipient. “Until now, we were not able to use the hearts from people who donated their organs after withdrawal of life support. Once Dr Arjun Iyer, research fellow, commented: “It’s very important you withdraw life support, there is no oxygen going into the for people to understand there’s no attempt to reanimate the body and all the organs suffer, but especially the heart which has heart in the donor, this is all done outside the body. much higher oxygen requirements than other organs used for “It’s affectionately known as the ‘heart in the box’. To date, we transplantation such as the kidney, liver or lungs. have successfully reanimated two human hearts, and carried “While Australia’s organ donation rate has been going up, the out the full transplant on a dozen animals. This process adds a increase has really been in the types of donors who aren’t really whole level of complexity to resuscitating these organs, but it is suitable for heart transplantation, so there’s only been a very small one we are happy to take on board.” increase in heart transplants”, Professor Macdonald said. For more information on organ donation visit www.donatelife.gov.au

ANNUAL REPORT 2013 23 Developmental and Stem Cell Biology Division

HARVEY LABORATORY DUNWOODIE LABORATORY The Harvey Laboratory, led by Deputy Director Professor Richard Three percent of all babies born have some form of birth defect. Harvey, studies how the heart forms in the embryo and how it In some instances they are not life threatening, but they do cause repairs itself in the adult. disability and distress. In others, they are life threatening and surgery, often many times over, is required. The heart begins to function after only a few weeks of embryonic life, when it is still a simple muscular tube. As heart structure In only about 20 per cent of cases is the cause of the defect develops further through the addition of valves, specialised understood, leaving thousands of families each year in Australia chambers and a more sophisticated electrical system, its function wondering why they have been affected. also becomes more adapted to the needs of the growing embryo. Research in the Embryology Laboratory, led by Professor Sally The forming heart seems especially vulnerable to defects in Dunwoodie, is focused on embryonic development, as birth the genes that control its formation, and this is why structural defects arise if developmental processes are disrupted. malformations of the heart (congenital heart disease) are The Dunwoodie Laboratory seeks to understand what factors relatively common in newborn children. are likely to disrupt the developmental process, whether it is The Harvey Laboratory is looking to understand how gene the genetic code of the embryo, environmental factors during defects cause heart defects, and how this information can be gestation, or a combination of both. used to help families with congenital heart disease. The team is identifying genes that are required for the normal In 2013, they made a major advance in proving a vital role for development of the heart or vertebral column, and looking the gene Nkx2-5 in formation of the large outflow vessels of at whether they are altered in babies born with defects. The the heart (see Science in the Spotlight, p.26). Laboratory is also exploring how environmental insults during gestation, such as low oxygen (hypoxia), impact on embryo In the adult, heart attack is common, claiming the lives of more development. than 20,000 Australians each year. The death of large segments of heart muscle is not easily repaired naturally, but there is hope that if we can understand how other types of tissues regenerate, we can encourage this to occur in the injured heart. Thus, another challenge in the Harvey Laboratory is to address how stem cells (a type of unspecialised cell with a ‘blank slate’, that can be turned into any cell type in the body) could be used to repair the heart after insult or injury.

24 Victor Chang Cardiac Research Institute KIKUCHI LABORATORY After insult or injury, can damaged heart tissue get its function back? The main aim of the Cardiac Regeneration Laboratory, led by Dr Kazu Kikuchi, is to understand the mechanisms of heart regeneration. In mammals (including humans), the heart does not regenerate after damage from an insult such as a heart attack. Instead, the damaged tissue is replaced by fibrotic scar tissue, which provides quick repair from the damage, but fails to restore cardiac function and increases susceptibility to heart failure. In contrast, some vertebrates such as salamander and fish are known to naturally regenerate heart muscle with little scar formation after injury. The Kikuchi Laboratory uses zebrafish, a smalltropical freshwater fish which is highly amenable to genetic manipulations, to study the molecular and cellular regulations of heart muscle regeneration. The group has a long-term objective of finding out how this type of regeneration might be used to repair damaged human hearts.

ANNUAL REPORT 2013 25 Science in the Spotlight

GENE VITAL TO FORM HEARTS ‘LARGE VESSELS’ Publishing in the prestigious journal Nature Cell Biology in October 2013, Professor Richard Harvey and his team reported for the first time the vital role played by a single gene in forming the hearts ‘large vessels’. In collaboration with colleagues at Massachusetts General Professor Harvey, Head of the Developmental and Stem Cell Hospital and Harvard Medical School, the Harvey team explored Biology Laboratory commented: the role of the heart regulatory gene Nkx2-5 in both zebrafish “In this study we were looking at the arteries of the pharyngeal and mouse embryo models, and discovered that in the absence region, a complex network of vessels which are laid down during of this gene the large vessels leading out of the heart did not embryonic life. These go on to be remodeled in response to form properly. the emerging blood flow to form part of the aorta, the largest This included the aorta, the major vessel that supplies the upper vessel in the body, and arteries of the head and neck that are body and head with oxygenated blood. fed directly by the heart. In babies, sections of these large vessels are sometimes “In the absence of this particular gene, we showed these constricted or missing, which can be life threatening. In Australia, important arteries simply could not form, and so our work may congenital heart disease is the biggest killer of children under five shed new light on how faults in certain gene pathways lead to years of age. vascular defects in babies. While the primitive blood vessel-forming cells were created and “To make progress in managing congenital heart disease, located normally in embryos lacking Nkx2-5, they could not we need to understand how such conditions arise and progress. express genes reflecting a specialised vessel lining or join together Our ultimate goal is to help prevent its potentially devastating to form a network of functional vessels. onset, and the significant pain and suffering these conditions can bring to both affected babies and their families.” The Nkx2-5 gene acts much like an orchestra conductor, telling heart cells with precise timing when they should specialise, grow and divide. In fruit flies, mutations in the equivalent of the Nkx2-5 gene stop the heart from forming altogether, resulting in it being dubbed the ‘Tinman’ gene (after the Wizard of Oz character, who had no heart).

To make progress in managing congenital heart disease, we need to understand how such conditions arise and progress

26 Victor Chang Cardiac Research Institute ANNUAL REPORT 2013 27 Molecular Cardiology and Biophysics Division

GRAHAM LABORATORY VANDENBERG/HILL LABORATORIES What switches the heart on during times of ‘flight or fight’? Can we predict a person’s risk of sudden cardiac death, and Can we mend a broken heart? personalise a treatment plan to prevent it? There are two key focuses of work in the Graham Laboratory, In March 2012, 23-year-old Bolton Wanderers footballer Fabrice which has Institute Executive Director Professor Bob Graham Muamba suffered a cardiac arrest on the pitch. His case captured at the helm. the attention of the world, and he was later diagnosed with an arrhythmia (when the heart beats in an irregular fashion), which The first looks at the key which switches the heart ‘on’. places an individual at risk of sudden cardiac death. In August We have all experienced a pounding heart when we are angry, that year, he retired from football aged just 24. or during times of heightened anxiety. This is caused by the The Cardiac Electrophysiology Laboratory, led by Deputy Director, hormone adrenaline being released by the body, causing an Professor Jamie Vandenberg and Group Leader, Dr Adam Hill, adrenaline rush. focuses on how disturbances in the electrical activity of the heart The adrenaline acts as a key to unlocking specific switches can result in arrhythmia. (adrenergic receptors) on the surface of heart cells, telling them Arrhythmia is one of the most common causes of death, and to beat faster. for many people at risk of sudden arrhythmic death, the only The Graham Laboratory studies the structure and function of effective treatment option is an implantable defibrillator. These these switches, which during times of ‘fight or flight’ response devices are expensive, and come with significant side effects. are critical to our survival, but when over-activated can cause In understanding whether the potential benefit of the defibrillator abnormal heart rhythms, high blood pressure and thickening outweighs the risk, it is important to be able to assess the odds of the heart muscle. of sudden cardiac death in the individual. This is currently very The team is also carrying out research aimed at improving the difficult to do, and is a major area of focus for the team. very limited capacity of heart muscle cells to divide. Using a range of techniques (including a 3D computerised model This important work could benefit patients who have suffered of the heart), they are investigating the molecular mechanisms a heart attack, by allowing their broken hearts to be repaired that control the electrical activity in the heart. The team seeks properly, rather than merely through the development of scar to understand how these mechanisms might be disordered in tissue, which impairs the pumping function of the heart resulting patients with inherited heart diseases and how environmental in heart failure or death. factors may increase the risk of arrhythmia. They are also investigating whether there are biomarkers on patients’ ECGs that may help improve stratification of risk in patients with heart disease.

