Garvan Institute of Medical Research Annual Report 2009 Contents ......

Who we are, What we do 03 Garvan's mission is to make significant Reports contributions to medical research that will Chairman's Report 04 Executive Director's Report 06 change the directions of science and medicine Garvan Research Foundation Chairman's Report 08 and have major impacts on human health. Garvan at a Glance Research Collaborations 11 Garvan strives to enhance and develop research Patent Portfolio by Category 12 Scientific Publications 12 programs that combine fundamental science Philanthropic Support 12 Staff Profile 13 with strong clinical interactions. Operating Income 13 Peer Reviewed Grant Income 13 Organisation Chart 15

Research Highlights 17

Research Programs & Initiatives Cancer Program 18 The Kinghorn Cancer Centre 26 Diabetes & Obesity Program 28 Diabetes Vaccine Development Centre 34 Immunology Program 36 Neuroscience Program 44 Osteoporosis & Bone Biology Program 48

Core Research Facilities 53

Management Highlights 55

Business Development 57

Garvan Community Life Governors 58 Partners for the Future 58 Volunteers 58 Garvan Supporters 59 Bequests 61

Governance Institute Governance 63 Foundation Governance 66

Publications 71

Financial Highlights Income Statement 81 Balance Sheet 82 Garvan Research Foundation Statement of Funds 83 Who we are, What we do ...... 03

The Garvan Institute of Medical Research is a world leader in its field, pioneering study into some of the most widespread diseases affecting our community today. Research at Garvan is focused upon understanding the role of genes in health and disease as the basis for developing future cures.

Significant breakthroughs have been achieved by Garvan scientists in the understanding and treatment of diseases such as:

_ Cancer _ Diabetes and obesity _ Alzheimer's and Parkinson's disease _ Osteoporosis _ Arthritis and asthma _ Pituitary disorders

Garvan's ultimate goal is prevention and cure of these major diseases. Chairman’s Report CHAIRMAN’S REPORT ...... 05

2009 We were particularly pleased to name the Centre The Kinghorn Cancer Centre: a joint facility of the Garvan Institute of Medical Research and St Vincent's Hospital I am pleased to report that Garvan continued its excellent record of research in recognition of a most generous donation of $25m from the Kinghorn Foundation. success in 2009, as measured by grants, publication impacts and international awards, and we are justly proud of our faculty and staff. Business Development Garvan's success in basic research continues to be matched by progress in Several important strategic initiatives were consolidated during the year, including: translating research “discoveries” into real outcomes for patients. _ Planning approval and funding for the new Garvan St Vincent's Cancer Centre _ Implementation of all the major recommendations arising from the Strategic 2009 saw excellent progress in several collaborations with the biotech industry. Review of the Institute completed by the international panel, and Positive early results were generated from the research collaboration with US west _ A highly successful first year of operations for Australian BioResources, our coast biotech, Kai Pharmaceuticals, to develop a potential Type 2 diabetes major breeding and holding facility for experimental mouse models in the therapeutic. This project is testing a molecule that may be effective in blocking Southern Highlands. "PKC epsilon" (PKCe), an enzyme that is active during diabetes and which reduces the availability of insulin. Financial Performance Garvan's operating income grew to approximately $64m in 2009 from $46m the Similarly the licence to Danish-based NsGene A/S of the hormone galanin which is previous year, an increase that is testament to the quality of Garvan research. being developed as an epilepsy therapy continued its progression towards phase 1 Philanthropic support through the Garvan Research Foundation, essential for clinical trials. Other exciting collaborations are detailed in this Annual Report. providing critical equipment and facilitating new initiatives, continued to be strong, with over $5.3m in general and specific grants contributed to research programs 2010 and almost $6.4m into the long term endowment of the Institute. Australia wide, medical research can proudly boast its continuing discovery record in Our People causes of, and potential cures for, many of the world's diseases. I take this opportunity Garvan has been very well served for many years by the commitment and counsel to add Garvan's thanks and congratulations to the extraordinary efforts of Elizabeth of an outstanding Board of Directors. There were several Board changes during Blackburn, Australia's most recent addition to its long list of Noble laureates. 2009 as longstanding members Graham Bradley and Professor Ron Trent resigned to be replaced by the incoming Chair of the Foundation, Geoff Dixon, and Dr John Given this performance, it is especially disappointing once again to be obliged to Horvath. During Graham Bradley's time as Chair of the Foundation for the past observe the appalling lack of funds in this State and in this country for the operating decade, the Endowment Fund grew from ~$4m to nearly $28m. We also welcomed support (often referred to as infrastructure funding) necessary to run the Anne Keating and Jillian Segal as nominees of the NSW Government and the laboratories. Scientists in universities and medical research institutes depend on University of New South Wales (UNSW) respectively. The Institute is most grateful success in the NHMRC research grants scheme for their salaries. But for every dollar for the contributions made by the outgoing directors. Lisa McIntyre, Chair of our of such grants we need about another 70c for day to day lab and Institute Business Development Advisory Council, and Peter Smith, Dean of Medicine at operating expenses. We, like all others in research, are currently relying on past UNSW, were both reappointed for a further term. I was also honoured to be endowments and current donations to find this 70c to keep the doors open. This is reappointed as a nominee of the Trustees of St Vincent's Hospital. not a long term solution for Garvan or the research platform of this nation.

Garvan St Vincent's Cancer Centre The Board is confident that, with the support of government and the community, The mission of our Centre is to create a facility of international standing and best our research will continue to have a growing impact on human health, particularly as practice in translational cancer research which will accelerate the rate at which new we integrate it even more closely with health care delivery. discoveries can be trialled in the clinic. Once again my sincere thanks and admiration are extended to Professor John Shine, 2009 witnessed extraordinary and exciting progress for the Garvan St Vincent's his senior management team, faculty and staff. Cancer Centre. The architects (Bligh Voller Nield) completed the design work based on our detailed functional and design briefs and development approval was finally granted in late December. Importantly, we also received a $70m grant from the Federal Government's Health and Hospitals Fund and a $2.5m grant from the Australian Cancer Research Foundation; we also accumulated philanthropic support of nearly $40m plus the commitment of the land from the Trustees of St Vincent's Hospital. Together with the funds raised from the inspiring “Nuns Run” and the St Vincent's Garvan Gala Dinner, we were able to reach our goal of $110m needed for Bill Ferris AC the construction and fit-out of this important and innovative facility. The Centre Chairman should be ready for occupancy by early 2012. Garvan Institute of Medical Research Executive Director’s Report EXECUTIVE DIRECTOR’S REPORT ...... 07

2009 Australian BioResources (ABR) The state-of-the-art holding and breeding facility for experimental mouse lines at 2009 was another very productive year for Garvan in terms of significant research Moss Vale provides critical infrastructure for Australian innovation. The facility findings, success in obtaining competitive grants and growth in the number of completed its first full year of operation in 2009, reaching 50% of total capacity papers accepted for publication in prestigious international journals. We published (approximately 25,000 mice). It now holds all major breeding colonies for Garvan 176 peer reviewed research papers, the top 80% in journals with an average impact and 7 partner institutes. factor of 9.2. This remains above internationally accepted benchmark levels and is testament to the excellence and commitment of our researchers. Strategic Review During 2009 the final recommendations of the international review were Research publication productivity was matched by success in applications for implemented. The smaller research units of autoimmunity and pituitary research competitive grants. Our funding from the National Health and Medical Research were integrated into the Immunology and Neuroscience Programs respectively. A Council (NHMRC) rose to a record $19.1m, up from $18.7m in 2008. Overall, peer Scientific Advisory Council of eminent international and national researchers was reviewed grant funding increased to approximately $30.2m. formally established and will hold its inaugural meeting in October, 2010. The Council will help advise the Institute on current and future research directions. Of particular importance was Garvan's role as a lead partner in the pancreatic cancer arm of the International Cancer Genome Consortium. The Consortium brings Campus Developments together the world's leading scientists, through 11 funding organisations in 8 An active member of the St Vincent's Campus, Garvan values its historic and countries, and aims to catalogue the genetic changes of the 50 most common ongoing close association with St Vincent's Hospital and its commitment to the cancer types. values of the Sisters of Charity.

The Australian team will be led by Professor Andrew Biankin from Garvan and Our joint venture with St Vincents & Mater Health Sydney to establish a Garvan St Professor Sean Grimmond from the University of Queensland's Institute for Vincent's Cancer Centre, made exceptional progress in 2009 and is detailed Molecular Bioscience in Brisbane. It also involves collaborative contributions from elsewhere in this report. As part of the demolition of existing buildings during the Walter and Eliza Hall Institute of Medical Research in Melbourne, Johns Hopkins construction of the Cancer Centre, the St Vincent's Hospital Diabetes Centre is University in Maryland, the Ontario Institute for Cancer Research and the University being temporarily housed in the Garvan building. This provides the opportunity for of California, San Francisco. us to explore even more effective ways of translating the findings of diabetes and obesity research into improved patient outcomes. Garvan has also played a leadership role in the International Human Epigenome Consortium (IHEC). Professor Susan Clark, Head of our Epigenetics Group, was a 2010 founding member of the small National Institutes of Health USA (NIH) funded task force that initiated the project. This new initiative to map the epigenetic The upcoming years promise much for Garvan, with the addition of approximately modifications of the human genome was officially launched in Paris in January, with 250 new researchers in the Cancer Centre, expansion of our Neuroscience, Immunology Professor Clark on the interim steering committee. and Diabetes and Obesity Programs, and consolidation of the long-running translational research activities emanating from the Osteoporosis Study based in Staff numbers across the organisation grew to a total of 504. Growth was Dubbo. Such expansion places extra pressure on our already minimal infrastructure particularly strong in our Cancer, Immunology and Diabetes and Obesity Programs, resources - a challenge that the Board and staff are committed to overcoming. reflecting ongoing success in competitive grant applications for new and existing projects. After nearly a decade at Garvan, two of the Institute's leading immunology During 2010 we will remain clearly focused on elucidating the fundamental basis of groups, led by Professors Charles and Fabienne Mackay, relocated their research to disease. We will also drive the translation of our research discoveries into new and Monash University in Melbourne. Although their direct input into Garvan research improved ways to prevent and treat the major diseases that challenge our society. will be missed, they will retain honorary appointments at Garvan and continue their strong collaborative research activities with several Garvan groups. Following an international search, we were very fortunate to appoint Dr Robert Brink as the new Immunology Program Leader. Dr Brink brings exceptional skills and a universally respected reputation to the role, which will increasingly focus on a closer integration of immunology across the spectrum of Garvan research programs. John Shine AO FAA Executive Director Garvan Institute of Medical Research Chairman’s Report CHAIRMAN’S REPORT GARVAN RESEARCH FOUNDATION ...... Garvan Research Foundation 09

After taking over the Chair in April, I am very pleased to report that the Foundation's Planning, administration and risk management of the Nuns' Run took up many of the results have surpassed budgeted expectations for 2009 with a total income of Foundation's resources during the busiest time of our year and peak period for $13.6m. This marks a fourth consecutive year of growth for the Foundation and is donations. The team deserves to be congratulated on their multi-tasking ability, a testament to the fact that the combination of a loyal community of informed fitting complement to the Sisters' fortitude. The final fun run in Centennial Park was donors, a premium brand and a dedicated team can, together, surmount even a greatly enjoyed by staff of both the Garvan and St Vincent's and their dogs, and a global financial crisis. We are deeply indebted to our supporters and our staff for this total of over $200,000 raised towards the Cancer Centre. result and proud of the contribution we have therefore been able to make to Garvan's science. Board and staff movements I wish to take this opportunity to thank my fellow Directors for the welcome offered Gift income to me as incoming Chairman and for the support they offer to the Foundation. We are especially indebted to a wonderful Garvan supporter by the name of Margaret Benning, who sadly passed away in 2008 and wanted her estate deployed I would especially like to highlight the exceptional service provided by Mr Graham to further our research into better methods of diagnosis, prognosis and treatment Bradley AM over a term of ten years as Foundation Chairman from 1999 to 2009. of most of the major diseases affecting our society today. This thoughtful bequest Mr Bradley oversaw and encouraged much forward progress during this period has brought the Foundation's bequest income for 2009 to a total of $7.8m, which thanks to his dedication to the philanthropic cause. His stature as a Director and will grow the Institute's reserves in the endowment fund maintained to address Chair and his corporate expertise have been recently recognized by his appointment special needs or emergencies and foster new directions. Additional gifts totalling as President of the Business Council of Australia. $5.8m were generously donated, mostly by individual supporters, and we thank each and every one of them. I also acknowledge the contribution as a Director made by Mr Alexander Brennan (2000-2009); Mr John Koch (2000-2009); and Ms Meredith Hellicar (2002- Capital campaign 2009). It is also my pleasure to have welcomed to the Board this year In a challenging economic climate, the Foundation also carried responsibility for Mr Simon Mordant. fundraising for our capital project, the Garvan St Vincent's Cancer Centre. A number of supporters have helped us reach the campaign goal, but none more so than the I am pleased to report that the Foundation team's membership has remained stable Kinghorn Foundation. Following an initial gift made in 2008, John and Jill Kinghorn in 2009, with the addition of two new fundraising positions (Ms Gabriella Lang committed an extraordinary gift of a further $20m to the Centre. This is an joined in January, and Ms Georgie Le Poer Trench in September) as a necessary example of the type of transformative philanthropy we see only seldom in Australia, response to the additional responsibility of the Cancer Centre. I also welcome Ms and it is hard to express our gratitude adequately. Lynell Riley, who started as Assistant to the CEO in November.

Events I am impressed with the efficiency of Foundation operations and proud to say that The Foundation's activity levels were at an all-time high in May and June this year all Garvan donors can have absolute confidence in the leadership of our CEO and due to the inaugural Nuns' Run. This was a daring, creative and multi-faceted event the determination of her team to achieve maximum support for Garvan's science which involved 11 Sisters of Charity walking 400 km from Dubbo to Darlinghurst to coupled with well-controlled expenditure. raise funds for the Cancer Centre. Along the way, the Sisters engaged in high teas and dinners, memorial services and even a drumming circle with regional communities I look forward to getting to know our supporters in the year ahead and to playing who supported their endeavours to the hilt. Ms Delta Goodrem, Patron of the Centre, my part in what I fully believe will be the bright future of the Foundation and the attended both the start event in Dubbo and the finale in Sydney. Garvan Institute.

A number of sponsors contributed most generously to make the event possible: for example, the essential support vehicles were donated by Citroen Australia. I would particularly like to thank M & C Saatchi for their generous provision of in-kind support for the Nuns' Run and development of the larrikin and eye-catching logo.

Geoff Dixon Chairman Garvan Research Foundation Garvan at a Glance ...... 11

Research Collaborations GARVAN AT A GLANCE GARVAN AT A GLANCE ...... 12 13

Patent Portfolio by Category 550 Staff Profile

504 440 488 Number of Staff Portfolio Percentage Number of Patents 433 Staff Breakdown 2008 2009 Demographics 403 Therapeutics 4% 1 330 373 Researchers 314 296 _ Average age 37 Students 68 87 _ Researchers from 55 countries Drug discovery tools 11% 3 308 220 Scientific Facility Staff 62 68 _ Research Staff 37.75% male, New treatments 19% 5 Secretarial & Admin 35 39 62.25% female Diagnostics 30% 8 110 Foundation 7 11 Therapeutic target 36% 10 DVDC 2 3 0 2004 2005 2006 2007 2008 2009 Total 488 504

200 Scientific Publications Operating Income

175 185 176 150 Impact factor of scientific publications 2009 $64 Million One of the major challenges facing 151 153 Number of Publications Number of 125 Each paper published constitutes a new piece of knowledge, and scientists successful research institutes 135 Peer reviewed grants 47% aim to publish in the most highly regarded journal in their area of research. around Australia remains the “gap” 115 100 Each journal has an “impact factor” which is a common measure of its Other grants 26% between the total costs of doing 75 relative importance within a specific discipline. Research organisations use research and the funding provided Donations 8% “average impact factor” measurements to determine the overall significance by competitive research grants. For 50 of their research output. For example, in 2009 Garvan achieved an “average NSW Government 6% every dollar of research funding 25 impact factor” of 9.2 for the top 80% of its publications. This is a very awarded, another 70 cents is Industry partners 1% respectable tally, well above the international benchmark. required to carry out the research. 0 2004 2005 2006 2007 2008 2009 Other income 12%

Philanthropic Support Peer Reviewed Grant Income

8 30 Total Income Donations are particularly important in $ Mil $ Mil 7 (excluding bequests) received two respects: Year NHMRC Other Income $ mil Income Income $ mil Income by Garvan Research Foundation 24 6 _ They provide seed funding for novel 2004 9,244 6,222

5 $3,539,000 work, which may not attract other 18 2005 12,080 8,685 support for several years 4 $2,790,000 2006 13,832 8,184 _ They fund core items of equipment 12 3 $4,158,000 that are typically not covered by 2007 16,682 8,530 2 $5,370,000 research grants 6 2008 18,695 9,159 1 $6,966,000 2009 19,094 11,061 0 $5,806,000 0 2004 2005 2006 2007 2008 2009 2004 2005 2006 2007 2008 2009 Organisation Chart Garvan Institute of Medical Research Board of Directors Garvan Research Foundation Chairman Mr Bill Ferris AC Board of Directors

Chairman Mr Graham Bradley AM (until 28.4.09) Executive Director Prof John Shine AO FAA Chairman Mr Geoff Dixon (from 28.4.09)

Development & Support Group Cancer Garvan Research Foundation

Chief Operating Officer Mr John Dakin Leader Prof Rob Sutherland FAA Chief Exec Officer Ms Carole Renouf Senior Scientists Australian BioResources Prof Susan Clark Dr Jenny Kingham Prof Roger Daly A/Prof Sue Henshall Business Development & Legal Affairs Dr Maija Kohonen-Corish Ms Christina Hardy Prof Liz Musgrove Corporate Services A/Prof Chris Ormandy Ms Cate Smith Cancer Development Laboratory Finance and Accounting Prof Marie Dziadek Ms Cherry Dutton Human Resources Board Committees Diabetes & Obesity Ms Deborah Pearson _ Business Development Advisory Information Technology Leader Prof David James FAA _ Finance & Audit Mr Jim McBride Senior Scientists _ Investment _ Remuneration Operations A/Prof Trevor Biden Mr David Keenan Prof Lesley Campbell AM Institute Committees Science Communications Prof Don Chisholm AO _ Executive Research Ms Alison Heather A/Prof Greg Cooney _ Appointments & Promotions A/Prof Antony Cooper _ Scientific Advisory Council Prof Ted Kraegen _ BTF Policy Advisory Dr Ross Laybutt Diabetes Vaccine Development Centre _ Higher Degrees A/Prof Katherine Samaras _ Information Technology Chief Exec Officer Ms Rowena Tucker Dr Carsten Schmitz-Peiffer _ OH&S Consultation _ Operations Advisory _ Seminar Program Core Research Facilities Immunology _ Common Users of Building Equipment Australian BioResources (CUBE) Leader Prof Antony Basten AO FAA (acting Peter Wills Bioinformatics Centre until 31.12.09) Pieter Huveneers Molecular Imaging Unit Leader Dr Robert Brink (from 1.1.10) St Vincent’s Research Precinct (SVRP) Gene Chip Facility Committees Biological Testing Facility Senior Scientists _ Animal Ethics Clinical Research Facility Dr Shane Grey _ Human Research Ethics MLC Community Foundation Flow Facility Dr Jenny Gunton _ Institutional Biosafety Australian Cancer Research Foundation Dr Cecile King _ SVRP Management _ SVRP OH&S Unit for the Molecular Genetics of Cancer Prof Jonathan Sprent FRS FAA Dr Stuart Tangye Garvan is a partner in the CRCs for Asthma and Biomedical Imaging Development. Garvan is a shareholder in the spin-out Neuroscience company G2 Therapies Ltd. Leader Prof Herbert Herzog Senior Scientists Dr Sharon Oleskevich A/Prof Amanda Sainsbury-Salis Dr Bryce Vissel Pituitary Research Unit Prof Ken Ho

Osteoporosis & Bone Biology

Leader Prof John Eisman AO Senior Scientists Prof Tuan Nguyen Dr Paul Baldock Research Highlights ...... 17

_ Discovered a promising therapeutic _ Found that fats disrupt movement of _ Demonstrated that a tiny genetic target for prevention of Type 1 protein out of the cellular protein-folding irregularity in the gene encoding for diabetes, a molecule known as BCMA, compartment in pancreatic insulin- the growth factor IL-21 greatly which effectively subdues the immune producing cells, triggering cell death. boosts its expression, leading to the cells that cause the disease. development of Type 1 diabetes in _ Showed that the three signalling mice. The absence of the irregularity, _ Extended our prognostic models for molecules, TRAF2, TRAF3 and cIAP, on the other hand, keeps IL-21 at predicting fracture risk for men and function together to control B cell normal levels and prevents women, implemented in survival and are all potential B cell development of the disease. www.fractureriskcalculator.com, tumour suppressors, so they may widely used by doctors and patients prevent development of cancer in _ Proved that inflammation in the brain worldwide. these cells. prevents stem cell proliferation and neural repair, a finding that will have _ Found that sex hormones and the _ Identified the specific neuronal important therapeutic implications for neurotransmitter neuropeptide Y pathways in the brain that respond to Parkinson’s and Alzheimer’s disease. (NPY) work together to control fat pancreatic polypeptides and reduce levels and bone density in the body. appetite. This highlights a potential _ Demonstrated that ‘short chain fatty new way of treating obesity. acids’ (the by-products of bacterial _ Used new protein technology to fermentation of insoluble dietary fibre identify that a specific group of cell _ Reported findings of initial clinical studies in the gut) bind to GPR43, a molecule signalling proteins, Src family kinases, with a novel treatment that reduces expressed by immune cells that acts represent potential therapeutic targets bone breakdown, and which has major as an anti-inflammatory receptor. in basal breast cancer, an aggressive potential in osteoporosis treatment. sub-type of breast cancer. _ Characterised a new 5 biomarker _ Showed that different forms of the panel that predicts outcome in early _ Showed new ways of artificially PKC enzyme family cause insulin breast cancer. boosting the numbers of a certain resistance in different ways, raising class of immune cells (regulatory T the potential for combination therapy. _ Showed that NPY receptors in the cells), a process which could be used body, rather than the brain, regulate to prevent the rejection of organ _ Demonstrated that neurotransmitters fat burning and storage, and that transplants or the development of in the brain play a critical role in the blocking them can prevent fat gain. autoimmune diseases. regulation of bone mass, a function that has been considered purely _ Identified that the oncogenic signalling _ Identified new serum biomarkers for mechanical. Specifically, neuropeptide protein Gab2 plays an important role therapeutic response to the Y (NPY) directly controls the cells that in early breast cancer development. chemotherapy drug docetaxel in make bone, increasing bone mass in advanced prostate cancer. line with body weight. _ Showed that SERMs, a class of synthetic oestrogens commonly used _ Showed that over-eating generates _ Advanced candidate biomarkers of in medical treatment, block the ability the production of toxic oxygen therapeutic responsiveness into of growth hormone to burn fat and scavenging molecules, or 'free radicals', national and international clinical trials build muscle. in the intracellular energy warehouse of personalised medicine strategies of cells, the mitochondria. These free for pancreatic cancer. The Garvan _ Demonstrated that burning fats, as radicals trigger insulin resistance. led consortium called PRIMe opposed to carbohydrates, is not (Pharmacogenomic Research for enough to promote fat loss because _ Demonstrated that extensive gene Individualised Medicine) is a new the body compensates by converting silencing is common in cancer, multi-institutional initiative funded by the unburned carbohydrate into fat. encompassing many tumour suppressor a program grant from the Cancer and neighbouring genes, non-coding Council NSW. RNA, intergenic regions and microRNAs. Up to 3% of the genome may be affected by epigenetic remodelling in cancer cells. Cancer Program CANCER PROGRAM ...... LEADER Professor Rob Sutherland FAA 19

Program Overview

Although derived from normal cells, cancer cells have distinctive features that can be exploited to aid diagnosis, prognosis, treatment and prevention. To do this, we need to know much more about the fundamental processes that govern cell behaviour: their division, their survival, their motility and their differentiation into complex tissue structures. With this knowledge we will be better able to stop the formation, spread and early growth of cancers.

As well as basic research into genetics/epigenetics and the cellular and molecular biology of cancer, the Cancer Program has six translational research groups that study a number of the most commonly diagnosed and most lethal cancers: breast, colorectal (bowel), lung, ovarian, pancreatic and prostate.

Program Highlights suppressor protein in cancer cells. It limitation to the successful treatment could be argued that p53 is the most of breast cancer. _ Demonstrated how the protein Bag-1 important tumour suppressor, inhibits apoptosis (cell death) in sometimes referred to as “the _ In collaboration with Professor Wayne normal breast epithelial cells and how guardian of the genome”. Tilley, University of Adelaide, we it may play a role in the early identified the mechanism of androgen development of breast cancer. _ Identified novel microRNAs that are receptor inhibition of oestrogen action commonly epigenetically deregulated in breast cancer. _ Used new protein technology to in bladder and prostate cancers — identify that a specific group of cell providing exciting new diagnostic _ Demonstrated a partial loss of the signalling proteins, Src family kinases, targets for detection. SATB1 protein in lung cancer, and represent potential therapeutic targets showed that this loss indicates a poor in basal breast cancer, an aggressive _ Identified that the oncogenic signalling prognosis. sub-type of breast cancer. protein Gab2 plays an important role in early breast cancer development. _ In collaboration with Dr Erik Knudsen, _ Showed that cell cycle genes, cyclin Kimmel Cancer Center, Philadelphia, E1 and cyclin E2, which are usually _ Identified CCBE1 as a potential we identified that the cell cycle co-regulated and so are believed to be tumour suppressor gene in ovarian protein cyclin D1b is a marker of poor functionally very similar, are regulated cancer that is inactivated by prognosis in breast cancer. differently in breast cancer cells. epigenetic changes in DNA. _ Identified new serum biomarkers for _ Identified that the MCC protein, _ Demonstrated the importance of therapeutic response to the which we had already shown to be transcription factor GATA-2 in the chemotherapy drug docetaxel in “switched off” in colon cancer, is transition to aggressive prostate advanced prostate cancer. important for the protection of DNA cancer, which is resistant to hormone from environmental damage. treatment. _ Characterised a new 5 biomarker panel that predicts outcome in early _ Demonstrated that extensive gene _ Identified that the Runx2 gene, well breast cancer. silencing is common in cancer, known as a master controller of bone encompassing many tumour suppressor development, also controls normal _ Identified roles for aberrant expression — as well as neighbouring — genes, breast development, and is a potential of Bag-1, CAIX, beta-catenin, non-coding RNA, intergenic regions mediator of breast cancer progression. StarD10, Notch-1, Her-2, Gab2 and and microRNAs. Up to 3% of the several components of the PI3 kinase genome may be affected by epigenetic _ Undertook a major review of breast pathway in defining cancer types and remodelling in cancer cells, resulting in cancer resistance to commonly used outcomes in breast cancer patients. a brake in activity in those cells. endocrine therapies (such as tamoxifen) which highlighted the _ In collaboration with Dr Karen _ Discovered a novel microRNA potential for emerging technologies to Knudsen, Kimmel Cancer Center, Professor Roger Daly pathway regulating the p53 tumour help us better understand this major Philadelphia, we documented how the CANCER PROGRAM CANCER PROGRAM ...... 20 21

various proteins (splice variants) that People Highlights _ Three Cancer Institute NSW Susan Clark is President of the _ Senior staff members in the Cancer _ Heidi Hilton, Nicholas Sigglekow, can be encoded by the cyclin D1 gene infrastructure grants totalling $1m Australian Epigenome Alliance, the Program are members of 16 Editorial Rebecca Hinshelwood and Kate function in prostate cancer. _ Dr Alison Butt was appointed were awarded to the Cancer Research Australian Member and Boards, including Breast Cancer On- Patterson were awarded PhDs President of the Australian Society Program, two to continue support of Representative of the Asian Line, Breast Cancer Research, British (UNSW). _ Developed new technology and for Medical Research (ASMR). the ACRF Genomics Facility and one Epigenome Alliance, and a Steering Journal of Cancer, Endocrine-Related methodology for analysis of the to develop primary pancreatic cancer Group Committee Member of the Cancer, Endocrinology, Epigenomics, _ Paul Chen was awarded a Master of human 'epigenome' — in other words, _ Professors Andrew Biankin, Rob xenografts with detailed genetic and International Human Epigenome Molecular Biotechnology and World Surgery (University of Sydney). for all the reversible chemical Sutherland and Susan Clark, in molecular information. Consortium; Dr Alison Butt is a member Journal of Gastroenterology. modifications to DNA and its conjunction with Associate Professor of ASMR and Women in Science _ Sarah Sutherland was awarded the Jan associated proteins that determine Sean Grimmond from the Institute for _ The Cancer Program's application to Enquiry Network, Inc; Professor Marie _ Professor Susan Clark was appointed Coppleson Memorial Prize for Cancer when genes can be expressed. Molecular Bioscience, University of Perpetual Trustees, led by Professors Dziadek is a member of the Australian to the Scientific Advisory Board of Medicine at the University of Sydney Queensland, were awarded an NHMRC Roger Daly and Liz Musgrove, was Research Council (ARC)/NHMRC the Institute of Predictive and for her MB BS Honours Project. _ Developed a novel algorithm and web- Medical Bioinformatics, Genomics and successful in funding the purchase of Research Network in Genes and Personalised Medicine of Cancer based software program that helps Proteomics Program Grant worth four essential pieces of equipment for Environment in Development; and (IMPPC), Barcelona, Spain as well as _ Saul Bert, Sam Al-Sohaily, Warwick identify genetic subtypes of cancer. $27.5m to establish the Australian the Institute. Professor Rob Sutherland is a member the Editorial Board of Epigenomics. Locke, Brian Gloss and Brian Lee were Pancreatic Cancer Genome Initiative. of the International Breast Cancer She was also appointed Chair of the awarded Cancer Institute NSW _ Identified pathways (myc/E2F) that This effort aims to characterise fully _ Dr Alex Swarbrick, in conjunction with Study Group, TransHERA and the Garvan Appointments and Promotions Research Scholarships. provide new therapeutic targets for some 400 pancreatic cancers at a Dr Robert Brink from the Immunology National Breast Cancer Foundation Committee and Deputy Chair of the non-oestrogen responsive breast genomic, epigenomic and transcriptomic Program, was awarded an NHMRC Novel Concept/Pilot Study Award Garvan Higher Degrees Committee. _ Emily Stoddart was awarded a UNSW cancers, for which no targeted level as part of the International Project Grant to study the genes Sub-Committee. Research Excellence Award. therapies currently exist. Cancer Genome Consortium controlling multiple myeloma. _ Associate Professor Chris Ormandy (www.icgc.org). The project brings _ Several members of the Cancer was appointed to the Scientific _ Saul Bert was awarded a Faculty of _ Identified that the degree of clearance together major international centres _ Dr Matthew Naylor was awarded a Program served on grant review Advisory Boards of the National Breast Medicine Rising Star Award. around a tumour when removed for pancreatic research including Johns UNSW Goldstar Award. panels: Professor Rob Sutherland as a Cancer Foundation and the Australian surgically is important for the long Hopkins University and the University member of the Advisory Group for the Phenomics Network and as Chair of _ Warwick Locke was awarded the term survival of patients treated for of Verona. _ Andrew Biankin and James Kench were Foundation for Science and Research Garvan's Higher Degrees Committee. National Breast Cancer Postgraduate pancreatic cancer, and that this finding promoted to Conjoint Professor at the Technology, Wellington, New Zealand; Scholarship, 2009. should inform future clinical trials _ Dr Lisa Horvath, Professor Rob University of NSW (UNSW) and Professor Susan Clark on the NHMRC _ Professor Rob Sutherland, Professor involving radiotherapy. Sutherland and Professor Roger Daly, University of Sydney respectively. Disciplinary Panel 1e Genetics and the Liz Musgrove and Associate Professor _ Carole Tactacan, Yuwei Phua, Saul in conjunction with Dr Michael Boyer NIH review panel for the Epigenetics Sue Henshall are members of the Bert, Anne-Marie Mooney and Jeremy _ Advanced candidate biomarkers of at the Sydney Cancer Centre, were _ Professor Rob Sutherland was made a Roadmap Technology Development Organising Committee and the Humphris were awarded Australian therapeutic responsiveness into awarded a Cancer Australia grant to Life Member of the Australian Cancer Group in Washington, USA; Associate International Advisory Group for the Postgraduate Awards from UNSW to national and international clinical trials identify and target Docetaxel Research Foundation, and was appointed Professor Chris Ormandy for the 5th PacRim Breast and Prostate commence their PhDs in 2010. of personalised medicine strategies resistance in hormone refractory as a Board Member of the Adelaide Victorian Breast Cancer Research Cancer Meeting to be held in for pancreatic cancer. The Garvan prostate cancer. Cancer Research Institute and as Consortium (VBCRC) Program Review Kingscliff, NSW in 2011. _ Cancer Program PhD students led consortium called PRIMe Garvan's representative of The Cancer Board; Professor Marie Dziadek for received prizes for their conference (Pharmacogenomic Research for _ Professor Susan Clark received Council NSW Member's Assembly. the ARC Future Fellowships Selection _ Associate Professor Sue Henshall poster presentations: Saul Bert Individualised Medicine) is a new Australia's “Top Ten” National Health Advisory Committee; and Dr Alison wrote an invited editorial for Annals received the Cancer Institute NSW multi-institutional initiative funded by and Medical Research (NHMRC) _ Professor Andrew Biankin was Butt for the NHMRC. of Internal Medicine on prognostic Award for Excellence in oral a program grant from the Cancer Scientist Award for 2009 and was appointed co-lead of the Australian markers in prostate cancer. presentation at the St Vincent's Council NSW. promoted to Senior Principal Research Pancreatic Cancer Project, Clinical _ Professor Liz Musgrove joined the Symposium and Rebecca Hinshelwood Fellow at Garvan. Lead of the Australian Pancreatic Editorial Board of a new journal, Genes _ Professor Liz Musgrove wrote an was awarded a poster prize at the _ Showed that standardised reporting in Cancer Genome Initiative, member of and Cancer, and commenced a invited editorial for Breast Cancer Epigenetics meeting in Melbourne, pancreatic cancer histopathology _ Dr Darren Saunders received a Life the ICGC Tissue and Clinical second term on the Scientific Advisory Research on a new class of drugs. December 2009. increased the accuracy of diagnosis. Sciences Research Award from the Annotation Working Group and Board of CellBank Australia. We then facilitated the Australia-wide NSW Office for Science & Medical member of the writing team for the _ Associate Professor Maija Kohonen- _ Dr Marcel Coolen was awarded a five implementation of the approach. Research and a Career Development ICGC Marker Paper to be published in _ Professor Roger Daly was appointed Corish was promoted to Garvan's Faculty. year tenure-track Research Fellowship from the Cancer Institute early 2010. to the Editorial Board of Critical Fellowship at The Radboud University _ In collaboration with the Cancer NSW to return to Garvan from Reviews in Oncogenesis and continued _ Emily Colvin was awarded the Cancer Nijmegen Medical Centre, Netherlands Council NSW developed a postdoctoral work in Canada. _ Cancer Program senior scientists are to serve on the Cancer Institute NSW Institute NSW 2009 Premier's Award to start 2010. multimedia/DVD support package for members of several major national Research Advisory Committee. for Outstanding Research Scholar. patients with pancreatic cancer and and international networks: Professor their families. CANCER PROGRAM CANCER PROGRAM ...... 22 23

Basic Cancer Research addition, we have identified a novel effect of another signalling protein, cortactin, on the cell cycle machinery of head and neck cancer cells that leads to their increased Cell Cycle Group proliferation. Finally, we have established new methodologies to characterise global Group Leader Professor Liz Musgrove alterations in protein phosphorylation associated with cellular signalling events. These are being used to identify novel therapeutic targets and prognostic markers in Female steroid hormones like oestrogen and progesterone strongly influence cell cancers refractory to current treatment regimens. For example, we have identified reproduction in the breast. We are particularly interested in how these hormones that basal breast cancers are characterised by a Src kinase signalling network, and act on the cell cycle machinery and how control over the cell cycle is lost in breast related research projects on pancreatic cancer, docetaxel-resistant prostate cancer cancer cells. Our current work concentrates on the cell cycle genes c-Myc, cyclin and hormone-insensitive breast cancer are underway. D1 and cyclin E2, all of which are targeted by oestrogen and are overexpressed in breast cancer. In collaboration with the Steroid Hormone Action and Breast Cancer Epigenetics Group Translational Groups we are searching for new genes that might link oestrogen Group Leader Professor Susan Clark action with the cell cycle and so could be involved in resistance of certain breast cancers to the anti-oestrogen tamoxifen. We are collaborating with the Peter Cancer cells can modify the expression of critical cancer genes independently of the MacCallum Cancer Institute in Melbourne and the Diamantina Institute in Brisbane DNA sequence, using two epigenetic biochemical processes called DNA methylation to undertake functional screens to identify genes involved in endocrine resistance. Dr Laurent Pangon and histone modification. Our research focuses on understanding the mechanism Dessislava Mladenova that triggers abnormal methylation and histone modification between normal and Steroid Hormone Action Group cancer cells. We have developed different methods to detect methylation changes Group Leader Professor Rob Sutherland FAA during early cancer development and have discovered that these epigenetic changes can take place not only in single genes, but can also occur across very large Our research aims to determine and characterise the genes that mediate the actions regions of DNA during the spread of cancer. These changes provide novel tumour of the sex steroid hormones oestrogen, progesterone, and androgens in steroid- "signatures" for cancer diagnosis as well as potential targets for cancer therapy. We responsive cancers (breast, prostate and ovarian). These constitute a third of all are now trying to determine which changes are specific to breast and prostate newly diagnosed cancers. cancer and the sequence of events that trigger these changes so that we can try to reverse the process. This is a large and complex project and our work forms part of In collaboration with the Cell Cycle and Apoptosis Groups we have identified and are the international effort on unravelling the human epigenome. characterising a number of steroid-regulated genes involved in the control of cell proliferation, cell differentiation and cell death in breast cancer. In partnership with Development Group the Breast and Prostate Cancer Groups and the Cancer Development Laboratory we Group Leader Associate Professor Chris Ormandy have demonstrated that some of these genes are new markers of cancer progression and response to therapy and novel targets for the development of new Development of the mammary gland occurs in defined stages that are governed by cancer therapies. the hormones that regulate reproductive events. We hypothesise that genes controlling normal mammary development can become mutated or deregulated in Apoptosis Research Group breast cancer and thus contribute to the disease process. We have discovered that Group Leader Dr Alison Butt the transcription factor Elf5 controls the development of the mammary gland during pregnancy and also regulates the proliferation and function of breast cancer Oestrogen not only causes breast cancer cells to proliferate but it also protects cells. We are investigating how Elf5 exerts these effects to provide a way to them from apoptosis (cell death). We are investigating how this occurs and are therapeutically target this mechanism. identifying the genes that regulate this process. Such studies will enable us to understand how these genes may influence the way anti-oestrogens such as Tumour Progression Group tamoxifen can effectively kill breast cancer cells. In other projects we are examining Group Leader Dr Alex Swarbrick how novel compounds derived from plants induce apoptosis in breast cancer cells. This could lead to their development as new therapies for the treatment of breast Most aggressive cancers have two features in common: they proliferate endlessly cancer as well as other cancers. (have high self renewal) and contain mostly unspecialised, poorly differentiated cells. We are investigating genes that control self renewal and differentiation in cancer, Signal Transduction Group with a particular focus on breast cancer. Together with the Breast Cancer Group and Group Leader Professor Roger Daly external collaborators we have discovered that several genes are key controllers of the growth and metastasis (spread) of poorly differentiated cancers. These include Our research focuses on how signals regulating biological processes such as cell the transcriptional regulator Id1, the Hedgehog signalling protein, and also the non- proliferation, survival and motility are transmitted within the cell, and how these coding microRNA-380. Understanding the contribution of these genes to cancer signals are altered in cancer cells. We have determined that a key signalling protein, progression will help us predict the behaviour of aggressive metastatic cancers and Gab2, is highly expressed at very early stages of breast cancer development, and may ultimately lead to the development of new drugs to stop their growth. characterised how this protein promotes cell motility as well as cell proliferation. In CANCER PROGRAM CANCER PROGRAM ...... 24 25

Integrin and Cell Biology Group Left: Dr Falko Hochgräfe and Emily Stoddart Group Leader Dr Matthew Naylor Right: Professor Andrew Biankin Our research aims to understand the mechanisms that regulate cell fate decisions during the progression of cancer to metastatic disease. Integrins mediate the adhesion of cells to the extracellular matrix and provide cells with a positional identity in addition to coordinating growth factor and hormone signalling to control cell function. Modulation of integrin expression and function can alter the cancer phenotype. We are currently investigating integrin function during mammary and prostate gland development and in experimental models of carcinogenesis and metastasis. We are also investigating the role of several cell fate transcriptional regulators during mammary gland development, cancer and metastasis.

Translational Cancer Research ovarian cancer. We also aim to understand how such genes influence ovarian cancer development, which may additionally identify new treatment targets for women Breast Cancer with advanced disease. Group Leader Professor Rob Sutherland FAA Prostate Cancer In association with clinicians at several teaching hospitals in Sydney (St Vincent's, Group Leader Professor Rob Sutherland FAA Royal Prince Alfred/Sydney Cancer Centre and St George) and major national and international trials groups (Australia New Zealand Breast Cancer Trials Group and Our group is concerned with the identification of markers for therapeutic International Breast Cancer Study Group) we have developed large tissue banks and responsiveness, prognosis and early prostate disease. We take a multidisciplinary patient databases that are being used to identify markers of disease subtype, approach that utilises expertise from a number of cancer researchers within and disease progression and response to particular therapies. A major joint project with outside the Garvan, as well as clinicians and pathologists, particularly colleagues at the Cell Cycle, Apoptosis and Steroid Hormone Action Groups is identifying the St Vincent's Prostate Cancer Centre and the Sydney Cancer Centre, Royal Prince molecular markers of tamoxifen resistance, since loss of response to tamoxifen is a Alfred Hospital. We aim to identify genes and pathways whose expression changes major reason for treatment failure. We are also conducting collaborative studies in- can predict the development of aggressive life-threatening prostate cancer or house and with other institutions to define the role of newly-discovered breast resistance to chemotherapy used for the treatment of advanced stage prostate cancer. cancer genes in the disease process. Pancreatic Cancer Lung and Colorectal Cancer Group Leader Professor Andrew Biankin Group Leader Dr Maija Kohonen-Corish Pancreatic cancer is the fourth leading cause of cancer death in Western societies, Our area of expertise is colorectal and lung cancer genetics and epigenetics. We with a five year survival rate of less than 5%. The treatment and survival of patients examine the gene profiles of resected tumour tissues and correlate them with with pancreatic cancer has not changed for over thirty years because there has patient clinical outcomes. The challenge is to work out which key gene alterations been little research into the molecular and cell biology associated with it. Our and biomarkers are the most useful for determining prognosis and treatment projects focus on improving outcomes for patients by defining molecular outcomes, in order to improve the clinical management of patients. We have phenotypes of pancreatic cancer using biomarkers to guide therapeutic decisions identified new genes that are inactivated through epigenetic mechanisms in cancer. and personalise therapies for pancreatic cancer. In addition, we are investigating In lung cancer we have analysed genes on chromosome 3p, an area of the genome molecular mechanisms of pancreatic carcinogenesis which may lead to the important in lung cancer development. We have shown that aberrant methylation development of novel therapeutic strategies. may be synchronised in this region and that the presence of this defect in the cancer is associated with poor patient prognosis. Cancer Development Laboratory Research Director Professor Marie Dziadek Ovarian Cancer Group Leader Dr Philippa O'Brien The Cancer Development Laboratory is investigating the potential for developing new cancer drugs against molecular targets expressed by cancer cells. Our current Our group works in collaboration with the Gynaecological Cancer Centre at the project aims to block the activity of a key enzyme that is highly expressed in many Royal Hospital for Women. Our major research goal is to use our combined expertise different types of cancer. This enzyme allows cancer cells to produce the energy and knowledge to identify new ways to diagnose women with early stage curable that is essential for their growth. We undertook a high throughput screen of a ovarian cancer. To this end we utilise a number of different approaches to identify chemical library in collaboration with the Walter and Eliza Hall Institute (at the the genes involved in the development of ovarian cancer, particularly its early WEHI-Bio21 HTS facility) in Melbourne and identified potent inhibitor compounds stages. Our primary focus is the identification of genes with altered methylation that showed efficacy in blocking cancer cell growth. These compounds will be patterns that have potential as blood-based diagnostic markers for early stage further developed in collaboration with commercial partners. The Kinghorn Cancer Centre THE KINGHORN CANCER CENTRE ...... 27

By the end of 2009, we had raised the necessary capital to build our Left: Garvan's Chief Operating Officer John Dakin (centre) with Bligh Voller Nield (BVN) architects James proposed translational cancer research centre — an exciting joint Grose and Mark Greene

initiative with St Vincent's Hospital. Known as the ‘Garvan St Vincent's Centre: BVN architects with Garvan's Associate Professor Cancer Centre' during the planning phase, the Centre will be named in Sue Henshall and Cate Smith honour of the Kinghorn Foundation, which made a very generous and Right: Artist’s impression of new Centre significant donation.

The Kinghorn Cancer Centre will provide over 10,000 m2 of research and clinical space. Adjoining Garvan, and a short walk from St Vincent's Hospital, the Centre will bring together around 250 cancer researchers, clinicians and support staff within a single location.

Vision patients' wellbeing. A central atrium will provide a focal point and collaborative The vision is to realise the promise of hub for patients, visitors, clinicians and personalised medicine for cancer researchers. State-of-the-art research patients by creating a world-renowned areas and core scientific facilities will be facility where research findings move situated on the upper and lower levels quickly into clinical care and clinical of the Centre, visible from the atrium challenges drive laboratory research. and a physical representation of the Centre's aim to build bridges between The Centre will complement other cancer research and patient care. cancer initiatives being planned around Australia, all of which have different Contributing to the Vision emphases and strengths. The cost of building and equipping The Design and Inclusions Kinghorn Cancer Centre will be around $110m. The Centre is now fully funded, Architectural practice Bligh Voller Nield thanks to a $70m grant from the (BVN) has designed an environment of Commonwealth Government's Health warmth and life, by using timber and and Hospitals Fund; the generous other natural finishes and by maximising support of many private donors; and natural light and a sense of space. the Trustees of St Vincent's, who have provided a site. Clinical areas including outpatient chemotherapy, consulting rooms and a Building works started in March 2010. Wellness Centre will have a view over Completion is expected in the latter half gardens, a feature proven to benefit of 2011. Diabetes & Obesity Program DIABETES & OBESITY PROGRAM ...... LEADER Professor David James FAA 29

Program Overview

The growing incidence of obesity is driving a worldwide epidemic in Type 2 diabetes, a disease that already affects 1 in 10 Australians. Research in this program is focused on the molecular regulation of body weight and fuel metabolism, and on obtaining a better understanding of Type 2 diabetes at multiple levels. There is a particular emphasis on the release of insulin and its mode of action in normal and disease states. Research strengths include live cell microscopy, the use of mass spectrometry for the discovery of new molecules affected by metabolic disease, in vivo gene manipulation and metabolic studies in humans.