28 Victor Chang Cardiac Research Institute Cutting-edge technologies to uncover the genetic variants in families with inherited heart diseases

FATKIN LABORATORY MARTINAC LABORATORY Inherited gene variants are recognised as increasingly important How does the heart respond to stress? causes of heart disease, but very little is known about what these Humans and animals are able to perceive vibrations when they genetic factors are, and how they affect heart function. hear something, or something touches their skin. Even our heart The Fatkin Laboratory focuses on two of the most common heart cells can tell when something is touching them. disorders, dilated cardiomyopathy (where the chambers of the When the heart is beating and pumping blood, its cells feel the heart enlarge and the pumping action becomes weak) and atrial motion and respond by sending an electrical current throughout fibrillation (when the heart beats in an irregular fashion, also the heart. known as an arrhythmia). This current is made possible by a type of protein known as an The team is using cutting-edge sequencing technologies to ‘ion channel’, which pokes through the membrane of the cell. It ‘read’ the genetic code contained in each persons DNA. They are acts much like a tap on a hose, opening to let ions flow through looking for the ‘spelling mistakes’ contained in the code, which the cell membrane, and closing to shut off the electrical current. alter the proteins in the heart. In bacteria these ion channels act as ‘safety valves’ protecting These studies are only possible with family participation, and the bacteria from drastic changes in the salt concentration of its many hundreds of enthusiastic family members have been environment. enrolled into this area of research. The Martinac Laboratory study bacterial mechanosensitive ion One of the biggest challenges in genetics research is working channels as they function in roughly the same way as human out which of the thousands of genetic variants that each person ion channels. carries are causative of heart disease. 2013 was an outstanding year for the Laboratory’s leader, the To address this need, the Fatkin Laboratory use zebrafish as illustrious Professor Boris Martinac, as he was elected as a Fellow models. A key achievement in the last 12 months has been the to the Australian Academy of Science. generation of the first transgenic zebrafish model of a human arrhythmia mutation. Representing Australia’s leading research scientists, the Australian Academy of Science host an annual celebration for a small The overall aim of these studies is to better understand the number of scientists, where their outstanding contribution to mechanisms of heart disease, in order to find new, personalised, the field is officially recognised by election to the Academy. approaches to patient care. Building on a highly successful year in 2012, 2013 saw Diane Fatkin promoted to Professor of Medicine by the University of New South Wales and scoop the Eric Susman Prize. Awarded by the Royal Australian College of Physicians, it honours ‘the best contribution to the knowledge of any branch of internal medicine’.

ANNUAL REPORT 2013 29 Science in the Spotlight

NEW ERA MEDICINE: REVERSAL OF AN ENTIRE FAMILY’S HEART RHYTHM DISORDER In a world first, a team of researchers led by Professors Diane Fatkin and Jamie Vandenberg used gene-based therapy to successfully reverse an inherited heart rhythm disorder in members of an entire family.

Some of the family members had previously been told they had “This was game-changing research. only months to live, and this therapy, heralded as part of the “Whilst we can only claim to have treated one particular new era of personalised medicine, achieved remarkable results. mutation that causes cardiac dysfunction, and there is still much The findings were published in the Journal of the American more to do to find the genetic causes of heart disease in every College of Cardiology. family, this is a huge step in the right direction. Rather than using conventional heart failure medicine, the “Throughout 2013 we have continued the clinical follow-up of researchers identified and treated the gene mutation that caused the family members with this particular mutation, and they are the family’s heart rhythm disorder, dilated cardiomyopathy. making good progress. We also progressed in genetic testing of the younger family members, with at least one extra person Dilated cardiomyopathy is a condition where the heart cannot starting on the therapy. pump enough blood to the body, making it a major risk factor for stroke and heart failure. “In addition, we’ve been working hard to recruit other families with both dilated cardiomyopathy and arrhythmias to our Affected family members received a drug shown in laboratory research studies, so that we can continue to find new disease- tests to target the gene mutation. causing gene variants, and novel approaches to treatment.” Professor Fatkin said the results were outstanding, with many patients with severe disease returning to full health within six months.

This was game-changing research. An example of what can be achieved if we know the what, where and why about the underlying gene mutation.

30 Victor Chang Cardiac Research Institute ANNUAL REPORT 2013 31 Molecular, Structural and Computational Biology Division

STOCK LABORATORY SUTER LABORATORY Mitochondria are the ‘powerhouses’ of the body’s cells, Epigenetic marks are laid down in our cells as we develop in the converting food and oxygen into the biological fuel which the womb. Sometimes these marks are placed incorrectly, leading to body needs to survive, as well as to thrive. genes being switched on or off inappropriately. The Structural Biology Laboratory, headed by Dr Daniela Stock, Each of us has a single unique genome, a set of instructions uses X-ray crystallography to determine the structure of proteins made of DNA that creates all the different tissues and cell types involved in this process at near atomic resolution. in our bodies. Crystallography is a vital scientific method for understanding Epigenetic ‘marks’ sit on top of our DNA and dictate which genes the properties of matter. It underpins many fields of study from are switched ‘on’ or ‘off’ in a given cell. This allows our DNA to inorganic minerals to biological material and yet remains relatively generate the diversity of cell types we need from just a single set unknown to the public. of instructions. X-ray crystallography is used to determine the atomic structure of The Epigenetics Laboratory, led by Associate Professor Cath Suter, crystalline material. The unique spots of X-rays diffracted by the is interested in understanding how this incorrect setting occurs. crystal reveal the arrangement of atoms within the crystal. The team has focused on how a mother’s diet during pregnancy As Nobel laureate Max Perutz used to say it shows “why blood can influence the setting of epigenetic marks that may in turn is red, grass is green, why diamond is hard and wax is soft, why influence the health of her children, and even grandchildren or graphite writes on paper and silk is strong.” beyond, in their adult life. The work of the Stock Laboratory visualises proteins at extremely In 2013, they also turned their attention to diet and health of high resolution, which is essential in understanding their function fathers. Their early data shows that a father’s health also impacts in health and disease, and how they interact with other proteins on the health off his offspring (ruling out genetic effects), and that and with drugs. again there is an ‘epigenetic memory’ of the father’s exposure that influences health in his children, and possibly grandchildren too.

32 Victor Chang Cardiac Research Institute Visualising molecular power generators at atomic resolution

LEE LABORATORY HO LABORATORY The human body is made up of hundreds of billions of cells. The Bioinformatics and Systems Medicine Laboratory, headed by one of Australia’s rising scientific stars, Dr Joshua Ho, was What happens inside our cells is responsible for the function established in July 2013. of our tissues, organs and bodies in health and disease. The Laboratory has expanded the Institute’s capacity in the Inside each cell there are tens of thousands of sophisticated cutting edge field of Bioinformatics, the application of computer biological machines that operate efficiently to keep our bodies science, mathematics and statistics to understand how complex functioning normally. biological systems work, and how genetic or molecular defects in The Molecular Motors Laboratory, led by Dr Lawrence Lee, these systems lead to diseases. seeks to understand how these machines look and function In many cases, determining whether a heart disease patient and at an atomic scale. their family members carry specific gene mutations in the DNA The Laboratory is taking a fundamentally new approach to the is critical for genetic counselling and informing the best course study of the biological sciences at the molecular level: to study of treatment. biological machines by constructing them from the bottom up. Using state-of-the-art sequencing technology, we can now Using a new tool, DNA self-assembly, the Lee Laboratory is routinely generate a large volume of DNA sequencing data. building atomically precise ‘nanoscale’ structures to scaffold the However, the real challenge lies in sifting through this to pinpoint assembly of some of nature’s largest biological machines. the disease-causing mutations – akin to searching for a needle in a haystack. This includes the production of the bacterial flagellar motor, a highly efficient rotary motor that rotates five times faster than a The Ho Laboratory employs innovative computational Formula One engine, and bacteria’s molecular syringe, the type III approaches to significantly speed up the pace of discovering secretion system, which injects virulence factors directly into the disease genes, as well as deciphering how genetic and non- cells of infected patients. genetic factors act together to cause heart diseases. This may lead to the development of new antibacterial vaccines Dr Ho, at age 28, is the youngest faculty member the Institute that are less susceptible to antibiotic resistance. has ever had. He undertook his postdoctoral training at the world-renowned Harvard Medical School in the United States, has published many peer-reviewed journal papers and is currently a conjoint senior lecturer at the University of New South Wales.

ANNUAL REPORT 2013 33 Science in the Spotlight

WHILE MUM’S PROGRAM THEIR CHILDREN TO BE FAT, THE LEGACY CAN BE OVERTURNED Study published in Epigenetics

Scientists in the Epigenetics The study was carried out by By using genetically identical After two months, they had Laboratory discovered that leading researchers Associate mice as a model, the team developed severe fatty liver obesity and type 2 diabetes Professor Cath Suter and Dr investigated the effects of disease. The offspring of lean in pregnancy can program Jennifer Cropley, and published having a mother with obesity mothers remained normal on children to develop metabolic in the journal Epigenetics in and type 2 diabetes. the same Western diet. problems later in life. June 2013. The research team found But the news isn’t all bad. However, this legacy is not set Lead author on the study, that the offspring of obese The offspring of obese in stone, and if the children Associate Professor Suter, says and diabetic mothers were mothers, while heavier and of obese mothers are careful little has been understood predisposed to developing fatter, could be protected from about what they eat, it can until now about how being metabolic disease, and that overt metabolic disease and be overturned. overweight in pregnancy males were particularly fatty liver by sticking to a impacts on the future health affected. low-fat diet. of children. These offspring were heavier than the offspring of lean mothers – even as babies, and when weaned onto a Western-style ‘junk food’ diet, they developed the hallmarks of type 2 diabetes within a few weeks.

34 Victor Chang Cardiac Research Institute ANNUAL REPORT 2013 35 Vascular Biology Division

STOCKER LABORATORY The Stocker Laboratory, headed by Professor Roland Stocker, aims to better understand atherosclerosis, which is the hardening and narrowing of the arteries, the blood vessels that carry blood from the heart through the body. The arteries are lined by a thin layer of cells called the endothelium, which works to keep the inside of the arteries toned and smooth, and therefore keeps blood flowing. Atherosclerosis starts when high blood pressure, smoking, or high cholesterol damage the endothelium, at which point cholesterol plaque formation begins, entering the wall of the artery. This progressive process silently and slowly blocks the arteries, putting blood flow at risk. It is the most common cause of heart attacks, strokes and peripheral vascular disease, known collectively as ‘cardiovascular disease’. The Stocker Laboratory is part of the Vascular Biology Division, which formed in late 2012 and brought a completely new dimension of research to the Institute. How do our arteries harden and narrow?