Program Highlights _ Demonstrated that burning fats, as _ Jamie Lopez was awarded his PhD opposed to carbohydrates, is not and a postdoctoral fellowship from _ Showed that overeating generates the enough to promote fat loss because NHMRC to undertake postdoctoral production of toxic oxygen scavenging the body compensates by converting study at the Peter Mac in Melbourne. molecules, or 'free radicals', in the the unburned carbohydrate into fat. intracellular energy warehouse of cells, _ Yvonne Ng was awarded her PhD the mitochondria. These free radicals _ Indicated that diets high in medium chain from UNSW. trigger insulin resistance and fats (such as coconut oil) have a less overriding their production is of detrimental effect on insulin action in _ Professor Ted Kraegen spent several benefit in animal models. muscle than long chain fats (animal fats). months on sabbatical leave with Professor Keith Frayn, University of _ Found that fats disrupt movement People Highlights Oxford UK. During this time, Professor of protein out of the cellular protein- Kraegen gave a number of invited folding compartment in pancreatic _ Associate Professor Trevor Biden and seminars to UK research groups. insulin-producing cells, triggering Dr Georg Ramm were awarded cell death. NHMRC project grants. _ Dr Jiming Ye was appointed Associate Professor at RMIT University in _ Showed that different forms of the _ Dr Ross Laybutt was awarded a Melbourne, where he will continue his PKC enzyme family cause insulin project grant from the Juvenile work on traditional Chinese medicine. resistance in different ways, raising Diabetes Research Foundation. the potential for combination therapy. _ Dr Kyle Hoehn, a postdoctoral fellow _ Dr Carsten Schmitz-Peiffer and in the James lab was appointed to a _ Identified a novel role for the scaffold Associate Professor Trevor Biden prestigious position at the University protein, actin, in controlling the insertion signed a collaborative agreement with of Virginia in Charlottesville, where he of glucose transport molecules into the Californian company Kai will commence his career as an the cell surface of fat cells, one of the Pharmaceuticals to test PKC epsilon independent research scientist. most important actions of insulin. inhibitors in models of Type 2 diabetes. _ Yvonne Ng and Alex Rowland _ Showed that increasing the delivery of _ Dr Alex Viardot successfully obtained delivered oral presentations at the fat into muscle mitochondria reduces his PhD degree and was awarded an American Diabetes Association insulin resistance. NHMRC travelling fellowship. meeting in New Orleans.

Dr Nigel Turner DIABETES & OBESITY PROGRAM DIABETES & OBESITY PROGRAM ...... 30 31

Research Groups Anthea Bakopanos

Appetite and Adiposity in Pre-diabetes and Prader Willi Syndrome (PWS) Group Leader Professor Lesley Campbell AM

Our group focuses on the underlying defects in metabolism and appetite control in pre-diabetes and in the commonest genetic obesity disorder, Prader Willi Syndrome (PWS). The latter is associated with relentless weight gain after childhood and can be very difficult to manage. We undertook clinical studies in collaboration with Royal Prince Alfred Hospital PWS Clinic and in collaboration with Professor Herzog of Neuroscience we examine the role, and possible control, of satiety hormones and involvement of inflammation in PWS.

In the pre-diabetes area, we examine heritable factors in individuals predisposed to Type 2 diabetes. For example, overfeeding studies undertaken in 2009 showed that people with relatives with Type 2 diabetes, who are otherwise healthy, gained more weight and showed more metabolic decline than similarly healthy people whose relatives did not have Type 2 diabetes.

Fat and Insulin Resistance Group Leader Professor Don Chisholm AO disease. Either the cell 'burns out', generates an excess of harmful products, or We study patients with Hepatitis C, which is associated with insulin resistance and accumulates unmanageable amounts of unusable proteins, which ultimately lead to predisposition to Type 2 diabetes. We have shown the insulin resistance is, cell death. If the mechanism by which these stressors induce cell death can be surprisingly, in muscle rather than liver and is reversed with successful treatment of elucidated, this may enable identification of potential points of intervention to help the virus. We are now examining the molecular mechanism involved. We also cells deal with extra demands. continue our work on abdominal obesity, examining the role of a transcription factor, Islet 1, unique to visceral fat. We use adipose tissue transplantation in mice to Human Physiology examine interactions between adipose tissue and nervous and endothelial cells in Group Leader Dr Jerry Greenfield the generation of insulin resistance. In collaboration with the Cellular Systems Biology group, we are undertaking a major Molecular Metabolism study to identify defects in insulin signal transduction in skeletal muscle from at-risk Group Leader Associate Professor Greg Cooney individuals. We are also examining the characteristics of a group of obese people who seem to be protected from developing insulin resistance and diabetes. In Fat accumulation causes problems with metabolism that can lead to Type 2 addition, studies have been established examining the effects of glutamine, an diabetes, heart disease and stroke. The major focus of the Cooney group is to amino acid, on metabolism, both in isolation and in combination with a new diabetes understand factors (genetic and environmental) that control fat accumulation in medication. Glutamine appears to have a promising effect on glucose lowering after muscle and liver and to use this information to devise strategies to reduce fat in a meal and may offer a simple, novel and effective treatment in Type 2 diabetes. In these tissues and improve insulin action. When fat enters a cell from blood there are another study, we are examining the possible role of the autonomic nervous system two major choices for its fate. It is either stored as an intracellular lipid or it is in the development of diabetes and obesity. channelled into the mitochondria, where it is burned to produce energy. We are studying the regulation of glucose and fatty acid metabolism and energy production Phospholipid Biology by mitochondria and how tissue metabolism changes at different times of the day. Group Leader Dr Will Hughes This could help explain the contribution of increased food availability and altered eating habits to the rapid increase in obesity and metabolic disease. Phospholipids are the basic building blocks of cell membranes but, as is becoming clearer, some are also dynamically regulated to enable control of many of the major ER Stress and Protein Misfolding functions of cells. Two such examples are the stimulated secretion of insulin from Group Leader Associate Professor Antony Cooper pancreatic beta cells after a meal, and the movement of glucose transporter GLUT4 to the plasma membrane in muscle cells to allow glucose uptake in response to Our group aims to understand how cells cope, or fail to cope, with the stress that insulin. We continue to use state-of-the-art live cell microscopy to see where and can result from the over-production of proteins and misfolding of proteins within a when in individual cells the dynamic changes in phospholipids occur to determine cellular compartment called the endoplasmic reticulum (ER). ER stress is directly how they may regulate insulin release or GLUT4 movement. In collaboration with applicable to a growing number of diseases including diabetes, as well as many the Cellular Systems Biology and Molecular Metabolism groups, we aim to identify diseases of the brain like Huntington's, Parkinson's, Alzheimer's and motor neuron precisely which intracellular processes may be defective in diabetes. DIABETES & OBESITY PROGRAM DIABETES & OBESITY PROGRAM ...... 32 33

Cellular Systems Biology Dr James Cantley and Dr Dorit Samocha Bonet Group Leader Professor David James FAA

A major action of insulin that becomes defective in Type 2 diabetes is the regulated entry of nutrients into muscle and fat cells. The goal of our group is to use newly developed molecular imaging methods to study the insulin-regulated movement of the GLUT4 glucose transporter as well as other processes in insulin responsive cell types. Also using mass spectrometry, novel molecules involved in insulin action have been identified and these represent the focus of many future studies. These studies dovetail with a major investigation into the mechanism of insulin resistance in muscle and fat, with recent studies from the group highlighting an important role for oxidative stress.

Diabetes and Metabolism Group Leader Professor Edward Kraegen

Understanding how too much fat causes insulin resistance in muscle and liver is the major thrust of our work. Various experimental models and state-of-the-art Jane Reznick techniques are being used to identify and manipulate key proteins in muscle that link fat metabolism to insulin action. Work in 2009 with collaborators in Hong Kong and possible future therapy for Type 2 diabetes. Another major project is examining the the UK has established important signalling pathways, involving the protein APPL1, molecular links between fatty acids and beta cell death, with particular emphasis on whereby the hormone adiponectin and enzyme AMP-kinase, a major intracellular ER stress. We have now shown that fatty acids disrupt the movement of secretory regulator of cellular energy status, could influence potency of insulin action in proteins within beta cells and that this is a major trigger of ER stress. Our ongoing muscle. Further work with Boston University, partly funded by the US funding work is focused on delineating how and where this disruption occurs. agency NIH, has opened up new ways of looking at the early stages of muscle insulin resistance in response to increased glucose availability. They stress the Islet Biology importance of metabolic factors ahead of insulin signalling impairment. Studies using Group Leader Dr Ross Laybutt traditional Chinese medicines, with collaborators in Shanghai, may help us identify new insulin-sensitising agents that could be more useful than current therapeutics. Pancreatic beta-cell failure is fundamental to the development of diabetes. Our goal Excitingly, some of these molecules modulate AMP-kinase. is to identify mechanisms responsible for the beta-cell destruction and the loss of insulin secretion that cause diabetes. The major hypothesis under investigation is Obesity in Diabetes that in Type 2 diabetes a gradual rise in blood glucose (hyperglycaemia) and lipid Group Leader Associate Professor Katherine Samaras levels leads to a loss of the unique expression pattern of genes necessary for appropriate insulin secretion. This worsens hyperglycaemia, which causes further Obesity is a major accelerating factor in the development of Type 2 diabetes in beta-cell dedifferentiation and eventually beta-cell death. Studies have also made humans. We have been studying the progress of obese diabetic patients in response important contributions to understanding how cytokines, lipids and high glucose to weight loss regimens, finding glucose tolerance can be restored to normal after induce stress within the endoplasmic reticulum (ER) and are investigating ER stress bariatric surgery. Our results show these improvements are not explained by weight as a potential mechanism for beta cell dysfunction and destruction in Type 1 and loss. We have also shown that humans with obesity and diabetes have greater levels Type 2 diabetes. of genes regulating inflammation in abdominal fat. We are currently investigating the role of circulatory and tissue-based inflammation in the reversal of diabetes with Insulin Signalling weight reduction, which will provide insights into how diabetes develops and Group Leader Dr Carsten Schmitz-Peiffer identify potential targets for treating the commonest form of diabetes. We focus on the lipid metabolites that disrupt insulin signalling and how these Diabetes Signalling Unit contribute to insulin resistance. This year we demonstrated the effectiveness of blocking the accumulation of such intermediates with a novel compound, which Beta Cell Signalling represents a new approach to treating insulin resistance. Another interest of our Group Leader Associate Professor Trevor Biden group is the protein kinase C (PKC) family of enzymes, and we have shown that while two distinct PKC members (PKCd and PKCe) each play a role in generating Increased beta cell death and disruption of beta cell function are characteristics of insulin resistance due to fat oversupply, they do so in different ways, either by both Type 1 and Type 2 diabetes. We have discovered that inhibiting the enzyme promoting lipid synthesis or by affecting its partitioning in insulin-sensitive tissues. protein kinase C epsilon (PKCe), dramatically improves insulin secretion in models Proteomic approaches indicate that PKCs control the levels of several enzymes Type 2 diabetes and have shown that the mechanism involves alteration in beta cell involved in lipid metabolism. In addition, PKCe regulates the insulin receptor itself, lipid metabolism. Studies are underway to identify inhibitors of this enzyme as a promoting its cellular internalisation to reduce its downstream signalling. Diabetes Vaccine Development Centre DIABETES VACCINE DEVELOPMENT CENTRE ...... CEO Ms Rowena Tucker 35

Overview Highlights Membership of the DVDC Scientific Advisory Committee The Diabetes Vaccine Development Centre (DVDC) was established in 2003 _ Received confirmation of a further through a major joint initiative of the National Health and Medical Research Council $5m over three years from JDRF to Professor Ian Frazer FAA (Chair) (NHMRC) and the New York based Juvenile Diabetes Research Foundation (JDRF). support DVDC activities. Director, Diamantina Institute for Cancer Immunology & Metabolic Medicine With the assistance of a grant from the NSW Government, DVDC relocated from _ Invested in the development of a new Melbourne to Garvan in 2007. It became a company limited by guarantee with database for the management of its Dr Robert A. Goldstein, MD, PhD Garvan as the sole member in 2008. INIT II clinical trial which will serve as a Senior Vice President, Scientific Affairs, platform for the management of other Juvenile Diabetes Research Foundation DVDC is governed by a Board representing its major stakeholders (Garvan, JDRF clinical trials in the future. International (JDRF) and NHMRC), as well as internationally recognised scientists and biotechnology executives with expertise in the fields of diabetes and vaccine development. _ Employed a Senior Clinical Research Professor Chris Goodnow FAA FRS Associate which now enables DVDC Director, Immunogenomics Laboratory Originally, the Centre's mission was to accelerate the development of one or more to undertake its own trial monitoring, & Director, Australian Phenomics Facility, vaccines that would prevent or delay the progress of Type 1 diabetes, however the and provide additional support and John Curtin School of Medical Research DVDC Board decided to broaden the focus to include clinical research on advice to the network of INIT II & The Australian National University Membership of the DVDC interventions and complications of Type 1 diabetes. investigators and study coordinators. Board Dr Carla Greenbaum DVDC has substantial in-house experience for the conduct of clinical trials, and co- _ Received a number of Expressions of Director, Diabetes Clinical Research Professor Don Chisholm AO (Chair) ordinates a network of 10 trial sites across Australia and New Zealand. Interest seeking DVDC involvement Benaroya Research Institute at Virginia Senior Principal Research Fellow, in multicentre Type 1 diabetes trials Mason, Seattle, USA Diabetes and Obesity Research DVDC received confirmation of a further $5m over three years from JDRF to — evidence that the DVDC profile Program, Garvan support DVDC activities. is growing. Professor Leonard C Harrison Head, Autoimmunity and Transplantation Professor John Shine AO FAA Scientific Program _ Successfully held the INIT II Annual Division, Walter and Eliza Hall Institute Executive Director, Garvan Meeting 26-27 November 2009 in of Medical Research Type 1 Diabetes Prevention Study, INIT II Melbourne. John Dakin This is a Phase 2, multi-centre, randomised, double blind, placebo-controlled trial of Professor Peter Colman (alternate to Chief Operating Officer, Garvan intranasal insulin (440IU) in children and young adults at risk of Type 1 diabetes. The _ Worked closely with JDRF Australia in Professor Harrison) aim of this project is to determine whether the administration of insulin via an the further development and Department of Diabetes and Paul Eisen intranasal route will result in a protective immune response. implementation of its research Endocrinology, Royal Melbourne VP Sales & Marketing, Australia & Asia strategy, including a substantial Hospital Pacific, KarmelSonix Pepidia-1, Phase 1b Study of Proinsulin (P1) Peptide Immunotherapy in proposal for an enhanced clinical trials New-onset Type 1 Diabetes infrastructure which would coordinate Stephen Higgs Professor Ian Frazer FAA Peptide immunotherapy represents a novel approach to preventing loss of insulin an inclusive network of clinical trial Chair of the Board of Directors Director, Diamantina Institute for production from the pancreas in Type 1 diabetes. The Pepidia-1 study, which is sites linking investigators, study JDRF Australia Cancer Immunology & Metabolic being conducted in the UK, aims to address the safety issue of whether, in patients nurses, and hospitals in each state Medicine with residual beta-cell function (new onset disease), P1 peptide administration around Australia. Dr Dorota Pawlak adversely affects the rate of beta-cell loss. Research Development Manager Stephen Higgs JDRF Australia Chair of the Board of Directors, JDRF Use of BAFF Blockers to Prevent Type 1 Diabetes in Man Australia DVDC is supporting pre-clinical studies aimed at testing a therapy targeting the Dr Roland Tisch B cell arm of the immune system. Using non-obese diabetic mice, this study aims Department of Microbiology & Christina Hardy to test the hypothesis that B-cell depletion, by way of BAFF-blockade, will restore Immunology, University of North Director, Business Development & Legal tolerance to islets and prevent diabetes occurrence. Carolina at Chapel Hill USA Affairs, Garvan

DVDC Ltd T 02 9295 8314 M 0403 254 255 E [email protected] Immunology Program IMMUNOLOGY PROGRAM ...... LEADER UNTIL 31.12.09 Professor Antony Basten AO FAA FTSE 37 LEADER FROM 1.1.10 Dr Robert Brink

Program Overview

Our immune system is designed to protect us from dangerous attacks whether they come from outside the body in the form of infections, or from inside the body in the form of cancer. At the same time, the system must learn to avoid attacking our own tissues or reacting to minor threats like pollens and house dust mites. When this balance is upset and the controls fail, the outcomes are diseases ranging from life threatening infections and spreading tumours to autoimmune conditions (eg rheumatoid arthritis and Type 1 diabetes) and allergies (eg asthma).

The work of the research team in the Garvan Immunology Program is divided between studying how a normal immune system functions in a balanced way and what goes wrong when disease occurs. To this end, use is made of the latest models of human diseases to improve our understanding of their pathology and devise better ways of treating them. Close ties therefore exist between the Program and Garvan's biotech company, G2 Therapies Ltd, which is currently commercialising a range of therapeutic antibodies made within the Immunology Program's laboratory.

Staff in immunology interact with colleagues from the Cancer, Neuroscience and Diabetes Programs. This reflects the importance of immune mechanisms in many different diseases and the value of immunological techniques when studying the differences between normality and disease in a wide range of target tissues.

Program Highlights _ Every month the prestigious Journal of _ Showed that the EBI2 gene, that Immunology features a previously produces a B cell surface protein of _ Discovered a promising therapeutic published paper, which is selected as a previously unknown function, is target for prevention of Type I 'pillar of immunology' article by the required to co-ordinate B cell migration diabetes, a molecule known as BCMA, editors for its “enormous impact on and differentiation during the early which effectively subdues the immune the field of immunology”. In November phases of antibody responses. cells that cause the disease. 2009, a paper co-authored by Dr Robert Brink and Professor Tony _ Showed that the three signalling _ Showed new ways of artificially Basten and published in Nature in molecules, TRAF2, TRAF3 and cIAP, boosting the numbers of a certain 1988 received this accolade. Cited function together to control B cell class of immune cells (regulatory T 944 times it describes the survival and are all potential B cell cells), a process which could be used development of the most widely used tumour suppressors, so they may to prevent the rejection of organ transgenic mouse model for studying prevent development of cancer in transplants or the development of the control of antibody responses. these cells. autoimmune diseases. _ Identified checkpoints during the _ Revealed that the body usually _ Defined a role for 'lipid rafts' — tiny development of B cells (immune cells manages to deploy a class of T cells fat-enriched platforms in cell which make antibodies), when any (known as T follicular helper cells) to membranes that appear to ramp up rogue cells present that can attack help B cells produce high quality the sensitivity of killer T cells — in 'self' are destroyed, so helping protect antibodies against “enemies” (foreign helping us mount an immune response us against autoimmune diseases. pathogens) and at the same time to viruses and cancers. prevent them from producing antibodies _ Produced and published the first against “self” (our own tissues). _ Elucidated and patented methods for detailed map of the rapid changes in improving the stability of antibody B cell migration and cell surface protein _ Showed that a gene known as STAT3 therapeutics, a novel class of drugs expression that occur during the early is critical in regulating the production with more than US $20 billion sales phase of an antibody response. of antibodies, which explains why each year. people with certain rare immunological Dr Robert Brink IMMUNOLOGY PROGRAM IMMUNOLOGY PROGRAM ...... 38 39

disorders, where that gene is mutated, People Highlights _ Tyani Chan received two travelling _ Dr Stuart Tangye was an invited cannot produce functional antibodies scholarships for the Keystone B cell plenary speaker at the Keystone to protect themselves against disease. _ Professor Jonathan Sprent was conference: the Keystone Symposia Symposium on “Immunologic Memory awarded an NHMRC Senior Principal Travel Scholarship 2009 and the and Host Defence”. _ Demonstrated that a tiny genetic Research Fellowship. UNSW Postgraduate Research Scheme irregularity in the gene encoding for Travel Scholarship 2009. _ Drs Jenny Gunton, Sue Mei Lau and the growth factor IL-21 greatly _ Dr Shane Grey was awarded both an Sue Lynn Lau received Diabetes boosts its expression, leading to the Australian Research Council 2009 _ Kendle Maslowski received this year's Australia Research Trust grants. development of Type 1 diabetes in Future Fellowship and an NHMRC Castle Harlan Award of $10,000 for mice. The absence of the irregularity, Senior Research Fellowship (he the best 2nd year PhD student at the _ Dr Jenny Gunton was awarded a two on the other hand, keeps IL-21 at accepted the latter). Garvan Institute. year JDRF grant for translational normal levels and prevents studies in islet transplantation in Type development of the disease. _ Kenneth Ho was awarded the Novartis _ Professors Jonathan Sprent and Tony 1 diabetes. Young Investigator award by the Basten were invited to speak in _ Identified high levels of a particular Endocrine Society of Australia for the symposia at the Korean Association of _ Dr Shane Grey gave a public seminar immune cell — a 'T helper cell' — in best presentation at the annual Immunologists meeting, Seoul, Korea. for Diabetes Australia (Pushing the the pancreatic insulin-producing cells scientific meeting in August 2009. Boundaries day) on the Australian of mice and humans prone to develop _ Professor Tony Basten was a clinical islet transplant trial. Type 1 diabetes. These cells appear to _ Dr Cecile King, Dr Shane Grey and Matthew Adams participant in the Cambridge Jessica Stolp originate in the gut and migrate to the Professor Tony Basten were invited to Immunology Forum, UK. _ Dr Jenny Gunton was elected pancreas, where they produce large speak at the Australasian Honorary Secretary of the Australian quantities of the IL-21 gene and so Autoimmunity Workshop. _ Dr Kylie Webster won a St Vincent's Diabetes Society, and Program contribute to disease onset. Research Symposium Award for Oral Organising Committee Chair for the _ Dr Daniel Christ was an invited speaker Presentation and a TSANZ (Transplant ADS annual scientific meeting. She _ Demonstrated that 'short chain fatty at Lorne BDI conference in Victoria Society of Australia and New Zealand) also became a Board Member of acids' (the by-products of bacterial and at Medimmune (Cambridge). He Young Investigator Award. Diabetes Australia and was an invited fermentation of insoluble dietary fibre was also session chair (Antibody speaker at the Endocrine Society of in the gut) bind to GPR43, a molecule engineering) at OzBio meeting. _ Tyani Chan won the NSW Flow Australia Seminar. expressed by immune cells that acts Cytometry Prize for her work on early as an anti-inflammatory receptor. _ Dr Daniel Christ and Professor B lymphocyte responses. _ Drs Cecile King, Robert Brink and Jonathan Sprent received a Cancer Stuart Tangye were awarded Project Institute New South Wales grant for _ Dr Sandra Gardam was awarded an Grants from the NHMRC. translational studies on Interleukin-2. NHMRC Overseas Biomedical Fellowship. _ Dr Cecile King was invited to give a _ Dr Tri Phan was an invited _ Dr Dominique Gatto was awarded a plenary talk at the annual Immunology international speaker at the16th one year pilot grant by the Alliance for of Diabetes Society meeting in Germinal Centre Conference, Lupus Research (US). Malmo, Sweden in May. Frankfurt, Germany. _ Vivian Turner was awarded an Australian _ Dr Robert Brink was an invited _ Kip Dudgeon received a Cancer Postgraduate Research Award. Keynote speaker at the Australasian Institute NSW - 2010 Research Society for Immunology NSW Branch Scholar Award. _ Peta Snikeris was awarded Honours Meeting, Bowral. Class 1 and a University Medal for best _ Helen McGuire and Kendle Maslowski Honours thesis of 2009 at the UNSW. _ Dr Robert Brink was an invited plenary were chosen to present in the speaker at 39th Annual Conference of prestigious Young Investigators Forum _ Drs Elissa Deenick and Mainthan the Australasian Society for Immunology. at the Annual ASI Scientific Meeting, Palendira were awarded travel Gold Coast. Gold Coast. scholarships to attend the Keystone Symposium on “Human Immunology _ Vivian Turner received a Cancer _ Helen McGuire received a travel grant and Immunodeficiencies” held in Institute NSW - 2010 Research from the UNSW Graduate Research Beijing in May 2009. Scholar Award. School (PRSS). IMMUNOLOGY PROGRAM IMMUNOLOGY PROGRAM ...... 40 41