36 Victor Chang Cardiac Research Institute VASCULAR BIOLOGY COMES TO It was the Institute’s very strong focus on research-based outcomes that proved pivotal in attracting Professor Stocker, THE CHANG who has published over 250 papers internationally. In 2012, highly acclaimed Vascular Biologist Professor Roland Stocker joined the Institute to head up the new Vascular “There are many benefits to working, and leading a team of Biology Division. scientists, here. First and foremost is the incredibly strong culture, unwavering in its outcome-focused approach. Over the last year, the Vascular Biology Program has brought a completely new dimension to the Institute’s work, looking at “As a career scientist, that gives me a great joy and a buzz every the body’s blood vessels, or ‘pipes’, where other divisions focus day that is more important than any pay cheque. The Institute on the heart, or ‘pump’. also has an incredible leadership team with Bob Graham at the helm”, he said. The team is made up of 12 researchers who are addressing three key areas - what goes wrong in the blood vessels, how they It’s a busy life too for Professor Stocker outside of the Laboratory. become diseased, and how that process can be halted. In the 1970’s he participated on behalf of his home country, Professor Stocker said: “Most cardiovascular disease is caused Switzerland, in the rowing world championships in New Zealand, by a fault in the pipes. To do its job effectively in pumping blood and it was his passion for the outdoor lifestyle led him to migrate around the body, the heart needs the blood vessels to be in good permanently to Australia in 1988. condition too. He and his wife Maree are also keen skiers, and recently became “It makes perfect sense to be carrying out this work here because grandparents for the first time. it aligns so closely with the cardiac research already going on, especially within the Cardiac Physiology & Transplantation Division. “Understanding the processes involved in diseased blood vessels is vital in helping us establish whether we can reverse the process through the development of new drug therapies, or medical devices.”

ANNUAL REPORT 2013 37 Awards and Achievements 2013

ACCOLADES Professor Boris Martinac, Head of the Mechanobiology Laboratory, was elected to Fellowship of the Australian Academy of Science. Co-Deputy Director of the Institute, Professor Richard Harvey, received the 2013 Ministerial Award for Cardiovascular Research. Professor Diane Fatkin, Head of the Sr. Bernice Inherited Heart Diseases Laboratory, was promoted to Professor of Medicine, University of New South Wales. She also received the Royal Australasian College of Physician’s ‘Eric Susman’ prize for her outstanding contribution to internal medicine, Dr Andy Ng (Vandenberg Laboratory) received the young biophysicist award at the 37th annual conference of the Australian Society for Biophysics DEGREES AWARDED Five people were awarded PhD degrees in 2013 from the University of New South Wales. Sara Ballouz and Dhakshinari Hulugalle (Stock Laboratory), Juliane Heide (Vandenberg Laboratory), Alex James (Dunwoodie Laboratory) and Christiana Leimena (Fatkin Laboratory). LIFE GOVERNORS AND AMBASSADORS In 2013, we welcomed five new Ambassadors, one new Young Ambassador, and a new Life Governor to the Institute, for their dedication, commitment and encouragement to our research. Their support has been unwavering, their loyalty unsurpassed. PATRONS AMBASSADORS Mrs Ann Chang (2004) Mrs Jennie Thomas (2002) Mr John Laws, CBE (2001) Mr Steve Quinn (2011) The Hon Neville Wran, Lady Mary Fairfax, AM,OBE The late Ms Amana Finley Cobram Estate (2011) AC, QC (2008) (2003) (2001) Ms Anne-Marie Allgrove Mr Ziggy Switkowski (2003) Mr Ken Laing, AM (2001) (2011) PAST PATRON Mr Sam Chisholm (2003) The late Mr Alan David (2002) United Airlines (2011) The Late Mr Kerry Packer, ANZ Bank (2004) Crane Group Limited (2002) Virgin Airlines (2012) AC (1994) Citigroup (2005) Steve Costi Seafoods (2003) Mr Terry McCabe (2012) HONORARY LIFE Mr James Packer (2005) Crestbrook Mountain Springs Mr Mark Ryan (2012) GOVERNOR Mr Mark Johnson (2006) (2003) HCF (2012) Baker & McKenzie (2004) Her Royal Highness Crown Mr Lance Rosenberg (2006) Ms Michelle Parker & Princess Mary of Denmark Mr Ken Lee (2007) Schute Bell Badgery Lumby Ms Emma Quick (2012) (2005) (2005) The Atlantic Philanthropies Randwick City Council (2013) (2007) Mr and Mrs David & Diana Kia Motors (2013) Ritchie (2005) LIFE GOVERNORS Mr & Mrs David & Diana Ryan Stokes (2013) Mr and Mrs Scott & Rhonda Mrs. Barbara Ell (2000) Ritchie (2007) Craig Marshall (2013) Gibbons (2006) The late Lady Finley (2000) John T Reid Charitable Trusts Sharlene Melville (2013) Mr John David (2000) (2008) Mr and Mrs Russell & Julieanne Cooper (2007) Mr Frank Lowy, AC (2000) Inghams Enterprises (2008) HONORARY LIFE Mr and Mrs John & Margaret Mrs Roslyn Packer, AO (2009) MEMBERS Strathfield Car Radios (2000) Ingram (2007) Mr Lionel Lee (2010) Ms Fiona Coote, AM (2001) The Freshest Group (2000) Mr and Mrs Ralph & Lorraine Mr Kerry James, AM (2004) Abigroup (2000) Mr and Mrs Gerry & Wendy Keyes (2008) Commerford (2010) Mr John Kean (2010) Freedman Foundation (2000) Guinness Peat Pty Ltd (2008) Chain Reaction (2012) Mr John McGuigan (2010) National Australia Bank (2000) Mr Cameron Irving (2009) De Groot Industries (2013) Mr Robert Oatley, AO (2001) Deutsche Bank (2009) YOUNG Mr Steven Lowy, AM (2001) Club Marconi (2009) AMBASSADOR Telstra Corporation (2001) LK Jewellery (2009) Mr Mark Vincent (2009) Ms Kate Ritchie (2013)

38 Victor Chang Cardiac Research Institute Discovery begins with individuals. Many of ours received accolades of the highest honour in 2013.

Clockwise from top left: > Ryan Stokes > Bob Graham, Craig Marshall and Steven Lowy > Alan Crouch (Kia Motors) > Randwick Mayor, Councillor Scott Nash and Sharlene Melville (Randwick City Council) > Kate Ritchie > Gary Wong (De Groot Industries)

ANNUAL REPORT 2013 39 Paul Korner Seminar Series

2013 Paul Korner winner The Paul Korner Seminar Series is presented weekly, providing our young scientists Stefan Mann the opportunity to present an update of their research progress and achievements. The Series was established in 1998 to recognise the outstanding contributions of Professor Paul Korner, a pioneer of cardiovascular research in Australia. Professor Korner sadly passed away in October 2012.

Louise Dunn “A novel role for heme oxygenase-1 in peripheral vascular disease” David Humphreys “Analysing transcriptome complexity with high throughput sequencing” Maryrose Constantine “TRPping out in the membrane - structural and mechanobiological investigations of TRPM4” Inken Martin “Zebrafish models of heart failure and arrhythmia” Duncan Sparrow “Genetic and environmental causes of vertebral and heart defects” Charles Cranfield “Antimicrobial Peptide Insertion Into Lipid Membranes” Romaric Bouveret “Congenital heart diseases and macarons” Gavin Chapman “Ligand-induced trafficking of the Notch1 receptor” David Langley “Antibodies – formats, evolution and utility” Elise Laming “Investigating the proton channel of the A-type rotary ATPase” Sally Eaton “Multi-generational metabolic programming by parental obesity” Nicole Schonrock The Transcriptional Landscape Surrounding Nkx2-5: Finding a forest among the trees… Siiri Iismaa “Cardiomyocyte proliferation during preadolescent growth and after myocardial injury” Callum Smits “Towards structural characterisation of the MS-ring of the bacterial flagellar motor” Jane Yu “Critical role of RHOA/ROCK signalling in cardiac contractility” Alexis Bosman “Identifying the Genetic Cause of Hypoplastic Left Heart using iPSC” Mirana Ramialison “Decoding heart development” Arjun Iyer “Donation after circulatory death (DCD) donors in cardiac transplantation - Back to the future?” Gayathri Kumarasinghe “Enhancing preservation of hearts from brain-dead donors: “turning bad into good” James Cornwall “Quantifying Cardiac Stem Cell Growth Dynamics using Time-Lapse Imaging and Single-Cell Tracking” Hafizah Hamid “A role for heme oxygenase-1 in embryonic development?” Ghassan Maghzal “Bleach in atherosclerosis: Does it matter and how do we detect it?” Ali McCorkindale “Investigating expression and function of a Piwi protein in stem cells and cancer” Naisana Seyed Asli “Cell Cycle and Metabolism at the Heart of Stem Cells” Stefan Mann “A Tale of Tails: insights into hERG channel gating” Vesna Nikolova-Krstevi “Evaluation of Mechanical Stretch Responses in the Atrial Endocardium” Roberta Davies “Detection of Conformational Flexibility in the Thermus thermophilus A-ATPase using Mass Spectrometry” ChuKong Liew “Engineering lower-hanging fruit: the bumpy road to GPCR structures”

1st Year PhD Candidates Amy Nicks, Tony Ngo, Lorraine Ganuelas, Navid Bavi, Dhanushi Abeygunawardena

WINNER: STUDENT WINNER: PEOPLE’S CHOICE: Stefan Mann Maryrose Constantine David Langley (Vandenberg Lab) (Martinac Lab) (Stock Lab)

40 Victor Chang Cardiac Research Institute Barbara Ell Seminar Series A rare treat

This Seminar Series is named after Mrs Barbara Ell, a life governor, avid supporter of the Institute and a hard working member of both the Board and Appeals Committee. The Institute invites a renowned Australian scientist to present a lecture as a part of the Barbara Ell Seminar Series.