_ Dr Sandra Gardam received the Garvan allowed her to present in a plenary Dr Jenny Gunton and Dr Sue Mei Lau Institute Thesis Prize for 2008. session at the Allergy and Asthma Keystone Symposium. _ Dr Cindy Ma was awarded a travel fellowship to attend the RIKEN _ Dr Martijn Bjiker received a Dutch Research Centre for Allergy & Cancer Society fellowship for two years. Immunology (RCAI) International Summer Program at Yokohama, Japan. _ Stacey Walters was awarded a Qantas scholarship for flights to attend the _ Drs Stuart Tangye and Robert Brink International Pancreas and Islet were invited plenary speakers at the Transplant Association's congress held "World Health Organization/ in Venice. International Union of Immunological Societies (IUIS) Expert Meeting on _ Dr Tri Phan was an invited speaker at Primary Immunodeficiencies the 17th Annual Conference of the (WHO/IUIS)", held in Dublin. Immunology Group of Victoria

_ Drs Stuart Tangye, Robert Brink and _ Dr Tatyana Chtanova was awarded Cecile King were invited speakers at a Ramaciotti establishment grant the "39th Annual scientific meeting of and a Fellowship from the Cancer the Australasian Society of Institute, NSW. Immunology", to be held on the Gold Research Groups Coast, QLD. _ Dr Di Yu was awarded a NHMRC Training Fellowship (Australia) and Cellular Immunity _ Dr Santi Suryani received a UNSW Cancer Institute NSW Early Career Group Leader Professor Jonathan Sprent FAA FRS Postgraduate Research Scheme Travel Fellowship. He was also an invited Scholarship to attend the " B Cells in speaker to The 1st International Our team is interested in the development and fate of T cells — white blood cells Context" Keystone Symposium held in Forum on Rheumatoid Arthritis, China; that participate in a variety of immune responses but can somehow distinguish New Mexico and was selected to give The 11th International Conference on between self and foreign antigens. One of the unknown questions that is central to an oral presentation at this meeting. Advances on Targeted Therapies, maintaining the immune system's homeostasis is how are these cells destroyed once France; The 2nd Australia-China their mission is complete and infections are overcome? We know that most self- _ Drs Stuart Tangye and Elissa Deenick Biomedical Research Conference, destruct while a few live on to become memory T cells, which are activated by a re- were invited to give oral presentations China; The 8th International infection, but we don't know the factors that determine their destiny. Application of at the “Human Immunology and symposium of Rheumatism Research our work lies in harnessing the immune system to boost its attack on cancerous Immunodeficiencies” Keystone Center, Korea; and the American tumours and, conversely, dampening down the immune response to treat Symposium held in Beijing in May. College of Rheumatology Annual autoimmune diseases. Scientific Meeting, San Francisco, USA. _ Dr Lucinda Berglund was awarded an B Cell Immunobiology NHMRC Postgraduate Research _ Alexis Vogelzang was awarded a Group Leader Dr Robert Brink and Emeritus Professor Antony Basten AO FAA FTSE Scholarship to undertake her doctoral UNSW Postgraduate Research Scheme studies. Travel Scholarship 2009 to attend the B lymphocytes (B cells) produce secreted antibodies in response to the entry of American Association of foreign substances and microorganisms into the body. Antibodies bind specifically to _ Lewis Cox was awarded his PhD. Immunologists meeting in Seattle. these foreign “antigens” and target them for destruction and elimination. Autoimmune diseases such as immune thrombocytopenic purpura, myasthenia _ Heidi Schilter won the TSANZ gravis and haemolytic anemia can arise when B cells produce rogue antibodies that (Thoracic Society of Australia and attack the body itself instead of the foreign invaders. The growth and survival of B New Zealand) Travel Award to present cells can also become dysregulated, leading to B cell malignancies such as lymphoma at the 2009 annual scientific meeting. and multiple myeloma. Our laboratory has developed a unique system that allows She also received a prize for best oral the detailed characterisation of B cells participating in all phases of an immune presentation in the field of response. This system is used to identify the genes, signalling pathways and Immunology and received the Stuart intercellular interactions that regulate B cell survival, proliferation, and differentiation Furler Travel Fund award which in the body. By understanding how B cells function we hope to reveal new strategies for improving vaccines, controlling autoimmune disease, and treating B cell cancers. IMMUNOLOGY PROGRAM IMMUNOLOGY PROGRAM ...... 42 43

Gene Therapy & Autoimmunity technology, completely bypassing the use of animals. These fragments can be Group Leader Dr Shane Grey produced in large quantities in bacteria and open up promising new routes for non- intravenous applications, imaging and therapy. We are applying our technology to Our laboratory is interested in the how and why of the immune system's attack on targets in cancer and inflammatory diseases. the body's tissues as it occurs during the rejection of organ grafts and in autoimmune disorders like Type I diabetes where the insulin-producing beta cells are B Cell Tolerance and Autoimmunity destroyed. Approaches include examining factors that regulate the immune attack Group Leader Dr Pablo Silveira on our own cells and investigating the molecular changes that occur in the tissue being attacked in the hope of, one day, being able to genetically engineer tissues Our ultimate goal is to prevent the immune system attacking the insulin producing that could withstand the assault. This strategy would alleviate the need for the toxic beta cells of the pancreas, which leads to Type 1 diabetes. Our research aims to immunosuppressive drugs currently required to promote successful organ identify the faulty mechanisms that allow the B cells recognising beta cell proteins transplantation and, in the case of Type I diabetes, enable creation of a 'death- to persist and thus activate the destructive T cells. We also aim to identify novel defying' beta cell as a novel cure. genes that control the generation and function of this aberrant population of B cells, findings that could form the basis for new therapies to prevent or reverse Type 1 Immunobiology diabetes in humans. Group Leader Dr Stuart Tangye Diabetes and Transcription Factors Our focus is on understanding the development of B cells — the population of white Group Leader Dr Jenny Gunton blood cells responsible for the production of protective antibodies — and the regulation of antibody responses. We are particularly interested in finding out how The causes of beta-cell failure are not well understood, but we know there are the immune system responds to infections or vaccinations by providing us with a changes in these cells' gene expression that can yield clues about what is going 'memory' of the response so that we cope faster and better following subsequent wrong. Through the use of a variety of tissue-specific knockout and transgenic mice exposure to the same infectious agent. The development of immunological memory we hope to identify why beta cell failure occurs as well as ways to improve beta cell involves interactions between B cells and 'helper' T cells — another subset of function and thereby treat human diabetes. We are currently focusing on a gene immune cells. Thus, a major focus of our work is to understand exactly how helper T called ARNT, which is decreased by 90% in the beta cell containing islets of people cells instruct B cells to produce antibodies. We are also studying several genetic with Type 2 diabetes. It seems to be a master gene that controls other genes conditions of the immune system, and corresponding mouse models, that result in involved in beta-cell function, including glucose breakdown and insulin production. immunodeficiencies — disorders whereby affected individuals are unable to mount We are now looking at ways to control ARNT. appropriate immune responses following exposure to some infections or pathogens. These diseases include X-linked lymphoproliferative disease, common variable Translational Immunology immunodeficiency and hyper-IgE syndrome. Overall, we hope to identify means to Group Leader Professor Charles Mackay FAA improve the immune response in individuals with immunodeficiencies and, conversely, ways in which the immune system of patients with autoimmune Professor Mackay took up a Chair at Monash University at the beginning of this diseases could be controlled. year. However, he continues to run an active group of students and postdocs at the Garvan. Their research has led to development of antibodies that can intervene in Mucosal Autoimmunity the inflammatory process, the final common pathway for many diseases, and are Group Leader Dr Cecile King being developed by G2 Therapies Ltd. They are also studying the link between diet, fatty acid binding proteins and asthma; and looking more broadly at the links Our laboratory is interested in the autoimmune responses that cause destruction of between inflammatory and metabolic diseases. The outcome is a new hypothesis tissues at the mucosal interface between the body's own tissues and the suggesting that gut microbes in conjunction with our diet, determine the nature of environment. Broad-based immunosuppression is commonly used to treat the more inflammatory responses. serious autoimmune diseases and transplant recipients, but it has an obvious drawback since we need a functioning immune system in order to thrive. The aim of A node of the Cooperative Research Centre for Asthma and Airways our research is to identify target molecules that will enable the selective suppression Head Professor Charles Mackay FAA Group leader Dr David Zahra of self-tissue-destructive cells. Our group focuses on the development of a promising therapeutic that neutralises Antibody Engineering the function of the cytokine GM-CSF. GM-CSF has been linked to a number of Group Leader Dr Daniel Christ inflammatory diseases including asthma and rheumatoid arthritis, and we have developed an antibody that blocks this cytokine. The antibody has been successfully Our laboratory is working on the development of novel antibody therapeutics. In 'humanised' and the epitope that our antibody binds on GM-CSF has been defined. particular, we are interested in the engineering of human antibody fragments, which The potential therapeutic is protected by two provisional patents and is now ready are considerably smaller than current monoclonal antibodies. Human antibody for pre-clinical and toxicology studies. A feasibility study is being conducted in fragments (such as domain antibodies) can be generated by genetic engineering collaboration with a major pharmaceutical company with the aim of fully licensing the therapeutic for pre-clinical and clinical development by the end of 2009. Neuroscience Program NEUROSCIENCE PROGRAM ...... LEADER Professor Herbert Herzog 45

Program Overview

The Neuroscience Research Program aims to increase our understanding of the neuronal systems involved in disorders such as Parkinson's disease, Alzheimer's disease, schizophrenia, eating disorders and hearing loss. We also investigate neuro-endocrine defects caused by the loss of growth hormone function. We aim to identify new therapeutic approaches in these areas, with a special interest in regeneration of the nervous system for therapeutic purposes. Much of our research strives to achieve a better understanding of the brain's control of body functions including the regulation of energy balance (intake and expenditure), which affects fertility, mood, and weight gain.

Program Highlights from nerve cells, knowledge that People Highlights should speed up the development of _ Found that sex hormones and the more effective drugs for treating _ Professor Herbert Herzog was an neurotransmitter neuropeptide Y Parkinson's Disease. invited plenary speaker at the 17th (NPY) work together to control fat International Symposium on Regulatory levels and bone density in the body. _ Demonstrated successful survival of Peptides in Santa Barbara, California, transplanted adult human olfactory USA where he also received the _ Showed that NPY receptors in the stem cells in a mouse model of age- 'Victor Mutt Award'. body, rather than the brain, regulate related hearing loss. fat burning and storage, and that _ Professor Herzog was also an invited blocking them can prevent fat gain. _ Showed the first evidence that plenary speaker at the 30th Winter growth hormone enhances sprint Neuropeptide Conference _ Identified the specific neuronal capacity, a selective aspect of Breckenridge, Colorado, USA; the 16th pathways in the brain that respond to physical performance. Obesity meeting in Kagoshima, Japan; pancreatic polypeptides and reduce the 1st International Neuropeptide appetite. This highlights a potential _ Demonstrated that Beta-blockers, a Festival in Salzburg, Austria; and the new way of treating obesity. commonly used blood pressure 1st Annual Meeting of the Austrian medication, cause obesity by slowing Association of Molecular Life Sciences _ Discovered the exact location of adult down metabolism and diminishing and Biotechnology, Innsbruck, Austria. taste bud stem cells, making it easier physical activity. to access and use them in _ Associate Professor Amanda Sainsbury- transplantation. _ Identified new growth hormone- Salis was invited to present the responsive genes that breakdown fat. Keynote Seminar at the 26th Annual _ Proved that inflammation in the brain Kinesiology Conference of the Australian prevents stem cell proliferation and _ Showed that SERMs, a class of Kinesiology Association in Sydney. neural repair, a finding that will have synthetic oestrogens commonly used important therapeutic implications for in medical treatment, block the ability _ Dr Sharon Oleskevich was an invited Parkinson's and Alzheimer's disease. of growth hormone to burn fat and speaker at the Hearing and Balance build muscle. Centre, St Vincent's Hospital. _ Revealed that NPY plays a central role in the correlation of bone mass with _ Demonstrated that measuring gene _ Dr Bryce Vissel was appointed to the bodyweight. expression changes in blood cells is Scientific Advisory Board for not as effective as a growth Parkinson's NSW; to the Editorial _ Made significant advances in our hormone doping test than measuring Board of Journal of Neurochemistry; understanding of dopamine release blood proteins. to the clinical trials group of the

Sabrina Riepler NEUROSCIENCE PROGRAM NEUROSCIENCE PROGRAM ...... 46 47

Hearing Research Group Leader Dr Sharon Oleskevich

Many forms of hearing loss result from the degeneration of hearing receptors (hair cells) in the inner ear. Hair cells degenerate with aging and exposure to excessive sound. We are exploring the transplantation of adult stem cells to help repair the hearing receptors. We have discovered that taste stem cells have a positive effect on hearing levels following transplantation into a mouse model of noise-induced deafness. In the past year we have extended this research to transplantation of human olfactory stem cells into a mouse model of age-related hearing loss. We are also exploring how deafness can change the way nerve cells in the brain communicate with each other. An international collaboration is underway to determine the anatomy and physiology of these changes.

Neurodegenerative Disorders — Repair and Regeneration Group Leader Dr Bryce Vissel

The Neurodegeneration Research Group identifies approaches for better understanding and treating Parkinson's disease, Alzheimer's disease and spinal Lesley Castillo Dr Bryce Vissel and Professor Herbert Herzog disorders. Our goal is to harness the nervous system's own repair systems and stem cells in order to stimulate the formation of new nerve cells and their connections. Australian and New Zealand Spinal Research Groups We also investigate how to block nerve cell loss. Our team has identified new Cord Injury Network; and as Network mechanisms for stimulating brain repair from stem cells in the brain and has also Facilitator for MS Research Australia. Adult Stem Cell Research discovered potential ways to block neurodegeneration. Our research outcomes have Group Leader Professor John Shine AO FAA significant clinical implications for the lives of people who confront devastating _ Dr Nicola Lee completed her PhD neurodegenerative diseases. studies and also received the 'Roger Neural stem cells can be isolated from the adult olfactory neuroepithelium (situated Melick Young Investigator Award', at in the nose) and grown in the laboratory in the form of olfactory neurospheres. Pituitary Research Group the joint IBMS/ANZBMS Scientific These structures are three-dimensional aggregates of cells that are able to grow Group Leader Professor Ken Ho Meeting, in Sydney. into neuronal and non-neuronal cells. The identity of the cell type within the olfactory neuroepithelium that gives rise to these neural stem cells remains elusive. The pituitary gland produces key hormones that control body growth, strength, _ Professor Ken Ho was awarded an Our group studies the basic biology of adult olfactory stem cells with the aim of appetite, metabolism, mood and reproduction under the control of the brain. An Honorary Fellowship of the Royal identifying, isolating and propagating these cells, and to determine the conditions over or under active pituitary gland can lead to a range of diseases from dwarfism in College of Physicians, London. He has needed to transform them into the different types of nerve cells found in the brain, children to infertility, mood disorders, muscle wasting, obesity and diabetes in been invited to serve on the Annual for example, those lost in Parkinson's or Alzheimer's disease. adults. A major focus is on understanding how the brain controls body metabolism, Steering Committee of the US composition and physical function through pituitary hormones. These effects Endocrine Society for three years. Eating Disorders Research underlie many key health problems such as obesity, osteoporosis and sarcopaenia Group Leaders Professor Herbert Herzog and Associate Professor Amanda (muscle wasting). _ Dr Paul Lee won the 2009 Young Sainsbury-Salis Investigator Award of the Internal Projects include the investigation of the sympathetic nervous system (SNS) in the Medicine Society of Australia and New One of our laboratory's major goals is to understand how appetite and body weight control of body fat and muscle. One aspect looks at the metabolic consequences of Zealand; the Bryan Hudson Clinical are regulated. Defects in the brain pathways that regulate these processes may be beta-blockers, which are a class of drugs commonly used to treat blood pressure. Endocrinology Award of the Endocrine responsible for causing wasting conditions such as anorexia nervosa and cancer Society of Australia; and a Travel cachexia as well as the metabolic resistance to weight loss occurring in overweight Complementary work in the laboratory addresses the cellular and molecular Award from the Pituitary Society. or obese people. mechanisms by which sex steroids modify the action of growth hormone and seeks to identify novel growth hormone regulated genes. _ Dr Vita Birzniece received the Women Our main focus is on neuropeptide Y (NPY) and its Y-receptors, since many of the in Endocrinology Young Investigator molecules that regulate appetite and body weight do so via this system. Our research Another project aims to develop new approaches for the detection of growth Award of the US Endocrine Society; findings have implications for the treatment of obesity, infertility, poor lactation, hormone doping and for studying the effects of growth hormone on performance. the Australasian Branch of Women in dwarfism, and osteoporosis, as well as anorexia nervosa and cancer cachexia. Endocrinology Novo Nordisk New Investigator Travel Award of the Endocrine Society of Australia; and a Travel Award from the Pituitary Society. Osteoporosis & Bone Biology Program OSTEOPOROSIS & BONE BIOLOGY PROGRAM ...... LEADER Professor John A Eisman AO 49

Program Overview

Osteoporosis affects the capacity for independent living and also contributes to premature mortality for men and women, younger and older. As prevention is the best strategy for reducing this large human and financial burden, we need to improve our knowledge of the risk factors for fracture; find ways to better assess treatments; increase our understanding of bone biology and help identify new treatment possibilities.

Program Highlights collaborations using genome wide analysis advanced technology. _ Demonstrated the association between fragility fracture and _ Demonstrated the frequency of premature mortality in both old and vitamin D insufficiency in general younger men and in women. populations and in severely ill individuals in hospital. These findings _ Extended our prognostic models for suggest that vitamin D deficiency predicting fracture risk for men and contributes to in-hospital mortality. women, implemented in www.fractureriskcalculator.com, _ Demonstrated that neurotransmitters widely used by doctors and patients in the brain play a critical role in the worldwide. regulation of bone mass, a function that has been considered purely _ Validated our nomograms for absolute mechanical. Specifically, neuropeptide fragility fracture risk in collaboration Y (NPY) directly controls the cells that with colleagues in Canadian make bone, increasing bone mass in Multicentre Osteoporosis Study line with body weight. (CaMOS) data. Similar collaborations are underway with the Geelong _ Identified the ability of bone cells to Osteoporosis Study (Melbourne), fine tune the brain's signals at a local CAIFOS study (Perth) and other major level, increasing bone mass in parts of cohorts in New Zealand, Norway, UK the body exposed to greater weight, and Holland. or load.

_ Reported findings of initial clinical studies _ Initiated collaboration with a group in with a novel treatment that reduces Strasbourg to study the action of bone breakdown, and which has major endorphin receptors in the control of potential in osteoporosis treatment. bone mass.

_ Identified novel chromosomal regions _ Developed a collaborative relationship that harbor osteoporosis genes in the at Royal North Shore Hospital to world's first search for osteoporosis investigate the role of NPY in genes, as part of international osteoarthritis.

Professor John Eisman OSTEOPOROSIS & BONE BIOLOGY PROGRAM OSTEOPOROSIS & BONE BIOLOGY PROGRAM ...... 50 51

Left: Professor Tuan Nguyen and Bich Tran

_ Dr Nguyen Nguyen won The Research Groups Left: Dr Paul Baldock People Highlights and Ayse Zengin Outstanding Abstract Award of the _ The Bone Biology Group received an 2009 ANZBMS annual meeting. Population, Individual and Genetic Determinants of Osteoporotic Fracture Risk Right: Iris Wong NHMRC project grant for the 5th and their Outcomes consecutive year. The current application _ Bone Program students had the Group leaders Professor Tuan Nguyen and Associate Professor Jackie Center is to investigate the interaction following successes: Bich Tran, the between sex steroids and neural ASBMR Christine & T Jack Martin The Dubbo Osteoporosis Epidemiology Study (DOES), which began in 1989, is the pathways in the control of bone mass. Research Travel Grant; Iris Wong, a world's longest running large-scale epidemiological study of osteoporotic fractures Young Investigator Award at the in men and women. The data from this study has allowed us to develop powerful _ Professor Tuan Nguyen collaborated ASBMR Annual Scientific Meeting, predictive models to identify men and women at high risk of fracture, who would with colleagues at the Pham Ngoc Denver, USA; and Dana Bliuc, the benefit most from preventative interventions. Our search for new osteoporosis genes Thach University of Medicine, Ho Chi Stuart Furler Travel Award to attend is continuing in large-scale international collaborations. We are developing tools to Minh City (Vietnam) to examine the the ASBMR Scientific Meeting. Young predict those at high (and low) risk for osteoporosis and fractures. This insight will effect of vegetarian diets and researchers Dr Frank Driessler and direct the focus of preventative activities on osteoporosis or other health concerns, micronutrients on bone health. He is Dr Nguyen Nguyen and students as most appropriate. Establishing how clinical factors and genetic factors interact to also working to help them design new Bich Tran and Iris Wong were awarded affect bone biology will help identify those individuals who would most benefit from studies on the effects of vitamin D on a Qantas Travel Grant each for 2009. existing therapies, as well as helping to identify targets for novel therapies. bone health and infectious diseases. Bone Biology _ Professor John Eisman chaired the Group Leader Dr Paul Baldock development group for Guidelines for Osteoporosis Management, supported Osteoporosis is characterised by a reduction in bone density and therefore strength. by the Federal Department of Health It is caused by an imbalance between bone production and bone loss. Our group's through the Royal Australian College research is primarily focused upon investigating the influence of brain signals on of General Practitioners. The final bone formation and strength. Much of this work makes use of transgenic mouse draft is with the NHMRC at present. models and is carried out in collaboration with researchers in the Neuroscience Program. Our investigations involving the effect of neurotransmitter neuropeptide Y _ Dr Paul Baldock gave the Plenary (NPY) have identified a novel and powerful pathway for stimulating the production Symposium of the 2009 annual of bone and increasing bone strength, suggesting an approach to new treatment. conference of the American Society of Recent work has identified major interactions between the NPY pathway and body Bone and Mineral Research in Denver weight and responses to stress. Colorado. He also gave a Plenary Symposium Presentation at the 41st Fracture Prevention — Clinical Studies International Symposium on Group Leader Professor John Eisman AO Endocrinology & Metabolism in Prague. He was an invited oral Our clinical studies group continues to participate in multicentre international clinical presenter at the International Pituitary trials evaluating potential osteoporosis treatments that are in the final stages of Society meeting in Washington. pharmaceutical development. Involvement in these studies helps ensure we remain at the cutting edge of knowledge of novel therapies and provides an entry pathway to pharmaceutical interest in our novel developments. Core Research Facilities ...... 53

Technology is an important component of being competitive in medical science. Garvan's core research facilities contain state-of- the-art equipment that enables our scientists to perform the necessary experiments to understand disease processes better. Highly trained managers oversee the facilities which are also available to external researchers.