Dr Manuel Ferreira Genetic Epidemiology Unit, Queensland Institute of Medical Research “Back to humans: how genetic research can point to new drugs for asthma” Dr Sandro F. Ataide Lecturer in Structural Biology, School of Molecular Bioscience, University of Sydney “The Signal Recognition Particle RNA and its multi functions” Professor Simon Foote Dean of ASAM, Macquarie University “Host-parasite interactions and the development of resistance-proof antimalarials” Professor Henry Krum PhD FRACP, Director, CCRE Therapeutics, Monash University “Heart-kidney interactions in heart failure” Professor David Craik Group leader for NMR Spectroscopy research, IMB “Discovery and applications of naturally occurring cyclic peptides in drug design” Professor David James Leader, Diabetes & Obesity Research Program, Garvan Institute of Medical Research; NHMRC Principal Research Fellow; Professor (Adjunct), School of Biotechnology & Biomolecular Sciences, Faculty of Science, University of New South Wales “New insights into insulin action using proteomics” Professor Aleksandra Filipovska ARC Future Fellow, Western Australian Institute for Medical Research “Regulation of mitochondrial gene expression in health and disease” Dr Till Boecking Leader of the Molecular Machines Unit, Centre for Vascular Research “Watching chaperones play molecular jenga”

LEADING INTERNATIONAL KIDNEY Dr Susan Quaggin delivered the DISEASE SCIENTIST GIVES 2013 2013 Princesses Lecture at the 14th Victor Chang Cardiac Research PRINCESSES LECTURE Institute International Symposium. One of the world’s leading scientists in the field of kidney disease, Dr. Susan Quaggin, delivered the 2013 Princesses Lecture at the 14th Victor Chang Cardiac Research Institute International Symposium in December. The theme of the symposium, held in conjunction with St Vincent’s Hospital, was ‘Vascular Biology: from basic science to renal denervation’. The discovery opens up new therapeutic opportunities for developing drugs that either stimulate, or inhibit, blood Quaggin, Professor and Head of the Feinberg Cardiovascular vessel formation, important goals in both cardiovascular and Research Institute and Division of Nephrology at Northwestern anti-cancer therapies. University in Chicago, is currently spearheading work to discover ways to halt the progression of kidney disease through a better Professor Bob Graham, Executive Director, said: “We were understanding of kidney development and function. honoured to have such an outstanding group of experts, which includes some of the world’s leading scientists and clinicians, Her work has already led to the discovery of a gene critical for taking part in our 2013 symposium. kidney, lung and heart development, which is now being used to study the evolution of microscopic kidney filters, whose role “Susan Quaggin’s Princesses’ Lecture was a highlight of three is to remove waste and excess fluids from the blood. days discussion spanning the latest in basic science, right through to application of innovations and discoveries to patients. Other presenters at the three-day event included Professor Michael Simons, Director of the Cardiovascular Research Centre ‘It was an exciting gathering of some brilliant minds, and a terrific at Yale University, Newhaven, Connecticut. Early in 2013, he was example of how researchers can collaborate on problems to part of a team who uncovered the molecular pathway by which strengthen the future of biomedical research and clinical care new arteries may form after heart attacks, stroke and other acute across the globe.” illnesses, bypassing arteries that are blocked.

ANNUAL REPORT 2013 41 Bosman A, Sartiani L, Spinelli V, Cox CD, Nomura T, Gupta R, Flanagan S, Li CCY, Publications Del Lungo M, Stillitano F, Nosi Ziegler CS, Campbell AK, Lee M, Shivalingham B, Maleki D, Mugelli A, Cerbai E, Jaconi Wann KT, Martinac B. S, Wheeler HR, Buckland ME. M. Molecular and functional Selectivity mechanism of the Expanding the spectrum of IDH1 2013 evidence of HCN4 and mechanosensitive channel MscS mutations in gliomas. Mod Path caveolin-3 interaction during revealed by probing channel 2013;26:619-625 cardiomyocyte differentiation subconducting states. Nat Haworth NL from human embryonic Commun 2013;4:2137. , Wouters MA. stem cells. Stem Cells Dev Between-strand disulfides: 2013;22:1717-27. Eaton SA, Hough T, Fischer- forbidden disulfides linking Colbrie R, Peters J. Maternal adjacent beta-strands. RSC Boulos RA, Man NYT, Lengkeek inheritance of the Gnas cluster ADVANCES 2013;3:24680- NA, Hammer KA, Foster NF, mutation Ex1A-T affects size, 24705. Stemberger NA, Skelton BW, implicating NESP55 in growth. Keogh AM Macdonald PRIMARY PAPERS Wong PY, Martinac B, Riley Mamm Genome 2013;24:276-85. Hu SX, , PS TV, McKinley AJ, Stewart SG. , Kotlyar Em Robson D, Ballouz S, Liu JY, George RA, Inspiration from old dyes: Eisen HJ, Kobashigawa J, Harkess M, Granger E, Dhital K, Bains N, Liu A, Oti M, Gaeta Spratt P Hayward CS Tris (stilbene) compounds Starling RC, Pauly DF, Kfoury Jansz P, , . B, Fatkin D, Wouters MA. as potent Gram-positive A, Ross H, Wang SS, Cantin B, Interaction between physical Gentrepid V2.0: a web server antibacterial agents. Chem Eur J Van Bakel A, Ewald G, Hirt S, activity and continuous-flow left for candidate disease gene 2013;19:17980-88 Lehmkuhl H, Keogh AM, Rinaldi ventricular assist device function prediction. BMC Bioinformatics M, Potena L, Zuckermann A, in outpatients. J Card Fail 2013;14:249. Castagnaro L, Lenti E, Maruzzelli Dong G, Cornu-Artis C, Lopez P. 2013;19:169-75. S, Spinardi L, Migliori E, Everolimus versus mycophenolate Banks E, Joshy G, Abhayaratna Humphreys DT Suter CM Farinello D, Sitia G, Harrelson mofetil in heart transplantation: a , . WP, Kritharides L, Macdonald Z, Evans SM, Guidotti LG, randomized, multicenter trial. Am miRspring: a compact standalone PS, Korda RJ, Chalmers JP. Harvey RP, Brendolan A. Nkx2- J Transplant 2013;13:1203-16 research tool for analyzing Erectile Dysfunction Severity as 5(+)islet1(+) mesenchymal miRNA-seq data. Nucleic Acids a Risk Marker for Cardiovascular precursors generate distinct Emmert MY, Wolint P, Wickboldt Res 2013;41:e147. Disease Hospitalisation and All- spleen stromal cell subsets and N, Gemayel G, Weber B, Cause Mortality: A Prospective Huttner IG, Trivedi G, Jacoby participate in restoring stromal Brokopp CE, Boni A, Falk V, Cohort Study. Plos Medicine A, Mann SA, Vandenberg JI, network integrity. Immunity Bosman A, Jaconi ME, Hoerstrup 2013;10:e1001372 Fatkin D. A transgenic zebrafish 2013;38:782-91 SP. Human stem cell-based three-dimensional microtissues model of a human cardiac Bayer SB, Maghzal G, Stocker R, Chan KH, O’Connell R, Sullivan for advanced cardiac cell sodium channel mutation exhibits Hampton MB, Winterbourn CC. D, Hoffmann LS, Rajamani therapies. Biomaterials bradycardia, conduction-system Neutrophil-mediated oxidation K, Whiting M, Donoghoe M, 2013;34:6339-54. abnormalities and early death. J of erythrocyte peroxiredoxin 2 as Vanhala M, Hamer A, Yu B, Mol Cell Cardiol 2013;61:123-32 a potential marker of oxidative Stocker R, Ng MKC, Keech Fang Y, Gupta V, Karra R, stress in inflammation. FASEB J Iismaa SE, Aplin M, Holman A. Plasma total bilirubin levels Holdway JE, Kikuchi K, Poss 2013;27:3315-3322. S, Yiu TW, Jackson K, predict amputation events in KD. Translational profiling of cardiomyocytes identifies an Burchfield JG, Mitchell CJ, Becker M, Borngen K, Nomura type 2 diabetes: the Fenofibrate early Jak1/Stat3 injury response O’Reilly L, Davenport A, T, Battle AR, Marin K, Martinac and Event Lowering in Diabetes required for zebrafish heart Cantley J, Schmitz-Peiffer C, B, Kramer R. Glutamate efflux (FIELD) study. Diabetologia Graham regeneration. Proc Natl Acad Sci Biden TJ, Cooney GJ, mediated by Corynebacterium 2013;56:724-736 RM U S A 2013;110:13416-21. . Glucose Homeostasis glutamicum MscCG, Escherichia Christensen AH, Fatkin D. in Mice Is Transglutaminase coli MscS, and their derivatives. Efficacy of carvedilol in pediatric Ferguson C, Inglis SC, Newton 2 Independent. PLOS ONE Biochim Biophys Acta heart failure. Future Cardiol PJ, Middleton S, Macdonald PS, 2013;8:e63346 2013;1828:1230-1240 2013;9:475-8. Davidson PM. Atrial fibrillation and thromboprophylaxis in heart Kadiiska MB, Basu S, Brot N, Behrens AN, Iacovino M, Lohr Cordina NM, Liew CK, Gell failure: the need for patient- Cooper C, Csallany AS, Davies JL, Ren Y, Zierold C, Harvey RP, DA, Fajer PG, Mackay JP, centered approaches to address MJ, George MM, Murray DM, Kyba M, Garry DJ, Martin CM. Brown LJ. Biochemistry. Effects adherence. Vasc Health Risk Roberts LJ, Shigenaga MK, Sohal Nkx2-5 Mediates Differential Stocker R of calcium binding and the Manag. 2013; 9:3-11 RS, , Van Thiel DH, Cardiac Differentiation Through hypertrophic cardiomyopathy Wiswedel I, Hatch GE, Mason Interaction with Hoxa10. Stem A8V mutation on the dynamic Gavrilov S, Harvey RP, RP. Biomarkers of oxidative Cells Dev 2013;22:2211-2220. equilibrium between closed Papaioannou VE. Lack of stress study V: Ozone exposure genetic interaction between of rats and its effect on lipids, Betihavas V, Newton PJ, Frost and open conformations of the Tbx20 and Tbx3 in early mouse proteins, and DNA in plasma SA, Alexandrou E, Macdonald regulatory N-domain of isolated heart development. PLoS One and urine. Free Radic Biol Med PS, Davidson PM. Importance of cardiac troponin C. Biochemistry 2013;8:e70149. 2013;61:408-415. Predictors of Rehospitalisation in 2013;52:1950-62. Heart Failure: A Survey of Heart Ke Y Ng CA Hunter MJ Costa MW, Guo GL, Wolstein Ghofrani HA, Galiè N, , , , Failure Experts. Heart Lung Circ. Mann SA Heide J Hill AP O, Vale M, Castro ML, Wang Grimminger F, Grünig E, , , , 2013;22:179-83 Vandenberg JI LB, Otway R, Riek P, Cochrane Humbert M, Jing ZC, Keogh . Trafficking AM, Langleben D, Kilama MO, defects in PAS domain mutant Betihavas V Rn Bn Mn, Newton N, Furtado M, Semsarian C, Fritsch A, Neuser D, Rubin Kv11.1 channels: roles of PJ Rn Bn Hons, Frost SA Rn Weintraub RG, Yeoh T, Hayward LJ; PATENT-1 Study Group. reduced domain stability Bn Mph Hons, Macdonald C, Keogh A, Macdonald PS, Riociguat for the treatment of and altered domain-domain PS, Davidson PM Rn. Patient, Feneley M, Graham RM, pulmonary arterial hypertension. interactions. Biochem J provider and system factors Seidman JG, Seidman CE, N Engl J Med 2013;369330-40. 2013:15:69-77. influencing rehospitalisation Rosenthal N, Fatkin D, Harvey in adults with heart failure: RP. Functional Characterization Guner-Ataman B, Paffett- Kwon SC, Yi H, Eichelbaum a literature review. Contemp of a Novel Mutation in NKX2- Lugassy N, Adams MS, Nevis KR, K, Fohr S, Fischer B, You KT, Nurse. 2013;43:244-56 5 Associated With Congenital Jahangiri L, Obregon P, Kikuchi Castello A, Krijgsveld J, Hentze Heart Disease and Adult-Onset K, Poss KD, Burns CE, Burns MW, Kim VN. The RNA-binding Cardiomyopathy. Circ Cardiovasc CG. Zebrafish second heart field protein repertoire of embryonic Genet 2013;6:238-247. development relies on progenitor stem cells Nat. Struct. Mol. Biol specification in anterior lateral 2013;9:1122+. plate mesoderm and nkx2.5 function. Development 2013;140:1353-63. 42 Victor Chang Cardiac Research Institute Lai XN, Beilharz T, Au WC, Muthiah K, Robson D, Ngo T, Nicholas TJ, Chen J, Rain S, Handoko ML, Trip P, Hammet A, Preiss T, Basrai MA, Macdonald PS, Keogh AM, Finch AM, Griffith R. 5-HT1A Gan CT, Westerhof N, Stienen Heierhorst J. Yeast hEST1A/B Kotlyar E, Granger E, Dhital K, receptor pharmacophores to GJ, Paulus WJ, Ottenheijm (SMG5/6)-Like Proteins Spratt P, Jansz P, Hayward CS. screen for off-target activity of CA, Marcus JT, Dorfmüller P, Contribute to Environment- Thrombolysis for Suspected α1-adrenoceptor antagonists. Guignabert C, Humbert M, Sensing Adaptive Gene Intrapump Thrombosis in J Comput Aided Mol Des Macdonald PS, Dos Remedios Expression Responses. G3 Patients With Continuous Flow 2013;27305-19. C, Postmus PE, Saripalli C, (Bethesda) 2013;3:1649-1659. Centrifugal Left Ventricular Hidalgo CG, Granzier HL, Assist Device. Artifical Organs Ohanian M, Humphreys DT, Vonk-Noordegraaf A, van der Lee LK, Bryant KJ, Bouveret 2013;37:313-318 Anderson E, Preiss T, Fatkin Velden J, de Man FS. Right R, Lei PW, Duff AP, Harrop SJ, D. A heterozygous variant in ventricular diastolic impairment Huang EP, Harvey RP, Gelb Muthiah K, Phan J, Robson D, the human cardiac miR-133 in patients with pulmonary MH, Gray PP, Curmi PM, Macdonald PS, Keogh AM, gene, MIR133A2, alters miRNA arterial hypertension. Circulation Cunningham AM, Church WB, Kotlyar E, Granger E, Dhital K, duplex processing and strand 2013;1282016-25. Scott KF. Selective Inhibition Spratt P, Jansz P, Hayward CS. abundance. BMC Genetics of Human Group IIA-secreted Centrifugal Continuous-Flow 2013;14:14-18 Sadrieh A, Mann SA, Subbiah Phospholipase A(2) (hGIIA) Left Ventricular Assist Device RN, Domanski L, Taylor Signaling Reveals Arachidonic in Patients With Hypertrophic O’Neill SM, Liu J, O’Rourke JA, Vandenberg JI, Hill A. Acid Metabolism Is Associated Cardiomyopathy: A Case Series. MF, Khoo SK. The menopausal Quantifying the origins of with Colocalization of hGIIA Asaio Journal 2013;59:183-187 transition does not appear to population variability in cardiac to Vimentin in Rheumatoid accelerate age-related increases electrical activity through Synoviocytes. J Biol Chem Muthiah K, Robson D, in arterial stiffness. Climacteric. sensitivity analysis of the 2013;288:15269-15279. Macdonald PS, Keogh AM, 2013;16:62-9 electrocardiogram. J Physiol Kotlyar E, Granger E, Dhital 2013;591:4207-4222. Li CC, Eaton SA, Young PE, Lee K, Spratt P, Jansz P, Hayward Otton JM, Phan J, Feneley M, M, Shuttleworth R, Humphreys CS. Increased incidence Yu CY, Sammel N, McCrohon Salamonsen RF, Pellegrino V, DT, Grau GE, Combes V, of angiodysplasia of the J. Defining the mid-diastolic Fraser JF, Hayes K, Timms D, Bebawy M, Gong J, Brammah S, gastrointestinal tract and imaging period for cardiac CT Lovell NH, Hayward CS. Exercise Buckland ME, Suter CM. Glioma bleeding in patients with - lessons from tissue Doppler Studies in Patients With Rotary microvesicles carry selectively continuous flow left ventricular echocardiography. BMC Med Blood Pumps: Cause, Effects, packaged coding and non- assist devices (LVADs). Int J Artif Imaging 2013;13:UNSP5. and Implications for Starling-Like coding RNAs which alter gene Organs 2013;36:449-454 Otton JM, Kühl JT, Kofoed Control of Changes in Pump Flow. expression in recipient cells. RNA KF, McCrohon J, Feneley M, Artif Organs 2013;37:695-703. Biol 2013;10:1333-44. Na R, Grulich AE, Meagher NS, McCaughan GW, Keogh AM, Sammel N, Yu CY, Chiribiri A, Samaras K, Viardot A, Lee Li CC, Young PE, Maloney CA, Vajdic CM. De novo Cancer- Nagel E. Four-dimensional image PN, Jenkins A, Botelho NK, Eaton SA, Cowley MJ, Buckland Related Death in Australian Liver processing of myocardial CT Bakopanos A, Lord RV, Hayward ME, Preiss T, Henstridge DC, and Cardiothoracic Transplant perfusion for improved image CS. Reduced arterial stiffness Cooney GJ, Febbraio MA, Recipients. Am J Transplant quality and noise reduction. J after weight loss in obese type Martin DI, Cropley JE, Suter CM. 2013;13:1296-304. Cardiovasc Comput Tomogr 2 diabetes and impaired glucose Maternal obesity and diabetes 2013;7:110-116. tolerance: the role of immune Na R, Grulich AE, Meagher induces latent metabolic defects Paffett-Lugassy N, Singh R, cell activation and insulin and widespread epigenetic NS, McCaughan GW, Keogh resistance. Diab Vasc Dis Res AM, Vajdic CM. Comparison Nevis KR, Guner-Ataman B, changes in isogenic mice. O’Loughlin E, Jahangiri L, 2013;10:40-8. Epigenetics 2013;8:602-11. of de novo cancer incidence in Australian liver, heart and Harvey RP, Burns CG, Burns CE. Samaraweera SE, O’Keefe Li Q, Hakimi P, Liu X, Yu lung transplant recipients. Am J Heart field origin of great vessel LV, van Eyk CL, Lawlor KT, WM, Ye F, Fujioka H, Raza S, Transplant 2013;13:174-83. precursors relies on nkx2.5- Humphreys DT, Suter CM, Shankar E, Tang F, Dunwoodie mediated vasculogenesis. Nat Richards RI. Modeling and SL, Danielpour D, Hoppel CL, Nachtrab G, Kikuchi K, Tornini Cell Biol 2013;15:1362-9 analysis of repeat RNA toxicity VA, Poss KD. Transcriptional Ramírez-Bergeron DL, Qu CK, Perry MD, Ng CA, Vandenberg in Drosophila. Methods Mol Biol Hanson RW, Yang YC. Cited2, components of anteroposterior 2013;1017:173-92. positional information during JI. Pore Helices Play a Dynamic a Transcriptional Modulator Role as Integrators of Domain Protein, Regulates Metabolism in zebrafish fin regeneration. Shen Y, Ward NC, Hodgson Development 2013;140:3754-64 Motion during Kv11.1 Channel JM, Puddey IB, Wang Y, Zhang Murine Embryonic Stem Cells. J Inactivation Gating. J Biol Chem Biol Chem 2013;289:251-263 D, Maghzal G, Stocker R, Croft Nakano H, Liu X, Arshi A, 2013;288:11482-11491 KD. Dietary quercetin attenuates Nakashima Y, van Handel B, Makovey J, Macara M, Chen Perry MD, Wong S, Ng CA, oxidant-induced endothelial JS, Hayward CS, March L, Sasidharan R, Harmon AW, dysfunction and atherosclerosis in Shin JH, Schwartz RJ, Conway Vandenberg JI. Hydrophobic Sambrook PN. High osteoporotic interactions between the apolipoprotein E knockout mice fracture risk and CVD risk co- SJ, Harvey RP, Pashmforoush fed a high-fat diet: a critical role M, Mikkola HK, Nakano A. voltage sensor and pore mediate exist in postmenopausal women. inactivation in Kv11.1 channels. J. for heme oxygenase-1. Free Radic Bone 2013;52:120-125 Haemogenic endocardium Biol Med 2013;65:908-915. contributes to transient definitive Gen. Physiol 2013;142:275-288. Makovey J, Macara M, Chen haematopoiesis. Nat Commun Petrov E, Palanivelu D, Singer J, Trollor JN, Crawford JS, Hayward CS, March L, 2013;4:1564. Constantine M, Rohde PR, J, O’Rourke MF, Baune BT, Seibel MJ, Sambrook PN. Serum Brodaty H, Samaras K, Kochan Ng CA, Ke Y, Perry MD, Tan Cox CD, Nomura T, Minor uric acid plays a protective DL, Martinac B. Patch-Clamp NA, Campbell L, Sachdev role for bone loss in peri- and PS, Hill AP, Vandenberg JI. PS, Smith E. The Association C-Terminal beta 9-Strand Characterization of the MscS-like postmenopausal women: Mechanosensitive Channel from between Pulse Wave Velocity A longitudinal study. Bone of the Cyclic Nucleotide- and Cognitive Function: Binding Homology Domain Silicibacter pomeroyi. Biophys J 2013;52:400-406 2013;104:1426-1434. The Sydney Memory and Stabilizes Activated States Ageing Study. PLOS ONE Méniel V, Song F, Phesse T, of Kv11.1 Channels. PLOS Phan JA, Muthiah K, Robson 2013;8:e61855 Young M, Poetz O, Parry ONE 2013;8:e77032. D, Macdonald PS, Keogh AM, L, Jenkins JR, Williams GT, Kotlyar E, Spratt P, Dhital K, Sobti M, Mabbutt BC. Rational- Dunwoodie SL, Watson A, Ng CA, Torres A, Pages G, based protein engineering: tips Kuchel PW, Vandenberg JI. Granger E, Jansz P, Hayward Clarke AR. Cited1 Deficiency CS. Death on an LVAD-Two and tools. Methods Mol Biol Suppresses Intestinal Insights into hERG K+ channel 2013;996:233-250 structure and function from Sides of a Coin. Heart Lung Circ Tumorigenesis. PLoS Genet 2013;22952-4. 2013;9:e1003638. NMR studies. Eur Biophys 2013;42:71-9