Australian BioResources (ABR) facility, based in Moss Vale, holds mouse production colonies under clean room conditions for Garvan and other medical research organisations in NSW. Services offered include the import and export of mice, rederivation and embryo freezing.The Biological Testing Facility, located at Garvan in Darlinghurst, receives mice from ABR for holding in specialised experimental zones to enable quality animal-based research.

Australian Cancer Research Foundation (ACRF) Unit for the Molecular Genetics of Cancer houses equipment that can detect and analyse genomic variations such as gene losses, mutations, expression, and methylation on a large scale. Diverse platforms are available for facilitating research within and outside Garvan. The facility strives to achieve high-throughput, sensitivity, accuracy and cost effectiveness. In addition to sequencing and methylation analysis services, there is now a mouse genotyping service available for all researchers in NSW.

Australian BioResources Management Highlights CORE RESEARCH FACILITIES ...... 54 CHIEF OPERATING OFFICER Mr John Dakin 55

Gene Chip Facility contains the Affymetrix Microarray System that is used to _ Completed the legal, operational and _ Provided office facilities at Garvan for compare the levels of gene transcripts in tissue samples. Output helps researchers logistical work for The Kinghorn Research Australia from July 2009. find potential genes of interest, the subsets of which can then be further analysed Cancer Centre, our proposed Research Australia is a member-based in the ACRF Unit that can handle large numbers of samples. Garvan was the first in translational cancer research centre advocacy organisation with a mission Australia to establish the system. (currently under construction). to make health and medical research a national priority. Clinical Research Facility is a unique resource dedicated to the conduct of research _ Integrated the St Vincent's Hospital in people. It provides a vital interface between discoveries in the laboratory and their Diabetes Centre into the Garvan _ Executed Service Level Agreements evaluation in humans. The facility, staffed by highly skilled nurses and clinical building. governing shared essential services for investigators, has a range of support services and state-of the art equipment to Medical Research Institutes within the evaluate new therapies. _ Completed the first full year of St Vincent's Research Precinct. The operations at the Australian Agreements cover stores and dock, Peter Wills Bioinformatics Centre applies techniques derived from disciplines such BioResources (ABR) facility. Within waste, medical gases, bulk gases, as applied mathematics, statistics and computer science to understand, organise and that time ABR reached 50% of total generators, media prep, glass wash analyse biological data. This includes the housing of both clinical and microarray data, capacity (25,000 mice); completed and cryogenics. and the building of computer programs for querying and analysing these datasets. rederivation for lines from partner Examples of these programs include Cansto for managing clinical cancer data and institutes; introduced DNA preparation _ Established a Precinct Occupational Stuart for animal records management. CanSto is used across Australia by the and embryo cyropreservation services; Health and Safety (OHS) Committee Australian Prostate Cancer Collaboration for all their clinical information management. Above: Seema Bhalla and started supplying commonly used to enable a co-ordinated and aligned Garvan's caArray server houses microarray experiment results for researchers across Right: David Keenan inbred strains to Garvan and partner approach for OHS management. archive, already the biggest in Australia. Australia and connects them to the (US) National Cancer Institute's cancer internet, institutes. The facility now holds all This library of information allows us to known as caBIG (Cancer Biomedical Informatics Grid). The software tool, GenePattern, major breeding colonies for Garvan _ Signed an MOU between Garvan and compare the genes of cancer patients enables users to access their data from caArray and analyse it themselves. and seven partner institutes and Sydney Water allowing the two with the genes of healthy people. constitutes a significant resource for businesses to co-operate in water MLC Community Foundation Flow Facility provides cell analysis and cell sorting biomedical research in NSW. saving initiatives. Water consumption _ Implemented a new $250,000 file services to members of the St Vincent's Research Precinct and external users across has already been significantly reduced. server, using the very latest Sydney. The facility houses two cell sorters and five flow cytometry analysers, and _ Worked closely with Illawarra TAFE to technology as used by medical will expand further in size and capability as new facility space opens at the produce the first distance formatted _ Maintained a downward trend in our research facilities around the world. beginning of 2010. Flow Cytometry is a technology that allows simultaneous Certificate III Animal Technology monthly electricity usage, with a The server stores the huge volume of analysis of the physical, biochemical and molecular characteristics of single cells or course in NSW. This will support the reduction of 20% compared to the data collected each day on Garvan's particles suspended in a fluid stream. Cell analysis and sorting are frequently used to development of technical staff corresponding months of 2008. research instruments: Microscope identify the various cell types present in biological tissues and to determine their manning the ABR facility. images as well as flow cytometry, developmental or functional relationships. It has wide-ranging applications in _ Installed LED (light emitting diode) genomic, mass spectrometry and immunology, haematology, infectious diseases and cancer. The facility is supported _ Completely refurbished laboratories in lighting in public areas of Garvan, such human genome sequence data. by a generous grant from MLC. one of seven levels at Garvan. Air as the foyer, resulting in energy conditioning units were overhauled; savings for those areas of around _ Delivered a computer solution to Pieter Huveneers Molecular Imaging Facility consists of a number of state-of- automatic doors fitted; gas isolation 90%. These findings will have a direct implement the Bone Program's web- the-art microscopes which, using a variety of fluorescence based techniques, are zones put in place; efficient light impact on the type of fittings to be based fracture risk calculator. capable of imaging tissue, cells, intracellular organelles and even multiple individual fittings and occupancy sensors installed in any future works and may molecules in live cells. Using techniques such as Total Internal Reflection Fluorescence installed; anti-microbial paint used; also be useful in determining the type _ Won a Computer World Honors (TIRF) microscopy we are able to image events occurring on or near the surface of a and many of the original fittings (such of fittings to be used in The Kinghorn award for the Garvan IT Group's cell. Using laser scanning confocal microscopy we can precisely image 'slices' of as lab benches and sinks) recycled. Cancer Centre. delivery of world-class research samples which can be reconstructed into a 3D representation for analysis. These The Master Builders Association information systems. provide our scientists with the best possible means of identifying where and when recognised the excellence of the work _ Received a bioinformatics molecules of interest are in normal tissue and how this may differ in disease. with a Merit Award in their category infrastructure grant from the Cancer of Interior Fitouts up to $5,000,000. Institute NSW to extend our microarray Business Development ...... 57

Overview Business Development Advisory Council The Business Development team engages with the pharmaceutical and biotech sector and partners with other academic organisations to The Business Development Advisory take Garvan's research discoveries one step closer towards the Council (BDAC) includes several representatives from the biotech and development of new treatments and diagnostic tests. pharmaceutical industries. 2009 members included: Working closely with Garvan scientists, the Business Development team is responsible for all aspects of commercialisation from Dr Lisa McIntyre (Chair) monitoring research activities to maximising early capture of Director, LEK Consulting intellectual property, identifying pharma/biotech market Professor John Shine AO FAA opportunities, and negotiating and managing commercial agreements. Executive Director, Garvan Importantly, the Business Development team establishes applied collaborations with organisations who have additional technologies Dr George Moore which greatly increase the potential for Garvan's breakthroughs to be External Director developed for clinical use. Dr Merilyn Sleigh External Director The Garvan patent portfolio comprises 27 patent families covering treatment, diagnostics and screening categories. Peter Carre CEO, Burrill Australia

G2 Therapies and Novo Nordisk Christina Hardy Director, Business Development G2 Therapies is a private company, chaired by Dr John Schubert, which develops & Legal Affairs, Garvan and commercialises antibody-based therapeutics for inflammation. Founded at Garvan in 2002, major investors include AMWIN and Baron Nominees. John Dakin Chief Operating Officer, Garvan In early 2006, G2 announced the signing of a major research, development and licensing agreement with Danish healthcare company Novo Nordisk to develop an anti-C5aR antibody. The Anti-C5aR antibody treatment, currently in clinical trials, holds promise for a number of inflammatory conditions including lupus, rheumatoid arthritis and other autoimmune diseases. Garvan Community GARVAN COMMUNITY ...... 59

Life Governors Partners for the Future WJ and PA McNamara Garvan Supporters Mr Norman Brunsdon Mrs Mabs Melville Mrs Kate Buchanan Allind Pty Limited Mrs Margaret Adams Mr John & Mrs Mary Miller A W Edwards Pty Ltd Mr L Bulla Amadeus Energy Limited Dr W. Michael Baker John K Moody Abey Family Foundation Burwood RSL Club Ltd Mr John Armati Ms James Belger Miss Helen Morgan Accenture BVN Architecture Australian Cancer Research Foundation Mr Peter Binnie Mary and Herbert Morris ADA Viertel Award Mr & Mrs W & G M Bylhouwer Australian Stock Exchange Ltd Ken Bloxsom Mr Peter Olive Mr C R Adamson Mrs Helen Callander ASX-Reuters Charity Foundation Linda Booth Mr & Mrs Lloyd & Joan Poulton AGL Energy Limited Cancer Australia The Blundy Family Mr Earle & Mrs Marlene Boutwell Mrs Lesley Powell Michael Ahrens Cancer Council NSW Coca-Cola Amatil Mr Alan & Mrs Anne Boyle Mr George Quigg Mr Ian Ainsworth Cancer Institute NSW Mr Charles P Curran AC Dr William R Bradford Mrs Judy Radecki Mr Len Ainsworth Mr Tony Carlton The Curran Foundation Bernard & Barbara Brown Kathy Rockwell Alcoa Foundation Castle Harlan Inc Lady Mary Fairfax AC OBE Ken & Betty Brown Tanya Roddan Ms Helen-Lea Alexopoulos CHAMP Private Equity Ferris Family Foundation Mrs Diana Bryers In memory of Sonia Gabrielle Saba-Losey Alliance for Lupus Research (US) CHAMP Ventures Mr Laurence S Freedman AM Mrs Judith Clark Miss Vi Saint Alma Hazel Eddy Trust Mr Chris Chapman & Dr Cath Chapman Miss Felicia D Garvan Mrs Madeline Coelho Mrs Pamela Salmon Amadeus Energy Limited Mr Craig Chapman Trevor and Christina Kennedy Mr James Patrick Garvan & Family Mr Rodney F Darke Ms Coral Saunders AMP Foundation Mr Stephen & Mrs Molly Charlesworth Mr & Mrs B & A Ginges Cristine Davison Miss Thelma Shepherd Mr Neil Anderson Dr Daniel Christ Mr Matthew Ellis Mr William Gruy Ms J Del Layton Ms Colleen Sheppard Arjuna Pty Ltd Cochlear Limited Mr Robert Emerson Mr Paul & Mrs Judy Hennessy Mrs Marlene Dixon Mrs D Silva Ascham School Colin Biggers & Paisley Mr David Ephraums HIH Insurance Mr John Dobies Mrs Cynthia Southwell Mr Martin Ash The Corio Foundation Ernest Heine Family Foundation and Mr Pieter H Huveneers Ms Daile Falconer Mr & Mrs Peter Sturrock The Australian Ladies Variety The Council of The City of Orange Mrs Janice Gibson Mrs Virginia Kahlbetzer Mr Gabriel & Mrs Joan Farago Mr Leonard Towers Association Inc Brett & Susan Courtenay Mr Eric and Mrs Patricia Farley Mr T Kennedy AM & Mrs C Kennedy Ms Jan Foster Mr & Mrs Eric & Pauline Vail Australian Research Council Craig Mostyn & Co Pty Ltd Ferris Family Foundation Mr Ralph & Mrs Lorraine Keyes Mr Michael & Mrs Joy Foulsham Mrs Judith Wheeldon AM Australian Rotary Health CSR Limited Mr Ronald Ficarra The Kinghorn Foundation Elizabeth Fyffe Mrs Jean Whittaker Australian Securities & Investments The Curran Foundation Mrs Margaret Fitzpatrick Mrs Mabs Melville Miss Flo Greene Ms Faye Margaret Williams Commission Mr Nick Curtis Mr Roger Fitzsimmons The Mirvac Group Mr & Mrs William & Jacqueline Goodyear Miss June Yuen Australian Securities Exchange Mr & Mrs R Cusick Ms Jane Forster & Mr Glenn Eggleton MLC Community Foundation Mrs Jean B Hale Bain & Company Mr & Mrs Kamlesh & Swati Dave Mr Michael & Mrs Joy Foulsham National Australia Bank Ltd Mr Ron Hardaker Volunteers Mr Peter Baines Professor J G & Dr J R Davis Foundation for Prader-Willi Research Dr Graham O’Neill Dr Bronia Hatfield Ms Lorna Baird Mr & Mrs Tony & Coleen De Saxe Mr John A Fraser The Order of the Eastern Star Chapter Ms Heather Patricia Hindle Mrs Janet Barkell Professor Antony Basten Delta Electricity Judith Fritz No. 38 Mr J K L Hooton Mrs Deirdre Blakemore Bathurst Cathedral Parish Department of Foreign Affairs and Trade Mr Sunny Fung The Paramor Family Byram & Deborah Johnston Mr Graham Curtis Mr Douglas Battersby Diabetes Australia Research Trust Elizabeth Fyffe Mr K Packer AC Mrs Florence Jones Ms Margarita Field Bendigo and Adelaide Bank Limited Mr & Mrs Daryl & Kate Dixon Eric & Tonia Gale George Patterson Pty Ltd Mrs Virginia Kahlbetzer Miss Lyndie Hemery Mrs Marie Bennett Geoff and Dawn Dixon Mr Justin H Gardener The Petre Foundation Mr Bob Kijurina Ms Lynne Jones BHP Billiton Community Program Ms Rochelle Dizon Mr & Mrs John & Sue Garner The Lady Proud Foundation Ms Lili Koch Mrs Juliet Kirkpatrick Mrs Kaye Blaiklock Mrs Bette Dolman Ms Lynette Gearing The Ritchie Family Roberta Lauchlan and Barry Thompson Mrs Janice Lee BNP Paribas Mr Matthew Donnelly Ms Belinda Gibson Mr Tim & Mrs Sally Sims Mr Gottfried Lausegger Mr John McInerney Mrs Thelma Susan Bonner Mr J Doyle Mr G Giles Mr Robert Strauss MBE Ms Mary Lawson Miss Sarah McKechnie Mrs D Bonser Mrs Joan Doyle GlaxoSmithKline Mr Laurie Sutton Mr Keith Line Mr Bob Neilson Mr G Bradley Dunstan Family Foundation John Glennie Dr John Tonkin Mrs Adell Littlejohn Mrs Joan Neilson Mr Brendan James Brady Ms Carol Durkin Cherie Glick and family for Joe Westfield Holdings Ltd Ms Maria Lydaki Mrs Jean Pushong Breast Cancer Australia Mr Phil Durney Mr Cyril Golding EJ Whitten Foundation Dr Norman Marshall Mrs Julie Reid Brenton Marriot & Associates Pty Ltd Mr Andrew Eger Mrs Elizabeth Goldsmith Doreen Martin Mr Bill Upton Drs Ruth and Desmond Bright Elaine Haworth Charitable Gift Fund Ms Delta Goodrem Mr Desmond J McCarthy Mrs Eileen Vesey Ken & Betty Brown Mr W A B Elder Mr & Mrs William & Jacqueline Goodyear GARVAN COMMUNITY GARVAN COMMUNITY ...... 60 61

Gorokan-Kanwal Lions Club Mr & Ms Keith & Judith Kay Mr & Mrs David Milman RAAF Association St George Branch Miss Alison Stephen graysonline.com Mr & Mrs Patrick & Beryl Keane Mr & Mrs Doug & Eveline Milne Incorporated Ms Joyce Strong The Greatorex Foundation Mrs Helen Keir Mr Frank Mitchell Clive and Vera Ramaciotti (NSW) Ms May Sukari Sharon Green Professor Geoffrey Kellerman AO MLC Community Foundation Foundation Dr Rahul Suri Ms Elizabeth Grenfell Mr T Kennedy AM & Mrs C Kennedy Geoff & Jan Moles Mrs E Ramsden Professor Rob Sutherland FAA Gresham Partners Limited Mr Ralph and Mrs Lorraine Keyes Mr & Mrs David & Renata Money Mr Roy Randall Mr Laurie Sutton Mrs Enid Griffin Mr Bob Kijurina Mr & Mrs Simon & Catriona Mordant Mr Ian Rank Mr Nick Tait OBE & Mrs Mimi Tait Griffith Hack Mr W Bruce Kirkpatrick & Mrs L Moroney Rebecca L Cooper Foundation Mr Harry Tamvakeras William A and Laura H Gruy Mrs Juliet Kirkpatrick Motor Neurone Disease Research Mr Jean Redman Thyne Reid Foundation Gynaecological Oncology (GO) Mrs Ruth Kistars Institute Brad & Lisa Rees Mr & Mrs Joe & Pat Tripodi Research Fund Mrs Zoe Kominatos Mr Peter Murphy Retire@Ease Financial Planning Tusa Pty Ltd H Kallinikos Pty Limited L & H Payne Medical Research National Breast Cancer Foundation Mr John Richards Mrs A Udy Mrs Jean B Hale Charitable Foundation National Health and Medical Research Mr George Risk UNSW Jill and John Kinghorn Hallidays Heating & Cooling Ms Josie La Spina Council Mrs Judy Roach Mr Peter Unwin Mrs Ann Hanson The Lady Proud Foundation Netherlands Cancer Society Ms Sylvia Robson Mr Ian Vale Bequests Mr H Harries In Memory of Michael Ison Large Mr Alon Nir The Rodney & Judith O'Neil Foundation Ms Kay Vernon Ms Betty Haugh Ms Helen Lee Mr Robert Nixon Carol and Steve Rogers Memorial Vida Rees Foundation Pty Ltd Estate of the Late Gloria M Backhus Mr & Mrs Bill & Alison Hayward Mrs P Lee Mrs Lavinia Nolan Charity Day Vittoria Coffee Estate of the Late Margaret Benning HCF Australia - In memory of Mr Robert Leece AM RFD Novartis Pharmaceuticals Australia Rosemary Pryor Foundation John & Megan Wade Estate of the Late Elena M Bucovaz Greg Gardiner Mr Jeff Leibovici NSW Ministry for Science and Mr Bruce Rosenberg Wade Civil Engineering Pty Ltd Estate of the Late Denzil de Ferrars Hearing and Balance Centre Mrs Linda Leupen Medical Research Mr Lance Rosenberg Mrs Caroline Walder Carrington Heliflite Pty Limited The Lions Club of Berowra Inc. NSW State Government Spinal Cord Ms Kelly Rosmain Mrs Nikki Warburton Estate of the Late Lynette A Frankel Meredith Hellicar Lions Club of Hawkesbury Bells Line Inc. and Related Neurological Diseases Roth Charitable Foundation Dr JR Warneford Estate of the Late Alan Hellicar Mr Paul Hillary Mr Michael Lowe Grants Program Rothschild Australia Limited Dr & Mrs Gary & Ms Winfred Warner Estate of the Late Margaret E Kenny Mr Lionel Hirning Ms Maria Lydaki NSW Women's Bowling Association Inc. Royal Australasian College of Surgeons Mr Max Watt Estate of the Late Kevin P Maguire Dr Robin Holliday Ms Helen Lynch AM Mr Michael O'Dea RT Hall Trust Ms Alexandra Wedutenko Estate of the Late Wesselina Miller Mr I Holmes Mrs Ann Macintosh Michael and Marianne O'Dea Mr Nathan Ryan Ms Deanne Weir Estate of the Late Betty M Noble Dr & Mrs Francis & Marie Hooper Macquarie Golden 'A' Club Mr J O'Farrell Mr Martin Sachs Mrs Judith Wheeldon AM Estate of the Late Florence A O'Sullivan Mr J K L Hooton Macquarie Group Foundation Dr G S Oldfield Sanofi-Aventis Mr Robert White Estate of the Late Helen M Parr Mrs Jessica Hore Mr D & Mrs K Magarey Mr Anthony Olivier Dr Timothy Schmidt Mr Alan Whitfield Estate of the Late Ronald M Pfeiffer Mrs Sue Howieson Mallesons Stephen Jaques Dr Graham O'Neill Mr Laurie W Seaman E J Whitten Foundation Estate of the Late Elaine E Pope Howland-Rose Foundation Manildra Group of Companies Order of the Eastern Star Chapter No. 67 Mr Graham See J O and J R Wicking Trust Estate of the Late Joyce M Roarty Mr Richard Humphry Mr R & Mrs S Maple-Brown Pace Foundation Pty Ltd Mr & Mrs T & J Shanahan In Memory of the Late Kathrin Nell Estate of the Late Babette J Ryan Stanley Hunt OAM Marathon Pty Limited Pacific Equity Partners Walter and Edith Sheldon A Wilshire Estate of the Late George W Steed Ms Belinda Hutchinson Marshall Family Foundation Miss Winnie Pang Mr David Shmith Witchery Mr Pieter H Huveneers Doreen Martin Greg & Kerry Paramor Skilled Group Ann and Peter Wolstenholme Insurance Marketing Group of The Hon John & Mrs Dympna Matthews Ian Paul Skin Cancer Specialists Wood Family Foundation Australia Pty Ltd Mr Murray McGain Perpetual Foundation - G & C Bradley Skipper-Jacobs Charitable Trust Mr & Mrs JL and BJ Woodward IPC Network Services (Australia) Pty Ltd Peter McGovern Foundation Joseph Skrzynski AO & Roslyn Horin Mr J & Mrs L Woolf Mr Peter Ivany McMahon Refrigeration and Perpetual Trustees Mr M Slavich Estate of the Late Olga Mabel Woolger The Hon Justice Peter M. Jacobson Airconditioning Pty Ltd Arvid & Karen Petersen Mr Graham Smith World Anti-Doping Agency (WADA) Mr R Jarvis WJ and PA McNamara Pinpoint Pty Ltd Mrs Jennifer M Smith XLP Research Trust (UK) John Lamble Foundation Medisure Indemnity Australia Pty Ltd Mr V John Plummer Mr Barry Smorgon Mr Ralph W Young The Juvenile Diabetes Research Mrs Mabs Melville Poly Industries & Poly Tooling Pty Ltd Mr Ezekiel Solomon Mr Stanley Young Foundation (JDRF) Merck Sharp & Dohme (Aust) Pty Limited Premier Media Group Mr & Mrs David & Audrey Solomons Mr Joseph E Zaresky Mrs Virginia Kahlbetzer Mr John Mesley Prostate Cancer Centre, St Vincent’s Mr Neil Spitzer Dr Colleen Kane The Michael & Andrew Buxton Hospital St Vincent's & Holy Spirit Health Lady Catherine Kater AM Foundation Prostate Cancer Foundation of Australia St Vincent’s Clinic Foundation Governance ...... 63