ANNUAL REPORT 2013 43 Sparrow DB, Faqeih EA, Sallout Watson AJ, Gao L, Sun L, Tsun COMMENTARIES REVIEWS B, Alswaid A, Ababneh F, Al- J, Doyle A, Faddy SC, Jabbour Sayed M, Rukban H, Eyaid WM, A, Orr Y, Dhital K, Hicks M, & EDITORIALS Asli NS, Harvey RP. Epithelial Kageyama R, Ellard S, Turnpenny Jansz PC, Macdonald PS. to mesenchymal transition as Fatkin D, Nikolova-Krstevski PD, Dunwoodie SL. Mutation of Enhanced Preservation of Pig a portal to stem cell characters V. Atrial Cardiomyopathy an HES7 in a large extended family Cardiac Allografts by Combining embedded in gene networks. Orphan Disease or Common with spondylocostal dysostosis Erythropoietin With Glyceryl Bioessays. 2013;35:191-200 Disorder? Circulation- and dextrocardia with situs Trinitrate and Zoniporide. Am J Cardiovascular Genetics inversus. Am J Med Genet A Transplant. 2013;13:1676-1687. Chang SW, Davidson 2013;6:5-6. 2013;1612244-2249. PM, Newton PJ, Krum H, Watson AJ, Gao L, Sun L, Salamonson Y, Macdonald PS. Feneley M. Contractility: Still Sparrow DB, McInerney-Leo A, Tsun J, Jabbour A, Qiu MR, What is the methodological Searching After All These Years. Gucev ZS, Gardiner B, Marshall Jansz PC, Hicks M, Macdonald and reporting quality of health JACC Cardiovasc Imaging M, Leo PJ, Chapman DL, Tasic V PS. Enhanced preservation of related quality of life in chronic 2013;6:429-431. Shishko A, Brown MA, Duncan the rat heart after prolonged heart failure clinical trials? Int J EL, Dunwoodie SL. Autosomal hypothermic ischemia with Dunwoodie SL, Hamada H. Cardiol 2013;164:133-140 dominant spondylocostal erythropoietin-supplemented Ways, means and consequences Fatkin D. Familial dilated dysostosis is caused by mutation Celsior solution. J Heart Lung of shaping morphogen gradients cardiomyopathy: current inmri TBX6. Hum Mol Genet Transplant 2013;32:633-640. Editorial overview. Current challenges and future directions. 2013;22:1625-1631. Opinion 2013;23:361-362. Whitty JA, Stewart S, Carrington Global Cardiology Science and Strange G, Gabbay E, Kermeen MJ, Calderone A, Marwick Morrison JL, Lumbers E, Ozanne Practice 2012;8:1-9 F, Williams T, Carrington M, T, Horowitz JD, Krum H, SE, Suter, CM. The Australian Galiè N, Corris PA, Frost A, Stewart S, Keogh AM. Time from Davidson PM, Macdonald PS, Early Origins of Hypertension Girgis RE, Granton J, Jing ZC, symptoms to definitive diagnosis Reid C, Scuffham PA. Patient workshop: a celebration of the Klepetko W, McGoon MD, of idiopathic pulmonary arterial preferences and willingness- scientific contributions made McLaughlin VV, Preston IR, hypertension: The delay study. to-pay for a home or clinical by emeritus Scientia professor Rubin LJ, Sandoval J, Seeger W, Pulm Circ 2013;3:89-94 based program of chronic heart Eugenie R lumbers AM and Keogh AM. Updated treatment failure management: findings professor Caroline McMillen. J. Suter CM, Boffelli D, Martin DI. algorithm of pulmonary arterial from the which? Trail. PloS one Gen. Physiol 2013;4:325-327. A role for epigenetic inheritance 2013;8:e58347. hypertension. J Am Coll Cardiol in modern evolutionary theory? Morrison J.L, Suter CM, 2013;62:D60-72 A comment in response to Zhang B, Day DS, Ho JWK, Botting K.J, Nyengaard J.R. Ng C-A, Pages G, Torres AM, Dickins and Rahman. Proc Biol Song L, Cao J, Christodoulou D, Does maternal obesity change Kuchel PW, Vandenberg JI. Sci 2013;280:20130903 Seidman JG, Crawford GE, Park cardiomyocyte endowment?. Insights into hERG K+ channel PJ, Pu WT. A dynamic H3K27ac Expet Rev Obstet Gynecol Tapson VF, Jing ZC, Xu KF, structure and function from signature identifies VEGFA- 2013;8:1-3. Pan L, Feldman J, Kiely stimulated endothelial enhancers NMR studies. European Journal DG, Kotlyar E, McSwain and requires EP300 activity. O’Rourke MF, Adji A. Guidelines of Biophysics 2013;42:71-79 CS, Laliberte K, Arneson C, on guidelines: focus on isolated Genome Res 2013;23:917-27 Stewart AG, Sobti M, Harvey Rubin LJ; FREEDOM-C2 systolic hypertension in youth. RP, Stock D. Rotary ATPases: Study Team (Keogh AM 2nd Zhang S, Williams-Wyss O, Journal of Hypertension Models, machine elements investigator). Oral treprostinil MacLaughlin SM, Walker SK, 2013;31:649-654. for the treatment of pulmonary Kleemann DO, Suter CM, and technical specification. arterial hypertension in Morrison JL, Molloy L, Cropley Stocker R, Macdonald PS. The Bioarchitecture 2013;3:2-12. patients receiving background JE, Roberts CT, McMillen IC. benefit of coenzyme Q(10) endothelin receptor antagonist Maternal undernutrition during supplements in the management LETTERS TO and phosphodiesterase type the first week after conception of chronic heart failure: a long THE EDITOR 5 inhibitor therapy (the results in decreased expression tale of promise in the continued FREEDOM-C2 study): a of glucocorticoid receptor mRNA absence of clear evidence. Cheruvu C, Huilgol R, Grabs A, randomized controlled trial. in the absence of GR exon American Journal of Clinical Thorburn C, Kuchar D, Walker Chest 2013;144:952-8 1(7) hypermethylation in the Nutrition 2013;97:233-234. B, Subbiah R. Refractory long fetal pituitary in late gestation. QT syndrome and the role of left Tong L, Png E, AiHua H, Yong Vandenberg JI, Conigrave A, DOHaD 2013;4:391-401. King GF, Kirk K. From kinetics cardiac sympathetic denervation. SS, Yeo HL, Riau A, Mendoz E, Intern Med J 2013;43:458-461 Chaurasia SS, Lim CT, Yiu TW, to imaging: an NMR odyssey-a Iismaa SE. Molecular mechanism BOOKS & BOOK festschrift symposium in honour Menache A, Keogh AM. of transglutaminase-2 in CHAPTERS of Philip William Kuchel. Eur Regarding “A process-based corneal epithelial migration and Biophys J. 2013;42:1-2. review of mouse models of Martinac B, Rohde PR, Cranfield adhesion. Biochim Biophys Acta Wang LW, Kotlyar E, Bester L, pulmonary hypertension”. CG, Nomura T. Patch clamp 2013;1833:1304-1315. Feneley M, Omari A, Subbiah Pulm Circ 2013;3:447 electrophysiology for the study RN. Pulmonary arteriovenous Robaei D, Buchholz S, Feneley of bacterial ion channels in giant O’Rourke MF, Adji A. malformation: an unusual cause M. Double Inter-atrial Septum: spheroplasts of E. coli. Methods Misclassification of studies of exertional dyspnoea. Lancet A Rare Cause of Cardioembolic Mol Biol 2013;966:367-80 in ‘Brachial artery tonometry Stroke. Heart Lung Circ 2013;381:1430-1430. and the Popeye phenomenon’ 2012;S1443-9506:01260-7. O’Connell DJ, Ho JWK, Maas Reply. Journal of Hypertension RL. Systems biology of early 2013;31:208-209 Waller A, Girgis A, Davidson tooth development. In Stem PM, Newton PJ, Lecathelinais cells in craniofacial development, C, Macdonald PS, Hayward CS, regeneration and repair (Eds. Currow DC. Facilitating Needs- Huang GT-J and Thesleff I), Based Support and Palliative Wiley, 179-202 Care for People With Chronic Heart Failure: Preliminary Evidence for the Acceptability, Inter-Rater Reliability, and Validity of a Needs Assessment Tool. J Pain Symptom Manage 2013;45:912-925.