Garvan Institute Board and a former National Managing Partner of Blake Dawson. Mr Bradley was Chairman of the Bill Ferris AC Garvan Research Foundation and a Director of Chairman the Garvan Institute Board from 1999-2009. Nominated by the Trustees of St Vincent's Hospital Bill Ferris AC Nicholas Curtis Mr Bill Ferris is Executive Chairman of the Nominated by the Trustees of St Vincent's Hospital CHAMP Private Equity Group, one of Australia's leading private capital groups, providing venture Mr Nicholas Curtis has a background in capital, expansion capital, and management investment banking and the resources industry. buyout funding in Australasia. Mr Ferris is He is Executive Chairman of Lynas Corporation Chairman of the Health and Hospitals Fund Limited, an Australian public company specialising Advisory Board as part of the Federal in Rare Earths. Mr Curtis served as Chairman of Martin Hoffman Government's Nation-Building Funds initiative. the Board of St Vincents & Mater Health Sydney Former directorships include: Chairman, from August 2004 to October 2009 and is a Australian Trade Commission (Austrade), Austar Director of St Vincent's Health Australia Ltd and United Communications Limited, and Bradken St Vincent's Healthcare Ltd. Resources Pty Ltd. Mr Ferris is also a Director of the Garvan Research Foundation. Mr Ferris was Geoff Dixon made an Officer in the Order of Australia in Nominated by the Garvan Research Foundation 1990 for services to the export industry and in 2008 was made Companion in the Order of Mr Geoff Dixon held the position of Managing Graham J Bradley AM Australia for his philanthropic activities and his Director and Chief Executive of Qantas Airways role in the establishment of the private equity Limited from 2000-2008. After joining Qantas sector in Australia. in 1994 he was appointed Deputy Chief Executive in 1998 and then to the Board of Martin Hoffman Directors in 2000. Treasurer Nominated by the Sisters of Charity Mr Dixon currently sits on the boards of publicly listed Australian companies, Crown Limited and Nicholas Curtis Mr Martin Hoffman is a First Assistant Secretary Consolidated Media Holdings Limited. He is in the Department of the Prime Minister & Chairman of the Queensland (Australia) Major Cabinet in Canberra. He is Head of the Office of Events Corporation and Deputy Chairman of the Coordinator General which is responsible for Tourism Australia. He also sits on the Board of implementing the Nation Building - Economic The Great Barrier Reef Foundation, and the Stimulus Plan, and he also coordinates from Advisory Board of Seabury Aviation & Aerospace, Prime Minister & Cabinet's perspective a number New York. of major Government projects including the Geoff Dixon National Broadband Network. He previously had a John Horvath AO lengthy career in digital media and technology, Nominated by the Federal Minister for Health including as CEO of NineMSN, Australia's largest internet media company. He has also held senior Professor John Horvath was the Australian management roles with Fairfax Media and Optus. Government Chief Medical Officer from 2003- 2009. He is currently continuing to advise the Graham J Bradley AM Department of Health & Ageing and the School Nominated by the Garvan Research Foundation of Medicine, University of Sydney, and holds the

John Horvath AO position of Honorary Professor of Medicine. Mr Graham Bradley is a professional company Professor Horvath is currently a member of director. Mr Bradley is Chairman of Stockland Council of the NHMRC and Chairman of the Corporation Limited, HSBC Bank Australia Limited Healthcare Committee. He is a Fellow of the and Anglo American Australia Limited. From Royal Australasian College of Physicians and is a 1995 to 2003 he was Managing Director of distinguished practitioner, researcher and teacher. Perpetual Limited. He is a former Partner of Professor Horvath was previously Clinical McKinsey & Company, management consultants, Professor of Medicine at University of Sydney GOVERNANCE GOVERNANCE ...... 64 65

and a specialist renal physician at Royal Prince Mirvac between 2004 and 2008. Greg is a past American Bar Association, the New York Bar recent Inquiry into Vietnam Veterans Cancer Alfred Hospital (RPAH), and Area Director of President of the Property Council of Australia and Association and the California Bar Association. Incidence and Mortality. Professor Smith is Renal Services for the RPAH and Concord past President of Investment Funds Association, Warren is admitted as a solicitor in New South currently a Director of SV&MHS, NewSouth Repatriation General Hospitals. He is also known a Fellow of the Australian Property Institute and Wales and as a lawyer in New York and California. Innovations, and a number of other research as a leader in a range of medical training and The Royal Institute of Chartered Surveyors. Greg centres and institutes. Anne Keating workforce organisations. He is also a former is a director of a number of not-for-profit Jillian Segal AM Jillian Segal AM President of the Australian Medical Council and organisations and is also a board member of the Nominated by the UNSW Bernadette Tobin the NSW Medical Board. Sydney Swans and LJ Hooker. Nominated by the Trustees of St Vincent's Hospital Ms Jillian Segal is a Director of the National Anne Keating Sister Carol Pedersen RSC Australia Bank and the Australian Securities Associate Professor Bernadette Tobin is Director Nominated by the NSW Minister for Health Nominated by the Sisters of Charity Exchange Limited. She is also Deputy Chancellor of the Plunkett Centre for Ethics at St Vincent's of the UNSW and involved with a number of Hospital, Sydney, and Reader in Philosophy at the Ms Anne Keating is a company director and holds Sister Carol Pedersen graduated as a trained other community not-for-profit organisations, Australian Catholic University. Dr Tobin is

Lisa McIntyre board positions in a range of industries including nurse at St Vincent's Sydney in 1963 and is a John Shine AO FAA including the General Sir John Monash Honorary Ethicist at the Children's Hospital at advertising, banking, and property. She is on the Sister of Charity. She holds a PhD from UNSW Foundation. Ms Segal has had a career in law, Westmead, Honorary Associate Professor in the boards of the Goodman Group Limited, Ardent and a BSW (Hons 1) from the same institution. regulation, governance and policy development. Faculty of Medicine at the University of Sydney, Leisure Group Limited and STW Communications She also holds an Advanced Diploma from the Formally she was President of the Administrative and Conjoint Associate Professor in the School of Group Limited. Ms Keating is also a member of Sydney College of Homoeopathic Medicine, and Review Council and Chair of the Banking and Medicine at UNSW. She served for three triennia the Advisory Council of RBS Group (Australia), has completed postgraduate work, obtaining an Financial Services Ombudsman Board. From on the Australian Health Ethics Committee, a Governor of the Cerebral Palsy Foundation and Associate Diploma in Advanced Homoeopathic 1997-2002, Ms Segal was a Commissioner of principal committee of the NHMRC. She also Trustee of the Centennial Parklands and Moore Medicine. For over 20 years Sr Carol was a the Australian Securities and Investments chaired the drafting group, which prepared the Park Trust. Her former boards include Insurance member of various human research ethics Commission (ASIC), being Deputy Chair from first Code of Ethics for Catholic Health and Aged Greg Paramor Peter J Smith Australia Group Limited, NRMA Limited, the committees, and was active at national, state 2000-2002. Prior to joining ASIC, Ms Segal was Care Services in Australia. WorkCover Authority of NSW, the Tourism Task and local levels in the development of Alcohol a corporate lawyer specialising in corporate and Force and was an inaugural Director at the Victor and Drug Services. environmental law, having been a partner at Allen Ronald Trent Chang Cardiac Research Institute. Ms Keating Allen & Hemsley. Nominated by the Federal Minister for Health was the General Manager, Australia for United Steven Rubic Airlines from 1993-2001. Nominated by the Sisters of Charity John Shine AO FAA Professor Ronald Trent is Professor of Molecular Appointed by the Garvan Institute Board Genetics, University of Sydney and Head of the Lisa McIntyre Steven Rubic was appointed CEO of St Vincents Department of Molecular and Clinical Genetics, Sister Carol Pedersen RSC Nominated by the Federal Minister for Health & Mater Health Sydney (SV&MHS) in April Bernadette Tobin Professor John Shine is Executive Director of the Royal Prince Alfred Hospital. He is the Chairman 2008. Prior to this he was Executive Director of Garvan Institute of Medical Research and a board of the Advisory Committee for the University's Dr Lisa McIntyre is a partner with the strategy St Vincent's Private Hospital a position he held member of the Garvan Research Foundation. He recently formed Forensic Medicine & Science consulting firm LEK Consulting and head of LEK's since 1997. He is currently a Board Member of is Professor of Molecular Biology and Professor Network. He was a member of the NHMRC Asia Pacific Life Sciences and Health Care SV&MHS, the Health Industry (Superannuation) of Medicine at the UNSW, and a director of many Research Committee from 1997-2009 and has practice. She has over 18 years consulting Plan, the Garvan Research Foundation, a member scientific, research and medical bodies been Chairman of the NHMRC Human Genetics experience for the biotechnology and healthcare of Australian Commission on Safety and Quality throughout Australia, including the recent ex- Advisory Committee as well as a member of the sector and has worked with over 100 different Health Care (Private Hospital Sector Committee) Chairman of the National Health and Medical NHMRC Council since 2006. Professor Trent Steven Rubic biotechnology and life sciences and healthcare and is a past Chairman of the NSW Private Ronald Trent Research Council (NHMRC) and until 2006 a discontinued his role as Director in February 2009. clients. Dr McIntyre relocated to Sydney in 2002 Hospitals Association. He has completed an MBA member of the Prime Minister's Science, after nine years in the United States co-heading and is a Fellow of the Australian Institute of Engineering & Innovation Council (PMSEIC). LEK's Life Sciences practice where she advised Company Directors. many of the world's leading biotechnology and Peter Smith speciality pharmaceutical companies. Warren Scott Nominated by the UNSW Nominated by the NSW Minister for Health Greg Paramor Professor Peter Smith is Dean, Faculty of

Warren Scott Nominated by the Garvan Research Foundation Mr Warren Scott is the General Counsel of the Medicine, UNSW. He specialised in cancer Australian Prudential Regulation Authority and a medicine and research following study in Mr Greg Paramor is a founding Partner of Equity former Director and the General Counsel of Australia, USA and Germany. He has held senior Real Estate Partners. Greg has been involved in Citigroup in Australia. He was formerly the hospital management posts in Brisbane and the real estate and funds management industry Chairman of the Woolcock Institute of Medical Melbourne, and senior academic appointments at for more than 35 years, and was the co-founder Research, as well as a delegate to the Australian the Universities of Queensland, Melbourne and of Growth Equities Mutual, Paladin Australia and American Leadership Dialogue. He is a member Auckland. He has served in a consulting role to the James Fielding Group. Greg was the CEO of of the Law Society of New South Wales, the Government, including as Chairman of the GOVERNANCE GOVERNANCE ...... 66 67

Garvan Research Foundation Jane Allen Alec Brennan Bill Ferris AC

Geoff Dixon Ms Jane Allen is a Partner in Egon Zehnder Mr Alec Brennan pursues a portfolio of business Mr Bill Ferris is Executive Chairman of the Chairman from April 2009 International's (EZI) Sydney office, where she and not for profit interests. Until March 2007, CHAMP Private Equity Group, one of Australia's focuses on chief executive officer and board he was Chief Executive Officer and Managing leading private capital groups, providing venture Geoff Dixon Mr Geoff Dixon held the position of Managing appointments. Ms Allen has been at Egon Alec Brennan Director of CSR Limited. He is Chairman of capital, expansion capital and management Director and Chief Executive of Qantas Airways Zehnder International for 10 years and has publicly listed Emeco Limited, Chairman and co- buyout funding in Australasia. Mr Ferris is Limited from 2000-2008. After joining Qantas consulted with corporate boards and companies investor in privately owned PPI Limited and Chairman of the Garvan Institute of Medical in 1994 he was appointed Deputy Chief of all sizes. In addition to a number of speaking Chairman of Tomago Aluminium Pty Ltd. He is a Research and Chairman of the Health and Executive in 1998 and then to the Board of engagements, Ms Allen has had a number of Fellow of the Senate of the University of Sydney Hospitals Fund Advisory Board as part of the Directors in 2000. articles published on CEO succession and and Chair of several of its committees. Mr Federal Government's Nation-Building Funds diversity at the executive and board level. She Brennan joined the Foundation Board in 2000. initiative. Former directorships include: Chairman, Mr Dixon currently sits on the boards of publicly currently leads a number of global strategy Australian Trade Commission (Austrade), Austar

Graham J Bradley AM listed Australian companies, Crown Limited and initiatives roles for one of the firm's core client Melinda Conrad Melinda Conrad United Communications Limited and Bradken Consolidated Media Holdings Limited. He is practices. Previously she has been Managing Resources Pty Ltd. Mr Ferris was made an Chairman of the Queensland (Australia) Major Partner of the Sydney office and co-leader of Ms Melinda Conrad is a consultant and company Officer in the Order of Australia in 1990 for Events Corporation and Deputy Chairman of the Australian Practice as well as Head of the director for a range of business, health, and services to the export industry and in 2008 was Tourism Australia. He also sits on the Board of Consumer Products Practice Group for Asia community organisations. In addition to the made Companion in the Order of Australia for his The Great Barrier Reef Foundation, Advisory Pacific. She is currently a member of Chief Garvan, she serves as a non-executive director philanthropic activities and his role in the Board of Seabury Aviation & Aerospace, New Executive Women, a small active network of for the Australia New Zealand Breast Cancer Trial establishment of the private equity sector in York, and the Garvan Institute. He joined the Australia's top women leaders. Prior to joining Group and the Australian Brandenburg Orchestra. Australia. Mr Ferris joined the Foundation Board Foundation Board in 2009 Egon Zehnder International she worked at Ms Conrad has extensive experience in strategy, in 2001. Jane Allen Gabriel Farago Procter & Gamble in sales and then marketing in marketing and business development. In her Graham J Bradley AM both the US and Australia. Ms Allen has an MBA previous executive career, she founded and ran Lyn Gearing Chairman to April 2009 from Harvard Business School and a Bachelor of the retail store chain, Conrads Warehouse, and Arts from Smith College. Ms Allen joined the held management roles at Harvard Business Ms Lyn Gearing was appointed to the Garvan Mr Graham Bradley is a professional company Foundation Board in 2007. School and Colgate-Palmolive. Ms Conrad joined Foundation Board as a representative of the director. Mr Bradley is Chairman of Stockland the Foundation Board in September 2003. Sisters of Charity. Ms Gearing was a Director of Corporation Limited, HSBC Bank Australia Limited Stockland Corporation Limited up until December and Anglo American Australia Limited. From Gabriel Farago 2008 and is currently a Director of Queensland 1995 to 2003 he was Managing Director of Bill Ferris AC Investment Corporation Limited, Hancock Natural Perpetual Limited. He is a former partner of Mr Gabriel Farago is a company director and Resource Group Australasia Pty Limited, IMB McKinsey & Company, management consultants, consultant advising corporations on litigation Limited and two other not for profit and a former national managing partner of Blake management. Prior to establishing his organisations. Ms Gearing was the Chief Dawson. Mr Bradley was Chairman of the consultancy, he practised as a solicitor and Executive Officer of the NSW State Garvan Research Foundation and a Director of barrister for over 30 years, specialising in Superannuation schemes from 1997 to 2002, the Garvan Institute Board from 1999-2009. commercial disputes both in Australia and and has substantial experience in superannuation, overseas. Mr Farago has extensive business funds management, corporate finance and Lyn Gearing interests, and has been involved in property management consulting. Ms Gearing joined the development for more than 20 years. A passion Foundation Board in 2005. for philanthropic and charitable causes also reaches back many years, and in 1984 he was made a member of the Knightly Order of Vitez. Mr Farago joined the Foundation Board in 2008. GOVERNANCE GOVERNANCE ...... 68 69

Loftus Harris AM John Landerer CBE AM Sister Paulina Pilkington RSC AM John Shine AO FAA

Mr Loftus Harris is a non-executive director on Mr John Landerer is a solicitor specialising in Sister Paulina has a broad background in health Professor John Shine is Executive Director of the various boards in NSW, Victoria and Queensland, corporate advisory work and is also a policy formation, having been a member of the Garvan Institute of Medical Research and a board a National Chairman of the Australian Institute of professional company director. He is currently Hospitals and Health Services Commission (Sax member of the Garvan Institute Board of Loftus Harris AM Export, and holds the appointment of Special Chairman of Goldsearch Limited and other Sr Paulina Pilkington RSC AM Commission) and Assistant Director General, Directors. He is Professor of Molecular Biology Trade Representative to the Middle East and private companies. He has served as Chairman of Nursing Branch, Federal Department of Health. and Professor of Medicine at the UNSW, and a India for the Queensland Government. He the Home Purchase Assistance Authority and is Sister Paulina resigned from the Garvan Institute director of many scientific, research and medical previously held chief executive positions in the on the Board of Life Education Australia and the Board in February 2000 and has been a member bodies throughout Australia, including the recent NSW and Queensland public sectors with Royal Institute for Deaf and Blind Children as well of the Foundation Board since 1994. ex-Chairman of the National Health and Medical responsibility for whole-of-Government activities as on the boards of various charitable Research Council (NHMRC) and until 2006 a including international trade, investment, institutions. Mr Landerer was appointed a Visiting Brad Rees member of the Prime Minister's Science, innovation, business, and regional development. Professor at Macquarie University in Business Engineering & Innovation Council (PMSEIC).

John Landerer CBE AM He also served extensively overseas as an and Commercial Law and holds an honorary Brad Rees Mr Brad Rees is involved in a number of Australian Trade Commissioner. Mr Harris joined doctorate from that university. He is also a charitable, arts and educational interests and is a Karim Temsamani the Foundation Board in 2008. Fellow of University of Sydney. Mr Landerer is a director of a private investment company. Until Member of the Order of Australia and a 2007, he was a Managing Director and Equity Mr Karim Temsamani manages Google's domestic Byram Johnston OAM Commander of the Most Excellent Order of the Partner of the investment banking firm Goldman business and strategic partnerships in Australia British Empire. He is also a Commander in the Sachs JBWere. Mr Rees was with the firm for 23 and New Zealand. Karim joined Google from Mr Byram Johnston is the Chief Executive Officer Order of the Star of Italian Solidarity. He joined years and worked in the Melbourne, Sydney and Fairfax Media, where he was most recently of MainstreamBPO, a company providing back the Board in 2007. London offices providing financial and investment Group Director, Fairfax General Magazines office processing and administration services to banking advice to corporations and governments (responsible for growing the profile and Bryram Jonston OAM Steven Rubic fund managers and superannuation funds. Prior Simon Mordant in Australia and overseas. Mr Rees joined the advertising revenue of Fairfax's suite of inserted to establishing this business he spent over 30 Foundation Board in 2008. magazines) and Commercial Director for years as a management consultant. He serves Mr Simon Mordant is a co-founder and joint Newspapers (responsible for agency and group on the board of a number of companies. Mr Chief Executive of Caliburn Partnership, a leading Steven Rubic sales, trade marketing and business development). Johnston joined the Foundation Board in 1997. independent corporate advisory firm specialising Prior to this he was the publisher and Vice in advising major corporates on their merger and Mr Steven Rubic was appointed Chief Executive President of Who Weekly at Time Inc South John Koch acquisition and capital markets strategies. He is a Officer of St Vincents & Mater Health Sydney Pacific from 1999-2002. He has previously chartered accountant and is Chair of the (SV&MHS) in April 2008. Prior to this he was served in a variety of senior capacities with John Koch Mr John Koch is Chief Representative of the Museum of Contemporary Art Foundation and a John Shine AO FAA Executive Director of St Vincent's Private Hachette, including the positions of Regional Hong Kong based Forma Group of Companies, a director of the Sydney Theatre Company. Mr Hospital a position he held since 1997. He is Business Publisher in Hong Kong (1995-96), former board member of St Vincent's Hospital Mordant joined the Foundation Board in 2009. currently a Board Member of SV&MHS, the Associate Publisher for Korea in Seoul (1996- and Chair of its Finance Committee. He is also Health Industry (Superannuation) Plan, the 97), and Managing Director for Hachette in the former Chair of Woods Cottage Foundation, Garvan Institute, a member of Australian Sydney (1997-99). Mr Temsamani joined the which assists intellectually disabled young adults. Commission on Safety and Quality Health Care Foundation Board in 2008. He had a 32-year career with the Commonwealth (Private Hospital Sector Committee) and is a Bank assuming a range of domestic and past Chairman of the NSW Private Hospitals Simon Mordant international responsibilities. Mr Koch joined the Karim Temsamani Association. He has completed an MBA and is a Foundation Board in 2000. Fellow of the Australian Institute of Company Directors. Mr Rubic joined the Foundation Board in 2008. Publications ...... 71

tumourigenic and pro-metastatic and Birzniece V, Sata A, Ho KK. Growth A associated with extracapsular spread in hormone receptor modulators. Rev ...... advanced prostate cancer. Br J Cancer Endocr Metab Disord 2009; 10:145-56. Abdipranoto-Cowley A, Park JS, 2009; 100:1784-93. Croucher D, Daniel J, Henshall S, Bjornerem A, Johnsen SL, Nguyen TV, Galbraith S, Mervin K, Vissel B. Activin A Baldock PA, Lee NJ, Driessler F, Lin S, Kiserud T, Seeman E. The shifting is essential for neurogenesis following Allison S, Stehrer B, Lin EJ, Zhang L, trajectory of growth in femur length neurodegeneration. Stem Cells 2009; Enriquez RF, Wong IP, McDonald MM, during gestation. J Bone Miner Res 27:1330-46. During M, Pierroz DD, Slack K, Shi YC, Epub 2009/11/26. Yulyaningsih E, Aljanova A, Little DG, Agrawal L, Maxwell CR, Peters PJ, Ferrari SL, Sainsbury A, Eisman JA, Bliuc D, Nguyen ND, Milch VE, Nguyen Clapham PR, Liu SM, Mackay CR, Herzog H. Neuropeptide Y knockout TV, Eisman JA, Center JR. Mortality risk Strayer DS. Complexity in human mice reveal a central role of NPY in the associated with low-trauma immunodeficiency virus type 1 (HIV-1) coordination of bone mass to body osteoporotic fracture and subsequent co-receptor usage: roles of CCR3 and weight. PLoS ONE 2009; 4:e8415. fracture in men and women. Jama CCR5 in HIV-1 infection of monocyte- 2009; 301:513-21. derived macrophages and brain microglia. Bennett HL, Brummer T, Timpson P, J Gen Virol 2009; 90:710-22. Patterson KI, Daly RJ. Signalling by EGF Bluestone JA, Mackay CR, O'Shea JJ, receptor in human cancers: Accentuate Stockinger B. The functional plasticity of Akhtar N, Marlow R, Lambert E, the positive, eliminate the negative. In: T cell subsets. Nat Rev Immunol 2009; Schatzmann F, Lowe ET, Cheung J, Katz Haley JD, Gullick WJ, editors. EGFR 9:811-6. E, Li W, Wu C, Dedhar S, Naylor MJ, Signaling Networks in Cancer Therapy: Streuli CH. Molecular dissection of Humana Press; 2009. p. 224-244. Bogaerts S, Clements JD, Sullivan JM, integrin signalling proteins in the control Oleskevich S. Automated threshold of mammary epithelial development and Bhandari M, Thomas AC, Hussey DJ, Li detection for auditory brainstem differentiation. Development 2009; X, Jaya SP, Woods CM, Schloithe AC, responses: comparison with visual 136:1019-27. Mayne GC, Carati CJ, Toouli J, Ormandy estimation in a stem cell transplantation CJ, Saccone GT. Galanin mediates the study. BMC Neurosci 2009; 10:104. Alles MC, Gardiner-Garden M, Nott DJ, pathogenesis of cerulein-induced acute Wang Y, Foekens JA, Sutherland RL, pancreatitis in the mouse. Pancreas Bohm M, Locke WJ, Sutherland RL, Musgrove EA, Ormandy CJ. Meta- Epub 2009/12/05. Kench JG, Henshall SM. A role for GATA- analysis and gene set enrichment 2 in transition to an aggressive relative to er status reveal elevated Biankin AV, Kench JG, Colvin EK, Segara phenotype in prostate cancer through activity of MYC and E2F in the "basal" D, Scarlett CJ, Nguyen NQ, Chang DK, modulation of key androgen-regulated breast cancer subgroup. PLoS ONE Morey AL, Lee CS, Pinese M, Kuo SC, genes. Oncogene 2009; 28:3847-56. 2009; 4:e4710. Susanto JM, Cosman PH, Lindeman GJ, Visvader JE, Nguyen TV, Merrett ND, Bone HG, McClung MR, Roux C, Recker Allison SJ, Baldock PA, Enriquez RF, Lin Warusavitarne J, Musgrove EA, Henshall RR, Eisman JA, Verbruggen N, Hustad E, During M, Gardiner EM, Eisman JA, SM, Sutherland RL. Expression of CM, Dasilva C, Santora AC, Ince BA. Sainsbury A, Herzog H. Critical interplay S100A2 calcium-binding protein Odanacatib, a Cathepsin-K Inhibitor for between neuropeptide Y and sex steroid predicts response to pancreatectomy Osteoporosis: A two-year study in pathways in bone and adipose tissue for pancreatic cancer. Gastroenterology postmenopausal women with low bone homeostasis. J Bone Miner Res 2009; 2009; 137:558-68, 568 e1-11. density. J Bone Miner Res Epub 24:294-304. 2009/10/31. Birzniece V, Meinhardt UJ, Handelsman DJ, Ho KK. Testosterone stimulates Boyman O, Letourneau S, Krieg C, B extra-hepatic but not hepatic fat Sprent J. Homeostatic proliferation and ...... oxidation (Fox): comparison of oral and survival of naive and memory T cells. Balanathan P, Williams ED, Wang H, transdermal testosterone administration Eur J Immunol 2009; 39:2088-94. Pedersen JS, Horvath LG, Achen MG, in hypopituitary men. Clin Endocrinol Stacker SA, Risbridger GP. Elevated level (Oxf) 2009; 71:715-21. Bruce CR, Hoy AJ, Turner N, Watt MJ, of inhibin-alpha subunit is pro- Allen TL, Carpenter K, Cooney GJ, PUBLICATIONS PUBLICATIONS ...... 72 73