44 Victor Chang Cardiac Research Institute Statement of Income and Expenditure

2013 2012

$ $

Income Grants 13,572,060 13,546,412 Fundraising 3,995,479 2,576,593 Bequests 2,004,861 1,586,377 Investment income 1,356,661 1,198,745 Other 129,383 68,968

Total Income 21,058,444 18,977,095

Operating Expenses Salaries and related expenses 13,141,468 11,603,611 Research consumables 2,665,947 1,812,570 Depreciation 2,068,310 2,003,352 Other operational expenses 1,017,218 933,595 Administration expenses 1,910,374 1,900,909 Fundraising expenses1 474,918 489,475

Total Expenses 21,278,235 18,743,512

(Deficit)/Surplus before non operating income (219,791) 233,583 Non Operating income Unrealised gain on investment revaluation to market 1,520,276 983,357

Net Surplus for the year 1,300,485 1,216,940

(1) Fundraising expenses are funded from investment income, so that 100% of donations are used for research

ANNUAL REPORT 2013 45 FUNDRAISING 2013

DIAMONDS ARE FOREVER – To all of our THE VICTOR CHANG HEART TO wonderful friends HEART BALL & MEDIA AWARDS On Saturday, 3 August, the annual Victor Chang and supporters, Heart to Heart Ball raised almost half a million dollars for cardiac research. The theme for the we say thank you. flagship gala dinner, held at The Star Event Centre in Sydney, was ‘Diamonds are Forever’. The Institute exists More than 660 guests in attendance paid tribute to the highly skilled surgeon and humanitarian Dr Victor Chang, because of your whose work has inspired hundreds of researchers. Guests were treated to a throng of colour and entertainment, unwavering support, including a keynote speech from the 2011 Australian of the Year, Mr Simon McKeon AO, silent and live auctions, dinner loyalty and generosity. and dancing. Mr McKeon spoke in depth about his role in chairing the The last 19 years have Federal Government’s independent strategic review of health and medical research in Australia, which has now been possible thanks recommended a ten-year plan for the nation. For the fourth successive year, the Victor Chang Media to your faith in our Awards were also incorporated into the evening’s events. Hotly contested in 2013, Today Tonight Perth reporter Mark work. Gibson was awarded the Victor Chang Award for Excellence in Cardiovascular Journalism (Metropolitan Category). This was the second time Mark has won this award, having won Clockwise from below: the inaugural award in 2010. > Heart to Heart Ball and Media Awards > Chairman, Mr Steven Lowy The winner of The Victor Chang Award for Excellence in > Mr Simon McKeon Cardiovascular Journalism (Regional Category) went to Boel > Today Tonight Perth’s Mark Gibson (centre) Eriksson of the Manly Daily, for her front-page article about celebrity chef Alessandro Pavoni, who has a complex medical history and has suffered two heart attacks. Judges felt the piece both raised general awareness about heart failure, and encouraged direct action from readers in urging them to donate to cardiac research. The Highly Commended Award was won by the Brisbane Courier Mail’s Science & Medical Reporter Janelle Miles, for her story on 40 year-old lawyer Peter Betros who, after falling sick with a flu-like illness that attacked his heart, defied the odds and was kept alive by a mechanical pump until he was able to have a heart transplant.

46 Victor Chang Cardiac Research Institute MONICA O’LOUGHLIN WOMEN AGAINST HEART DISEASE LUNCH In 2012, the Victor Chang Cardiac Research Institute held its inaugural lunch in honour of our former finance manager and friend, the late Monica O’Loughlin, who died from a heart attack aged just 51.

The event aims to increase awareness of heart disease amongst women, with the disease killing four times as many women in Australia than breast cancer every year. The keynote speaker at 2013’s event was Dr Noel Bairey Merz, Director of the Barbra Streisand Women’s Heart Centre and Cedars Sinai Heart Institute in the United States. Dr Merz has an extensive publication record of over 180 scientific publications, 200 abstracts and numerous book chapters. She explained to the 400 female attendees that as a society we have been programmed to think of heart disease in a ‘typically male way’. This is despite the fact that only one third of women will experience the same symptoms as a male when suffering a heart attack. Our sincere thanks go to Dr Merz, Commonwealth Bank Women in Focus for co-hosting, producer Ken Laing, and emcee Janine Perrett.

Top right: Dr Bairey Merz with Bob Graham Right: Dr Noel Bairey Merz

ANNUAL REPORT 2013 47 CHAIN REACTION – THE ULTIMATE CORPORATE CYCLING CHALLENGE In 2007, Berrick Wilson, a Partner at Korda Mentha and National Head of Real Estate Advisory, founded Chain Reaction.

The non-mass participation cycling event was established as an The 2013 New South Wales leg of Chain Reaction raised money act of gratitude for the care and attention Berrick’s family received for the Institute’s Embryology Laboratory, headed by Professor when his two-year-old daughter Milla was rushed to hospital with Sally Dunwoodie, and covered a staggering 1175km from a brain haemorrhage. His experience over the weeks he and his Melbourne to Sydney. wife spent at Monash Medical Centre made him realise that more 29-intrepid riders passed through towns including Beechworth, could be done to help sick children. Corryong, Cooma, Canberra and Moss Vale, as well as covering Chain Reaction invites individuals who want a physical challenge the picturesque and challenging Snowy Mountains with a visit to to participate in a gruelling 1000 km plus ride over seven days. Cabramurra, Australia’s highest town. In return, participants benefit from both valuable networking The 2013 event sponsors were Westpac, Gadens Lawyers, Ernst opportunities, and the immense satisfaction of directly helping & Young, Westfield, Brookfield Mulitplex, National Australia Bank sick children in need. and Colonial First State. Chain Reaction also challenges riders to use their standing in the business community to draw on the support of their networks, to raise a pre-determined amount in personal donations. The riders participate in the spirit of camaraderie, teamwork and fun, with each event completed as a group and not as a race.