Febbraio MA, Kraegen EW. Chang DK, Johns AL, Merrett ND, Gill differentiation: lessons from the Hegarty BD, Turner N, Cooney GJ, Overexpression of carnitine AJ, Colvin EK, Scarlett CJ, Nguyen NQ, spectrum of resulting infections. Int E G Kraegen EW. Insulin resistance and fuel ...... palmitoyltransferase-1 in skeletal Leong RW, Cosman PH, Kelly MI, Immunol 2009; 21:1003-11. homeostasis: the role of AMP-activated muscle is sufficient to enhance fatty Sutherland RL, Henshall SM, Kench JG, Edelsbrunner ME, Herzog H, Holzer P. Gatto D, Paus D, Basten A, Mackay CR, protein kinase. Acta Physiol (Oxf) acid oxidation and improve high-fat Biankin AV. Margin clearance and Cooper WA, Kohonen-Corish MR, Evidence from knockout mice that Brink R. Guidance of B cells by the 2009; 196:129-45. diet-induced insulin resistance. Diabetes outcome in resected pancreatic cancer. McCaughan B, Kennedy C, Sutherland peptide YY and neuropeptide Y enforce orphan G protein-coupled receptor EBI2 2009; 58:550-8. J Clin Oncol 2009; 27:2855-62. RL, Lee CS. Expression and prognostic murine locomotion, exploration and shapes humoral immune responses. significance of cyclin B1 and cyclin A in ingestive behaviour in a circadian cycle- Immunity 2009; 31:259-269. H ...... Brummer T. B-Raf signaling. In: Schwab Chang DK, Nguyen NQ, Merrett ND, non-small cell lung cancer. and gender-dependent manner. Behav M, editor. Encyclopedia of Cancer. 2nd Dixson H, Leong RW, Biankin AV. Role of Histopathology 2009; 55:28-36. Brain Res 2009; 203:97-107. Gelmann EP, Henshall SM. Clinically Hinshelwood RA, Melki JR, Huschtscha ed: Humana Press; 2009. endoscopic ultrasound in pancreatic relevant prognostic markers for prostate LI, Paul C, Song JZ, Stirzaker C, Reddel cancer. Expert Rev Gastroenterol Cox SL, Silveira PA. Emerging roles for Edelsbrunner ME, Painsipp E, Herzog H, cancer: the search goes on. Ann Intern RR, Clark SJ. Aberrant de novo Hepatol 2009; 3:293-303. B-lymphocytes in type 1 diabetes. Holzer P. Evidence from knockout mice Med 2009; 150:647-9. methylation of the p16INK4A CpG C Expert Review of Clinical Immunology for distinct implications of island is initiated post gene silencing in ...... Cheng KK, Iglesias MA, Lam KS, Wang Y, 2009; 5:311-324. neuropeptide-Y Y2 and Y4 receptors in Gill AJ, Johns AL, Eckstein R, Samra JS, association with chromatin remodelling Caldon CE, Sergio CM, Schutte J, Sweeney G, Zhu W, Vanhoutte PM, the circadian control of locomotion, Kaufman A, Chang DK, Merrett ND, and mimics nucleosome positioning. Boersma MN, Sutherland RL, Carroll JS, Kraegen EW, Xu A. APPL1 potentiates Crowe S, Wu LE, Economou C, Turpin exploration, water and food intake. Cosman PH, Smith RC, Biankin AV, Hum Mol Genet 2009; 18:3098-109. Musgrove EA. Estrogen regulation of insulin-mediated inhibition of hepatic SM, Matzaris M, Hoehn KL, Hevener Neuropeptides 2009; 43:491-7. Kench JG. Synoptic reporting improves cyclin E2 requires cyclin D1 but not c- glucose production and alleviates AL, James DE, Duh EJ, Watt MJ. histopathological assessment of Ho-Pham LT, Nguyen ND, Nguyen TV. Myc. Mol Cell Biol 2009; 29:4623-39. diabetes via Akt activation in mice. Cell Pigment epithelium-derived factor Ewald DP, Eisman JA, Ewald BD, pancreatic resection specimens. Effect of vegetarian diets on bone mineral Metab 2009; 9:417-27. contributes to insulin resistance in Winzenberg TM, Seibel MJ, Ebeling PR, Pathology 2009; 41:161-7. density: a Bayesian meta-analysis. Am J Calmy A, Fux CA, Norris R, Vallier N, obesity. Cell Metab 2009; 10:40-7. Flicker LA, Nash PT. Population rates of Clin Nutr 2009; 90:943-50. Delhumeau C, Samaras K, Hesse K, Cheung NW, Conn JJ, d'Emden MC, bone densitometry use in Australia, Gitler AD, Chesi A, Geddie ML, Hirschel B, Cooper DA, Carr A. Low Gunton JE, Jenkins AJ, Ross GP, Sinha Czernichow S, Lee CM, Barzi F, 2001-2005, by sex and rural versus Strathearn KE, Hamamichi S, Hill KJ, Ho-Pham LT, Nguyen ND, Vu BQ, Pham bone mineral density, renal dysfunction, AK, Andrikopoulos S, Colagiuri S, Twigg Greenfield JR, Baur LA, Chalmers J, urban location. Med J Aust 2009; Caldwell KA, Caldwell GA, Cooper AA, HN, Nguyen TV. Prevalence and risk and fracture risk in HIV infection: a SM. Position statement of the Australian Woodward M, Huxley RR. Efficacy of 190:126-8. Rochet JC, Lindquist S. Alpha-synuclein factors of radiographic vertebral cross-sectional study. J Infect Dis Diabetes Society: individualisation of weight loss drugs on obesity and is part of a diverse and highly conserved fracture in postmenopausal Vietnamese 2009; 200:1746-54. glycated haemoglobin targets for adults cardiovascular risk factors in obese interaction network that includes PARK9 women. Bone 2009; 45:213-7. with diabetes mellitus. Med J Aust adolescents: a meta-analysis of F and manganese toxicity. Nat Genet ...... Cantley J, Burchfield JG, Pearson GL, 2009; 191:339-44. randomized controlled trials. Obes Rev 2009; 41:308-15. Ho-Pham LT, Nguyen PL, Le TT, Doan Schmitz-Peiffer C, Leitges M, Biden TJ. 2009; 11:150-158. Frangioudakis G, Burchfield JG, TA, Tran NT, Le TA, Nguyen TV. Veganism, Deletion of PKCepsilon selectively Chung L, Nelson AE, Ho KK, Baxter RC. Narasimhan S, Cooney GJ, Leitges M, Goenaga D, Hampe C, Carre N, Cailliau bone mineral density, and body enhances the amplifying pathways of Proteomic profiling of growth hormone- Biden TJ, Schmitz-Peiffer C. Diverse K, Browaeys-Poly E, Perdereau D, Holt composition: a study in Buddhist nuns. glucose-stimulated insulin secretion via responsive proteins in human peripheral D LJ, Daly RJ, Girard J, Broutin I, Issad T, Osteoporos Int 2009; 20:2087-2093...... roles for protein kinase C delta and increased lipolysis in mouse beta-cells. blood leukocytes. J Clin Endocrinol protein kinase C epsilon in the Burnol AF. Molecular determinants of Diabetes 2009; 58:1826-34. Metab 2009; 94:3038-43. Daniel JA, Galbraith S, Iacovitti L, generation of high-fat-diet-induced Grb14-mediated inhibition of insulin Hoehn KL, Salmon AB, Hohnen-Behrens Abdipranoto A, Vissel B. Functional glucose intolerance in mice: regulation signaling. Mol Endocrinol 2009; C, Turner N, Hoy AJ, Maghzal GJ, Cazzolli R, Huang P, Teng S, Hughes WE. Comstock CE, Augello MA, Benito RP, heterogeneity at dopamine release sites. of lipogenesis by protein kinase C delta. 23:1043-51. Stocker R, Van Remmen H, Kraegen EW, Measuring phospholipase D activity in Karch J, Tran TH, Utama FE, Tindall EA, J Neurosci 2009; 29:14670-80. Diabetologia 2009; 52:2616. Cooney GJ, Richardson AR, James DE. insulin-secreting pancreatic beta-cells Wang Y, Burd CJ, Groh EM, Hoang HN, Good KL, Avery DT, Tangye SG. Resting Insulin resistance is a cellular antioxidant and insulin-responsive muscle cells and Giles GG, Severi G, Hayes VM, Das A, Wilson R, Biankin AV, Merrett Frost SA, Nguyen ND, Center JR, Eisman human memory B cells are intrinsically defense mechanism. Proc Natl Acad Sci adipocytes. Methods Mol Biol 2009; Henderson BE, Le Marchand L, Kolonel ND. Surgical therapy for gastrointestinal JA, Nguyen TV. Timing of repeat BMD programmed for enhanced survival and U S A 2009; 106:17787-92. 462:241-51. LN, Haiman CA, Baffa R, Gomella LG, stromal tumours of the upper measurements: development of an responsiveness to diverse stimuli Knudsen ES, Rui H, Henshall SM, gastrointestinal tract. J Gastrointest absolute risk-based prognostic model. J compared to naive B cells. J Immunol Holt LJ, Lyons RJ, Ryan AS, Beale SM, Chan TD, Gatto D, Wood K, Camidge T, Sutherland RL, Knudsen KE. Cyclin D1 Surg 2009; 13:1220-5. Bone Miner Res 2009; 24:1800-7. 2009; 182:890-901. Ward A, Cooney GJ, Daly RJ. Dual Basten A, Brink R. Antigen affinity splice variants: polymorphism, risk, and ablation of Grb10 and Grb14 in mice controls rapid T-dependent antibody isoform-specific regulation in prostate Dudgeon K, Famm K, Christ D. Fulcher DA, Avery DT, Fewings NL, Graham SJ, Black MJ, Soboloff J, Gill DL, reveals their combined role in regulation production by driving the expansion cancer. Clin Cancer Res 2009; Sequence determinants of protein Berglund LJ, Wong S, Riminton DS, Dziadek MA, Johnstone LS. Stim1, an of insulin signaling and glucose rather than the differentiation or 15:5338-49. aggregation in human VH domains. Adelstein S, Tangye SG. Invariant natural endoplasmic reticulum Ca2+ sensor, homeostasis. Mol Endocrinol 2009; extrafollicular migration of early Protein Eng Des Sel 2009; 22:217-20. killer (iNK) T cell deficiency in patients negatively regulates 3T3-L1 pre- 23:1406-1414. plasmablasts. J Immunol 2009; Cook MC, Tangye SG. Primary immune with common variable immunodeficiency. adipocyte differentiation. 183:3139-49. deficiencies affecting lymphocyte Clin Exp Immunol 2009; 157:365-9. Differentiation 2009; 77:239-47. PUBLICATIONS PUBLICATIONS ...... 74 75

Hoy AJ, Brandon AE, Turner N, Watt MJ, in muscle: Influence of exercise- Lee P, Greenfield JR, Campbell LV. Lee P, Samaras K, Glanville AR, Center susceptibility locus on chromosome Bruce CR, Cooney GJ, Kraegen EW. Lipid activated pathways in vitro and obesity Managing young people with Type 1 JR. Transplant recipients on the edge of M 15q25-26. Mol Psychiatry 2009; ...... and insulin infusion-induced skeletal in vivo. Biochim Biophys Acta 2009; diabetes in a 'rave' new world: metabolic the hypocalcemia abyss. J Heart Lung 14:492-500. muscle insulin resistance is likely due to 1792:777-82. complications of substance abuse in Transplant 2009; 28:93-5. Ma CS, Suryani S, Avery DT, Chan A, metabolic feedback and not changes in Type 1 diabetes. Diabet Med 2009; Nanan R, Santner-Nanan B, Deenick EK, McCormack AI, McDonald KL, Gill AJ, IRS-1, Akt, or AS160 phosphorylation. Kidney Disease: Improving Global 26:328-33. Lee P, Sevastos J, Campbell LV. Tangye SG. Early commitment of naive Clark SJ, Burt MG, Campbell KA, Braund Am J Physiol Endocrinol Metab 2009; Outcomes (KDIGO) CKD-MBD Work Surviving calciphylaxis. J Bone Miner human CD4(+) T cells to the T follicular WJ, Little NS, Cook RJ, Grossman AB, 297:E67-75. Group. KDIGO clinical practice guideline Lee P, Greenfield JR, Campbell LV. Metab 2009; 27:247-50. helper (T(FH)) cell lineage is induced by Robinson BG, Clifton-Bligh RJ. Low O6- for the diagnosis, evaluation, prevention, Vitamin D insufficiency—a novel IL-12. Immunol Cell Biol 2009; methylguanine-DNA methyltransferase Hubert FX, Kinkel SA, Crewther PE, and treatment of chronic kidney mechanism of statin-induced myalgia? Lefevre M, Redman LM, Heilbronn LK, 87:590-600. (MGMT) expression and response to Cannon PZF, Webster KE, Link M, Uibo disease-mineral and bone disorder Clin Endocrinol (Oxf) 2009; 71:154-5. Smith JV, Martin CK, Rood JC, temozolomide in aggressive pituitary R, O'Bryan MK, Meager A, Forehan SP, (CKD-MBD) Kidney Int 2009; Greenway FL, Williamson DA, Smith SR, Ma CS, Tangye SG. Helping the helpers! tumours. Clin Endocrinol (Oxf) 2009; Smyth GK, Mittaz L, Antonarakis SE, 76:(Suppl 13). Lee P, Greenfield JR, Center JR, Ravussin E. Caloric restriction alone and Immunity 2009; 31:12-4. 71:226-33. Peterson P, Heath WR, Scott HS. Aire- Campbell LV. Plasma insulin with exercise improves CVD risk in Deficient C57BL/6 mice mimicking the King C. New insights into the concentration is useful to guide glucose healthy non-obese individuals. Mackay CR. Ethical considerations of McGuire HM, Vogelzang A, Hill N, common human 13-base pair deletion differentiation and function of T supplement in insulin overdose. Atherosclerosis 2009; 203:206-13. live case transmissions. JACC Flodstrom-Tullberg M, Sprent J, King C. mutation present with only a mild follicular helper cells. Nat Rev Immunol Intensive Care Med 2009; 35:181-2. Cardiovasc Interv 2009; 2:892-3. Loss of parity between IL-2 and IL-21 autoimmune phenotype. Journal of 2009; 9:757-66. Leong GM, Kee AJ, Millard SM, Martel in the NOD Idd3 locus. Proc Natl Acad Immunology 2009; 182:3902-3918. Lee P, Greenfield JR, Day RO, Ho KK. N, Eriksson N, Turner N, Cooney GJ, Mainra R, Elder G. Review article: Sci USA 2009; 106:19438-19443. Kondo T, El Khattabi I, Nishimura W, Weight maintenance in hospitalized Hardeman EC, Muscat GE. The Ski Managing bone complications after Hui X, Zhu W, Wang Y, Lam KS, Zhang J, Laybutt DR, Geraldes P, Shah S, King G, geriatric patients treated with beta- proto-oncogene regulates body kidney transplantation. Nephrology Melmed S, Colao A, Barkan A, Molitch Wu D, Kraegen EW, Li Y, Xu A. Major Bonner-Weir S, Weir G, Sharma A. p38 blockers. J Am Geriatr Soc 2009; composition and suppresses lipogenesis. (Carlton) 2009; 14:437-42. M, Grossman AB, Kleinberg D, urinary protein-1 increases energy MAPK is a major regulator of MafA 57:1125-6. Int J Obes (Lond) Epub 2009/12/24. Clemmons D, Chanson P, Laws E, expenditure and improves glucose protein stability under oxidative stress. Marino E, Villanueva J, Walters S, Schlechte J, Vance ML, Ho K, Giustina A. intolerance through enhancing Mol Endocrinol 2009; 23:1281-90. Lee P, Greenfield JR, Ho KK. Factors Lin S, Shi YC, Yulyaningsih E, Aljanova A, Liuwantara D, Mackay F, Grey ST. Guidelines for acromegaly management: mitochondrial function in skeletal muscle determining inadequate hypoglycaemia Zhang L, Macia L, Nguyen AD, Lin EJ, CD4(+)CD25(+) T-cells control an update. J Clin Endocrinol Metab of diabetic mice. J Biol Chem 2009; Kraegen EW, Bruce C, Hegarty BD, Ye during insulin tolerance testing (ITT) During MJ, Herzog H, Sainsbury A. autoimmunity in the absence of B-cells. 2009; 94:1509-17. 284:14050-7. JM, Turner N, Cooney G. AMP-activated after pituitary surgery. Clin Endocrinol Critical role of arcuate Y4 receptors and Diabetes 2009; 58:1568-77. protein kinase and muscle insulin (Oxf) 2009; 71:82-5. the melanocortin system in pancreatic Menzies KK, Lee HJ, Lefevre C, resistance. Front Biosci 2009; polypeptide-induced reduction in food Maslowski KM, Vieira AT, Ng A, Kranich Ormandy CJ, Macmillan KL, Nicholas KR. I 14:4658-72. Lee P, Greenfield JR, Seibel MJ, Eisman intake in mice. PLoS ONE 2009; Insulin, a key regulator of hormone ...... J, Sierro F, Yu D, Schilter HC, Rolph MS, JA, Center JR. Adequacy of vitamin D 4:e8488. Mackay F, Artis D, Xavier RJ, Teixeira responsive milk protein synthesis during Igwe JC, Jiang X, Paic F, Ma L, Adams replacement in severe deficiency is MM, Mackay CR. Regulation of lactogenesis in murine mammary DJ, Baldock PA, Pilbeam CC, Kalajzic I. L dependent on body mass index. Am J Linterman MA, Rigby RJ, Wong R, Silva explants. Funct Integr Genomics Epub ...... inflammatory responses by gut Neuropeptide Y is expressed by Med 2009; 122:1056-60. D, Withers D, Anderson G, Verma NK, microbiota and chemoattractant 2009/10/16. osteocytes and can inhibit osteoblastic Lee NJ, Herzog H. NPY regulation of Brink R, Hutloff A, Goodnow CC, receptor GPR43. Nature 2009; activity. J Cell Biochem 2009; bone remodelling. Neuropeptides 2009; Lee P, Ho KK. Therapy: Growth hormone Vinuesa CG. Roquin differentiates the 461:1282-6. Merrett ND, Wilson RB, Cosman P, 108:621-30. 43:457-63. supplementation: a silver lining for the specialized functions of duplicated T cell Biankin AV. Superior mesenteric artery aged? Nat Rev Endocrinol 2009; costimulatory receptor genes CD28 and Mayor R, Casadome L, Azuara D, syndrome: diagnosis and treatment Lee P, Campbell LV. Vitamin D 5:424-5. ICOS. Immunity 2009; 30:228-41. Moreno V, Clark SJ, Capella G, Peinado strategies. J Gastrointest Surg 2009; J deficiency: the invisible accomplice of 13:287-92...... MA. Long-range epigenetic silencing at metabolic endotoxemia? Curr Pharm Lee P, Ho KK, Fulham MJ. The Linterman MA, Rigby RJ, Wong RK, Yu 2q14.2 affects most human colorectal Joshi D, Center JR, Eisman JA. Des 2009; 15:2751-8. importance of brown adipose tissue. N D, Brink R, Cannons JL, Schwartzberg cancers and may have application as a Millar EK, Anderson LR, McNeil CM, Investigation of incidental Engl J Med 2009; 361:418; author PL, Cook MC, Walters GD, Vinuesa CG. non-invasive biomarker of disease. Br J O'Toole SA, Pinese M, Crea P, Morey AL, hypercalcaemia. BMJ 2009; Lee P, Eisman JA, Center JR. Vitamin D reply 419-20. Follicular helper T cells are required for Cancer 2009; 100:1534-9. Biankin AV, Henshall SM, Musgrove EA, 339:b4613. deficiency in critically ill patients. N Engl systemic autoimmunity. J Exp Med Sutherland RL, Butt AJ. BAG-1 predicts J Med 2009; 360:1912-4. Lee P, Nair P, Eisman JA, Center JR. 2009; 206:561-76. McAuley EZ, Blair IP, Liu Z, Fullerton JM, patient outcome and tamoxifen Vitamin D deficiency in the intensive Scimone A, Van Herten M, Evans MR, responsiveness in ER-positive invasive K Lee P, Greenfield JR. 25- care unit: an invisible accomplice to Lopez JA, Burchfield JG, Blair DH, Mele ductal carcinoma of the breast. Br J ...... Kirkby KC, Donald JA, Mitchell PB, Hydroxyvitamin d and risk of stroke: morbidity and mortality? Intensive Care K, Ng Y, Vallotton P, James DE, Hughes Schofield PR. A genome screen of 35 Cancer 2009; 100:123-33. Kanzleiter T, Wilks D, Preston E, Ye J, possible mediation by statin therapy? Med 2009; 35:2028-32. WE. Identification of a distal GLUT4 bipolar affective disorder pedigrees Frangioudakis G, Cooney GJ. Regulation Stroke 2009; 40:e35; author reply trafficking event controlled by actin provides significant evidence for a of the nuclear hormone receptor nur77 e37-8. polymerization. Mol Biol Cell 2009; 20:3918-29. PUBLICATIONS PUBLICATIONS ...... 76 77