48 Victor Chang Cardiac Research Institute YOUNG APPEALS COMMITTEE OUR HEARTFELT THANKS ALSO TO: LAUNCHED > Richard Becker, and the Becker Film Group for supporting the In September, the ‘Young at Heart’ launch event Institute through the Australian release of the movie ‘Diana’ marked the establishment of the Young Appeals > Prue Macsween, who competed fiercely on behalf of the Institute in Celebrity Apprentice Committee. > Michael Renford and Randwick City Council, for hosting the Chaired by Marcus Chang, Dr Victor Chang’s youngest son, annual Des Renford Gala Day fundraiser, and for working with the Committee formed to help engage younger audiences with Sydney Airport Corporation to enable the Institute to sell pens the Institute’s work. in the departure lounge – a new initiative in 2013 > Kate & Diana Ritchie, for their phenomenal feat in swimming Around 200 guests were invited to have their heart health the Dardanelle Straight checked in the Victor Chang Health Check Booth, talk face to face with scientists, and speak with fitness experts about their > Club Marconi for hosting another successful ‘Heart of the exercise regime. West’ ball in Western Sydney; > Cameron Irving for hosting ‘Crabfest’ – the fun and fast paced Prue Macsween, star of 2013’s Celebrity Apprentice, emceed crab eating competition the event and guest speaker was 17-year-old Joel Seeto who > The Westfield Group for hosting the 2013 Golf Day at has hypertrophic cardiomyopathy (a disease of the heart muscle St Michaels Golf Course, Little Bay where the wall becomes thickened making it harder for the heart > The supporters of our annual ‘Trivia at the Chang’ quiz night to pump blood around the body). > Our many other very generous friends and supporters ‘Young at Heart’ raised over $10,000, which will be used to help throughout 2013. fund a new ‘Victor Chang PhD scholarship’ being offered in 2014. Below: Professor Sally Dunwoodie gave a speech at the Australian Below: Joel Seeto (left) with Marcus Chang premiere of ‘Diana’ in September 2013

ANNUAL REPORT 2013 49 Community Outreach 2013

KEEPING AUSTRALIAN HEARTS PUMPING: THE VICTOR CHANG HEALTH CHECK BOOTH The Victor Chang Health Check Booth travels the length and breadth of the nation, testing Australians for key heart disease risk factors by checking their blood pressure, blood cholesterol and blood glucose levels. Staffed by New South Wales-trained nurses, 2013 was a milestone To book the Victor Chang Health Check Booth for your next year for the Booth, which tested its 15,000th participant in corporate or public event, please contact Jayne Baric on Parramatta, Western Sydney, and visited almost 70 other locations (02) 9295 8760 or [email protected]. across four states. The Health Check Booth is generously supported by HCF, Kia Motors, IMB Community Foundation and Sydney Markets Foundation.

THE BOOTH BY NUMBERS IN 2013

146 4 9148 States and many NSW Testing days across regional locations Individual tests Australia visited carried out

63 144 2557 529 Or 29% had one or more Average number of Record number of individuals results outside of ideal Or 6% of participants people tested tested in one day range, recommended had high blood per day to visit GP pressure

4843 2013 631 Participants did not know Or 23% had high Had high glucose/ their cholesterol levels cholesterol blood sugar levels

50 Victor Chang Cardiac Research Institute SCHOOL SCIENCE AWARDS HONOUR VANESSA CHANG INDUCTS STUDENTS SCIENTIFIC BRIGHT SPARKS TO ‘CHANG HOUSE’ This year officially marked the tenth anniversary In December, Vanessa Chang was invited to of the Victor Chang School Science Awards, speak about her father’s life and launch ‘Chang which were developed to encourage a passion House’ at Sydenham Catholic Regional College for science amongst secondary school students, in West Melbourne. and inspire them to consider a career in the field. Vanessa welcomed incoming year 11 students, and inducted More than 200 awards were handed out to Year 11 students at them into the new school house set up in honour of Dr Victor ceremonies across the Greater Sydney region, in Campbelltown, Chang, with the core values of dignity, compassion and Penrith, Blacktown and Wollongong. endeavour. The award winners are nominated by their schools for Victor was selected by students to sit amongst other eminent demonstrating an outstanding commitment to their scientific Australians as a house patron. Vanessa said she was delighted studies throughout the year. They are presented with a framed to address the large group of assembled students, and to give certificate, and invited to visit the Institute. them a very personal introduction. The young winners are bucking trends, with a 2011 report from Below: Vanessa Chang (9th left) with members of ‘Chang House’ at Sydnenham Catholic Regional College the Department of Education, Employment and Workplace Relations showing that 94 per cent of Year 11 and 12 students were enrolled in science subjects 20 years ago, compared with just 51 per cent in 2010. Below: Wollongong School Science Award recipient Kalidevi Samuels-Connell (centre) with Bob Graham and Mrs Ann Chang

ANNUAL REPORT 2013 51 The tonality, light and composition are tender, and perfectly fit the theme of the heart.

ART OF THE HEART 2013: VICTOR CHANG SCIENCE IMAGE COMPETITION In 2013, the Institute held the ‘Art of the Heart’ science image competition, which encouraged research staff to submit pictures of their work that they believe demonstrate the beauty of science. The competition was judged by professional Sydney-based artist Giles Alexander, who trained at the world-renowned Central St. Martins College of Art & Design in London and displays his work at the Martin Browne Contemporary Gallery in Paddington. A plethora of talented scientists from across the Institute submitted their images – with two runners up and an overall winner’s prize awarded.

WINNER: Alexis Bosman (Harvey Laboratory) From humble cell beginnings come hearty complexities: This heart shaped cluster of microscopic cells 400x magnified was created using induced pluripotent stem cells – a specialised type of stem cell which originally began as skin cells. After the process of reprogramming, the cells aquire the capability of forming any cell type in the body, including cells of the heart. Under special conditions, these cells can be coaxed into producing cardiomyocytes – heart muscle cells – which beat like native heart tissue. Judge comments: The beautiful clarity of the shot captured the familiarity of the heart, and the image crosses the line between the human and the scientific. The tonality, light and composition are tender, and perfectly fit the theme of the heart.

52 Victor Chang Cardiac Research Institute RUNNER UP: RUNNER UP: HIGHLY COMMENDED: HIGHLY COMMENDED: Elvira Forte and Nasim Mohammadi Maryrose Constantine Julie Moreau Vaibhao Janbandhu (Lee Laboratory) (Martinac Laboratory) (Dunwoodie Laboratory) (Harvey Laboratory) The white heart: An edited The last sunset heart: As a Heart of the placenta: Brush strokes: Adult cardiac microscopic visualisation, control for an experiment, A mother gives more than stem cells differentiate into 72 hours post fertilisation the heart of a sham surgery just love to her child during smooth muscle cell lineage of a zebrafish’s embryo. mouse was harvested. The pregnancy. Through the when cultured in hypoxia heart was then cryosectioned, placenta, she also provides Judge comments: This is and exposed to transforming fixed and stained for proteins, food and oxygen to help her a cool, objective and bold growth factor. Confocal which play a role in cardiac child grow. If the placenta image, the zebrafish can be images show differentiated conduction disease. Lastly, does not form properly, then made out perfectly and it cardiac stem cells, which the image of the whole the embryo will not grow truly describes the creature, stained show muscle action heart was pieced together by properly, and may even die particularly the heart. The (red), calponin (green) and tiling multiple z-stack images before birth. This 4000x choice of title is wonderful. DNA (blue). acquired at 10x magnification magnified image shows a using a confocal microscope. mouse placenta that has not Judge comments: There The gradient distribution formed correctly. The blood is a great use of colour in of the fluorophores across vessels of the embryo are this image, which captures the heart bears a striking shown in bright red, with a sense of realism and resemblance to a sunset. supporting cells shown in abstraction. The very high blue and cyan. magnification represents Judge comments: This is a the ‘other worldliness’ of very strong image, which Judge comments: Love this technology, and the window seems to go on forever. It image. Has a strong familial technology affords us. The would have great animation element to it, which will blue centre is suggestive of potential. resonate with many. an eye – and a real life or entity.

ANNUAL REPORT 2013 53 Corporate Supporters Our thanks go to the following organisations who continue to support our work each year. You too can help us in our fight against heart disease. Support the Victor Chang Cardiac Research Institute by calling 1300 VICTOR (842867), or visit www.victorchang.edu.au THE VICTOR CHANG CARDIAC RESEARCH INSTITUTE Lowy Packer Building 405 Liverpool Street Darlinghurst, NSW, Australia 2010 Phone: (02) 9295 8600 – 1300 842 867 International Phone: +61 2 9295 8600 Fax: (02) 9295 8601 International Fax: +61 2 9295 8601 www.victorchang.edu.au ABN 61 068 363 235

OUR MISSION The relief of pain and suffering and the promotion of well-being, through an understanding of the fundamental mechanisms of cardiovascular biology Proudly printed by Blue Star Group in health and disease. Design: Pro Bono Publico Victor Chang Cardiac Research Institute Photography: Peter Morris, Karl Schwerdtfeger & Djordje Djordjevic 2013 Annual Report ANNUAL REPORT 2013 ART OF THE HEART 2013 Annual Report 2013 From humble cell beginnings come hearty complexities – winning entry from Alexis Bosman, Developmental & Stem Cell Biology Division This heart shaped cluster of cells 400x magnified was created using induced pluripotent stem cells, a specialised type of stem cell which originally began as skin cells. After ‘reprogramming’, the cells have the ability to form any cell type of the body, including cells of the heart. Under special conditions, these cells can be coaxed into producing heart muscle cells (cardiomyocytes).

VICTOR CHANG CARDIAC RESEARCH INSTITUTE Bringing research to life