Millar EK, Dean JL, McNeil CM, O'Toole Eisman JA, El-Hajj Fuleihan G, Josse RG, Nguyen NK, Sartori SB, Herzog H, Tasan Cochrane Database Syst Rev mortality in older adults: the Health, SA, Henshall SM, Tran T, Lin J, Quong A, Lips P, Morales-Torres J. Global vitamin R, Sperk G, Singewald N. Effect of 2009:CD005633. Aging, and Body Composition Study. S ...... Comstock CE, Witkiewicz A, Musgrove D status and determinants of neuropeptide-Y Y2 receptor deletion on Diabetologia 2009; 52:591-5. EA, Rui H, Lemarchand L, Setiawan VW, hypovitaminosis D. Osteoporos Int emotional stress-induced neuronal Palmer SC, McGregor DO, Craig JC, Samaras K. HIV, insulin resistance and Haiman CA, Knudsen KE, Sutherland RL, 2009; 20:1807-20. activation in mice. Synapse 2009; Elder G, Macaskill P, Strippoli GF. Vitamin Preston AM, Gurisik E, Bartley C, cardiovascular disease. Current Knudsen ES. Cyclin D1b protein 63:236-46. D compounds for people with chronic Laybutt DR, Biden TJ. Reduced Cardiovascular Risk Reports 2009; expression in breast cancer is Muhlhausler BS, Duffield JA, Ozanne SE, kidney disease not requiring dialysis. endoplasmic reticulum (ER)-to-Golgi 3:59-64. independent of cyclin D1a and Pilgrim C, Turner N, Morrison JL, Nguyen NQ, Biankin AV, Leong RW, Cochrane Database Syst Rev protein trafficking contributes to ER associated with poor disease outcome. McMillen IC. The transition from fetal Chang DK, Cosman PH, Delaney P, 2009:CD008175. stress in lipotoxic mouse beta cells by Samaras K. Prevalence and pathogenesis Oncogene 2009; 28:1812-20. growth restriction to accelerated Kench JG, Merrett ND. Real time promoting protein overload. of diabetes mellitus in HIV-1 infection postnatal growth: a potential role for intraoperative confocal laser Patterson KI, Brummer T, O'Brien PM, Diabetologia 2009; 52:2369-2373. treated with combined antiretroviral Millar EK, Graham PH, O'Toole SA, insulin signalling in skeletal muscle. J microscopy-guided surgery. Ann Surg Daly RJ. Dual-specificity phosphatases: therapy. J Acquir Immune Defic Syndr McNeil CM, Browne L, Morey AL, Physiol 2009; 587:4199-211. 2009; 249:735-7. critical regulators with diverse cellular 2009; 50:499-505. Eggleton S, Beretov J, Theocharous C, targets. Biochem J 2009; 418:475-89. R ...... Capp A, Nasser E, Kearsley JH, Delaney Murphy NC, Biankin AV, Millar EK, Nguyen TV. Calcium supplement and Samaras K, Botelho NK, Chisholm DJ, G, Papadatos G, Fox C, Sutherland RL. McNeil CM, O'Toole SA, Segara D, Crea bone loss. Osteoporos Int 2009; Peters AA, Buchanan G, Ricciardelli C, Rajala A, Daly RJ, Tanito M, Allen DT, Lord RV. Subcutaneous and visceral Prediction of local recurrence, distant P, Olayioye MA, Lee CS, Fox SB, Morey 20:2149. Bianco-Miotto T, Centenera MM, Harris Holt LJ, Lobanova ES, Arshavsky VY, adipose tissue gene expression of serum metastases, and death after breast- AL, Christie M, Musgrove EA, Daly RJ, JM, Jindal S, Segara D, Jia L, Moore NL, Rajala RV. Growth factor receptor- adipokines that predict Type 2 diabetes. conserving therapy in early-stage Lindeman GJ, Henshall SM, Visvader JE, Henshall SM, Birrell SN, Coetzee GA, bound protein 14 undergoes light- Obesity (Silver Spring) Epub invasive breast cancer using a five- Sutherland RL. Loss of STARD10 O Sutherland RL, Butler LM, Tilley WD. dependent intracellular translocation in 2009/12/19...... biomarker panel. J Clin Oncol 2009; expression identifies a group of poor Androgen receptor inhibits estrogen rod photoreceptors: functional role in 27:4701-8. prognosis breast cancers independent of O'Shaughnessy DV, Elder GJ. Review receptor-alpha activity and is prognostic retinal insulin receptor activation. Samaras K, Gan SK, Peake PW, Carr A, HER2/Neu and triple negative status. article: Patient-level outcomes: the in breast cancer. Cancer Res 2009; Biochemistry 2009; 48:5563-72. Campbell LV. Proinflammatory markers, Milner KL, Chisholm D, George J. The Int J Cancer 2009; 126:1445-1453. missing link. Nephrology (Carlton) 69:6131-40. insulin sensitivity, and cardiometabolic many faces of hepatitis C: liver disease 2009; 14:443-51. Ramakrishnan SN, Lau P, Crowther LM, risk factors in treated HIV infection. and Type 2 diabetes. Hepatology 2009; Musgrove EA, Sutherland RL. Biological Pham HV, Dang DT, Tran Minh NN, Cleasby ME, Millard S, Leong GM, Obesity (Silver Spring) 2009; 17:53-9. 50:668-70. determinants of endocrine resistance in O'Toole SA, Swarbrick A, Sutherland RL. Nguyen ND, Nguyen TV. Correlates of Cooney GJ, Muscat GE. Rev-erb beta breast cancer. Nat Rev Cancer 2009; The Hedgehog signalling pathway as a environmental factors and human regulates the Srebp-1c promoter and Samaras K, Wand H, Law M, Emery S, Milner KL, van der Poorten D, Trenell M, 9:631-43. therapeutic target in early breast cancer plague: an ecological study in Vietnam. mRNA expression in skeletal muscle Cooper DA, Carr A. Dietary intake in Jenkins AB, Xu A, Smythe G, Dore GJ, development. Expert Opin Ther Targets Int J Epidemiol 2009; 38:1634-41. cells. Biochem Biophys Res Commun HIV-infected men with lipodystrophy: Zekry A, Weltman M, Fragomeli V, 2009; 13:1095-103. 2009; 388:654-9. relationships with body composition, George J, Chisholm DJ. Chronic hepatitis N Phan TG, Gray EE, Cyster JG. The visceral fat, lipid, glucose and adipokine ...... C is associated with peripheral rather microanatomy of B cell activation. Curr Randall KL, Lambe T, Johnson A, Treanor metabolism. Curr HIV Res 2009; than hepatic insulin resistance. Navaneethan SD, Palmer SC, Craig JC, P Opin Immunol 2009; 21:258-65. B, Kucharska E, Domaschenz H, Whittle 7:454-61...... Gastroenterology Epub 2009/12/08. Elder GJ, Strippoli GF. Benefits and B, Tze LE, Enders A, Crockford TL, harms of phosphate binders in CKD: a Painsipp E, Herzog H, Holzer P. Evidence Phan TG, Green JA, Gray EE, Xu Y, Bouriez-Jones T, Alston D, Cyster JG, Sandhu SK, Nguyen ND, Center JR, Milner KL, van der Poorten D, Xu A, systematic review of randomized from knockout mice that neuropeptide- Cyster JG. Immune complex relay by Lenardo MJ, Mackay F, Deenick EK, Pocock NA, Eisman JA, Nguyen TV. Bugianesi E, Kench JG, Lam KS, controlled trials. Am J Kidney Dis 2009; Y Y2 and Y4 receptor signaling prevents subcapsular sinus macrophages and Tangye SG, Chan TD, Camidge T, Brink Prognosis of fracture: evaluation of Chisholm DJ, George J. 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Abdominal shotgun wound with pellet Mitchell CJ, Nelson AE, Cowley MJ, patients (Protocol). In: COCHRANE DB locomotor and depression-related RL, Biankin AV. Messina: a novel analysis embolization leading to bilateral lower Kaplan W, Stone G, Sutton SK, Lau A, SYST REV. 17/6/09. Ist issue 19/4/06 behaviour in female neuropeptide-Y Y1 tool to identify biologically relevant Rasiah KK, Gardiner-Garden M, Padilla limb amputation: case report and review Lee CM, Ho KK. Detection of growth ed: John Wiley & Sons; 2009. p. Art. receptor knockout mice. J molecules in disease. PLoS ONE 2009; EJ, Moller G, Kench JG, Alles MC, of the literature of missile emboli over hormone doping by gene expression No.: CD006023. Psychopharmacol Epub 2009/04/09. 4:e5337. Eggleton SA, Stricker PD, Adamski J, the past 10 years. J Trauma 2009; profiling of peripheral blood. J Clin Sutherland RL, Henshall SM, Hayes VM. 67:E202-8. Endocrinol Metab 2009; 94:4703-9. Nelson AE, Ho KK. Demographic factors Palmer SC, McGregor DO, Craig JC, Poehls J, Wassel CL, Harris TB, Havel PJ, HSD17B4 overexpression, an influencing the GH system: Implications Elder G, Macaskill P, Strippoli GF. Vitamin Swarbrick MM, Cummings SR, Newman independent biomarker of poor patient Schofield PR, Williams LM, Paul RH, Gatt Mithal A, Wahl DA, Bonjour JP, for the detection of GH doping in sport. D compounds for people with chronic AB, Satterfield S, Kanaya AM. outcome in prostate cancer. Mol Cell JM, Brown K, Luty A, Cooper N, Grieve Burckhardt P, Dawson-Hughes B, Growth Horm IGF Res 2009; 19:327-32. kidney disease requiring dialysis. Association of adiponectin with Endocrinol 2009; 301:89-96. S, Dobson-Stone C, Morris C, Kuan SA, PUBLICATIONS PUBLICATIONS ...... 78 79

Gordon E. Disturbances in selective associated with bone mineral density. Increased novelty-induced motor Turner N, Hariharan K, TidAng J, Ablation of ARNT/HIF1beta in liver Ma CS, Li QJ, Parish CR, Mackay CR, information processing associated with Nat Genet 2009; 41:15-7. activity and reduced depression-like Frangioudakis G, Beale SM, Wright LE, alters gluconeogenesis, lipogenic gene Vinuesa CG. The transcriptional the BDNF Val66Met polymorphism: behavior in neuropeptide Y (NPY)-Y4 Zeng XY, Leslie SJ, Li JY, Kraegen EW, expression, and serum ketones. Cell repressor Bcl-6 directs T follicular evidence from cognition, the P300 and Su LJ, Auluck PK, Outeiro TF, Yeger- receptor knockout mice. Neuroscience Cooney GJ, Ye JM. Enhancement of Metab 2009; 9:428-39. helper cell lineage commitment. fronto-hippocampal systems. Biol Lotem E, Kritzer JA, Tardiff DF, 2009; 158:1717-30. muscle mitochondrial oxidative capacity Immunity 2009; 31:457-68. Psychol 2009; 80:176-88. Strathearn KE, Liu F, Cao S, Hamamichi and alterations in insulin action are lipid Watt MJ, Kraegen EW. Fat partitioning S, Hill KJ, Caldwell KA, Bell GW, Fraenkel Teixeira L, Sousa DM, Nunes AF, Sousa species dependent: potent tissue- and insulin sensitivity: robbing Peter to Yu D, Vinuesa CG. Roquin defects reveal Scott DP, Greenfield JR, Bramah V, E, Cooper AA, Caldwell GA, McCaffery MM, Herzog H, Lamghari M. NPY specific effects of medium-chain fatty pay Paul? Diabetes 2009; 58:16-7. a role for the microRNA machinery in Alford J, Bennett C, Markus R, Campbell JM, Rochet JC, Lindquist S. Compounds revealed as a critical modulator of acids. Diabetes 2009; 58:2547-54. regulating autoimmunity In: Zouali M, LV. Challenges in secondary stroke from an unbiased chemical screen osteoblast function in vitro: New Webster KE, Walters S, Kohler RE, editor. The Epigenetics of Autoimmune prevention: prevalence of multiple reverse both ER-to-Golgi trafficking insights into the role of Y1 and Y2 Mrkvan T, Boyman O, Surh CD, Grey ST, Diseases: John Wiley & Sons 2009. p. metabolic risk factors, including defects and mitochondrial dysfunction receptors. J Cell Biochem 2009; V Sprent J. In vivo expansion of T reg cells 261-278...... abnormal glycaemia, in ischaemic stroke in Parkinson's disease models. Dis Model 107:908-916. with IL-2-mAb complexes: induction of and TIA. Intern Med J Epub Mech Epub 2009/12/30. van Leeuwen EM, Sprent J, Surh CD. resistance to EAE and long-term 2009/04/23. Thomas HE, Biden TJ. Bad news for Generation and maintenance of memory acceptance of islet allografts without Z ...... Sun C, Vallotton P, Wang D, Lopez JA, beta-cell apoptosis. Diabetes 2009; CD4(+) T Cells. Curr Opin Immunol immunosuppression. J Exp Med 2009; Sirard JC, Didierlaurent A, Cayet D, Ng Y, James DE. Membrane boundary 58:1725-7. 2009; 21:167-72. 206:751-60. Zardawi SJ, O'Toole SA, Sutherland RL, Sierro F, Rumbo M. Toll-like receptor 5- extraction using circular multiple paths. Musgrove EA. Dysregulation of and lymphotoxin beta receptor- Pattern Recognition 2009; 42:523-530. Timpson NJ, Tobias JH, Richards JB, Vila de Muga S, Timpson P, Cubells L, Wittmann W, Schunk E, Rosskothen I, Hedgehog, Wnt and Notch signalling dependent epithelial Ccl20 expression Soranzo N, Duncan EL, Sims AM, Evans R, Hayes TE, Rentero C, Gaburro S, Singewald N, Herzog H, pathways in breast cancer. Histol involves the same NF-kappaB binding Sutherland RL, Musgrove EA. CDK Whittaker P, Kumanduri V, Zhai G, Hegemann A, Reverter M, Leschner J, Schwarzer C. Prodynorphin-derived Histopathol 2009; 24:385-98. site but distinct NF-kappaB pathways inhibitors as potential breast cancer Glaser B, Eisman J, Jones G, Nicholson Pol A, Tebar F, Daly RJ, Enrich C, Grewal peptides are critical modulators of and dynamics. Biochim Biophys Acta therapeutics: new evidence for G, Prince R, Seeman E, Spector TD, T. Annexin A6 inhibits Ras signalling in anxiety and regulate neurochemistry Zhao JT, Hill AP, Varghese A, Cooper AA, 2009; 1789:386-94. enhanced efficacy in ER+ disease. Brown MA, Peltonen L, Smith GD, breast cancer cells. Oncogene 2009; and corticosterone. Swan H, Laitinen-Forsblom PJ, Rees MI, Breast Cancer Res 2009; 11:112. Deloukas P, Evans DM. Common 28:363-77. Neuropsychopharmacology 2009; Skinner JR, Campbell TJ, Vandenberg JI. Siyambalapitiya S, Jonsson P, variants in the region around Osterix are 34:775-85. Not All hERG pore domain mutations Koltowska-Haggstrom M, Gaillard R, Ho associated with bone mineral density Vinuesa CG, Rigby RJ, Yu D. Logic and have a severe phenotype: G584S has K, Ross RJ. Cross-sectional analysis of T and growth in childhood. Hum Mol extent of miRNA-mediated control of Wohrle FU, Daly RJ, Brummer T. How to an inactivation gating defect with mild ...... testosterone therapies in hypopituitary Genet 2009; 18:1510-7. autoimmune gene expression. Int Rev Grb2 a Gab. Structure 2009; 17:779-81. phenotype compared to G572S, which men on stable pituitary hormone Tan EY, Yan M, Campo L, Han C, Takano Immunol 2009; 28:112-38. has a dominant negative trafficking replacement. Clin Endocrinol (Oxf) E, Turley H, Candiloro I, Pezzella F, Tindall EA, Petersen DC, Woodbridge P, Wohrle FU, Daly RJ, Brummer T. defect and a severe phenotype. J 2009; 70:907-13. Gatter KC, Millar EK, O'Toole SA, McNeil Schipany K, Hayes VM. Assessing high- Function, regulation and pathological Cardiovasc Electrophysiol 2009; CM, Crea P, Segara D, Sutherland RL, resolution melt curve analysis for W roles of the Gab/DOS docking proteins. 20:923-30...... Sousa DM, Herzog H, Lamghari M. NPY Harris AL, Fox SB. The key hypoxia accurate detection of gene variants in Cell Commun Signal 2009; 7:22. signalling pathway in bone homeostasis: regulated gene CAIX is upregulated in complex DNA fragments. Hum Mutat Walters S, Webster KE, Sutherland A, Zhao L, Lee BY, Brown DA, Molloy MP, Y1 receptor as a potential drug target. basal-like breast tumours and is 2009; 30:876-83. Gardam S, Groom J, Liuwantara D, Marino Wright LE, Cooney G, Turner N. Insulin Marx GM, Pavlakis N, Boyer MJ, Curr Drug Targets 2009; 10:9-19. associated with resistance to E, Thaxton J, Weinberg A, Mackay F, resistance and mitochondrial Stockler MR, Kaplan W, Breit SN, chemotherapy. Br J Cancer 2009; Toussaint ND, Elder GJ, Kerr PG. Brink R, Sprent J, Grey ST. Increased dysfunction in muscle: is there a link? . Sutherland RL, Henshall SM, Horvath Sprent J, Surh CD. Re-entry of mature T 100:405-11. Bisphosphonates in chronic kidney CD4+Foxp3+ T cells in BAFF-transgenic Asia-Pacific Journal of Endocrinology LG. Identification of candidate cells to the thymus: an epiphenomenon? disease; balancing potential benefits and mice suppress T cell effector responses. 2009; 1:55-64. biomarkers of therapeutic response to Immunol Cell Biol 2009; 87:46-9. Tangye SG, Cook MC, Fulcher DA. adverse effects on bone and soft tissue. J Immunol 2009; 182:793-801. docetaxel by proteomic profiling. Cancer Insights into the role of STAT3 in human Clin J Am Soc Nephrol 2009; 4:221-33. Res 2009; 69:7696-703. Stockli J, James DE. Insulin action under lymphocyte differentiation as revealed Y Wang L, Madigan MC, Chen H, Liu F, ...... arrestin. Cell Metab 2009; 9:213-4. by the hyper-IgE syndrome. J Immunol Tran BN, Nguyen ND, Center JR, Eisman Patterson KI, Beretov J, O'Brien PM, Li Y. Zhao P, Yang L, Lopez JA, Fan J, Burchfield 2009; 182:21-8. JA, Nguyen TV. Enhancement of Absolute Expression of urokinase plasminogen Yu D, Batten M, Mackay CR, King C. JG, Bai L, Hong W, Xu T, James DE. 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MicroRNAs in common Wang XL, Suzuki R, Lee K, Tran T, Yu D, Rao S, Tsai LM, Lee SK, He Y, JR, Eisman JA, Christiansen C, diseases and potential therapeutic Gunton JE, Saha AK, Patti ME, Goldfine Sutcliffe EL, Srivastava M, Linterman M, Sigurdsson G, Kong A, Thorsteinsdottir Tasan RO, Lin S, Hetzenauer A, applications. Clin Exp Pharmacol Physiol A, Ruderman NB, Gonzalez FJ, Kahn CR. Zheng L, Simpson N, Ellyard JI, Parish IA, U, Stefansson K. New sequence variants Singewald N, Herzog H, Sperk G. 2009; 37:102-107. Financial Highlights ...... 81

Garvan Institute of Medical Research 2005 2006 2007 2008 2009 Income Statement $'000 $'000 $'000 $'000 $'000

NHMRC Grants 12,080 13,832 16,682 18,695 19,094 Other Peer Reviewed Grants 6,865 8,184 8,530 9,159 11,061 Other Grants 200 655 1,068 4,811 16,524 NSW Government Grant 3,720 12,174 4,063 4,026 3,797 Commonwealth Government Grant - 4,700 1,193 - - Commercial Collaborations 2,043 4,091 2,714 1,289 737 Garvan Research Foundation 2,343 2,562 3,817 4,689 5,290 Other Income 2,774 2,916 3,543 4,050 7,470 Total Operating Income 30,025 49,114 41,610 46,719 63,973

Remuneration Costs 17,377 21,983 23,621 27,337 28,322 Research Expenditure* 4,571 5,879 7,640 9,377 7,883 Administration and Information Technology 2,931 3,913 3,771 5,331 4,822 Building and Scientific Operations 2,378 2,438 2,461 2,753 3,324 Total Operating Expenses 27,257 34,213 37,493 44,798 44,351

Building Asset Amortisation (1,171) (1,171) (1,180) (1,189) (1,657) Property, Plant and Equipment Depreciation (2,178) (2,449) (2,433) (2,390) (2,597) Transfer from/(to) Building Reserve 1,047 (1,353) 1,047 1,047 1,047 Endowment Grants 745 10,965 2,210 3,953 6,388 Endowment Earnings 1,011 2,181 2,589 1,700 958 Donations & Bequests direct to/(from) Endowment Fund - - - 5,393 (5,000) Unrealised gain/(loss) on Endowment Fund Investments - - - (7,407) 1,922

Net Income 2,222 23,074 6,350 3,028 20,683 Accumulated Surplus Brought Forward 922 308 9,914 11,109 16,571 Transfer from/(to) Research Program Reserve (1,110) (107) (2,526) 380 (2,189) Transfer from/(to) Endowment Reserve (1,726) (11,809) (3,664) 1,847 (2,530) Transfer from/(to) Infrastructure Expense Reserve - (1,552) 1,035 207 (23) Accumulated Surplus Carried Forward 308 9,914 11,109 16,571 32,512

*The figures in 2006 and 2007 have been adjusted to improve the comparability with 2008. FINANCIAL HIGHLIGHTS FINANCIAL HIGHLIGHTS ...... 82 83

Garvan Instititute of Medical Research Garvan Research Foundation 2005 2006 2007 2008 2009 2005 2006 2007 2008 2009 Balance Sheet $'000 $'000 $'000 $'000 $’000 Statement of Funds $'000 $'000 $'000 $'000 $’000

Current Assets 5,632 15,249 18,226 21,114 52,136 Donations & Pledges 2,524 3,826 4,961 6,861 5,562 Property, Plant and Equipment 40,022 40,903 45,160 60,085 62,056 Events 266 332 409 105 244 Endowment Fund* 11,630 23,439 27,103 25,255 27,786 Bequests 928 10,315 1,847 3,132 7,764 Investment in Associates - 84 84 84 84 Interest and Other Income 42 21 25 55 19 Total Assets 57,284 79,675 90,573 106,538 142,062 Total Income 3,760 14,494 7,242 10,153 13,589

Current Liabilities** 3,547 6,900 8,343 7,860 23,372 Fundraising Expenses (607) (1,018) (1,184) (1,114) (1,268) Provisions 2,457 3,069 3,042 3,545 3,986 Borrowings 6,000 - 4,179 18,144 18,078 Public Awareness Program (66) - - - - Total Liabilities 12,004 9,969 15,564 29,549 45,436 Grants to GSVCC Joint Venture Partner - - - - (1,170) Net Funds Raised 3,087 13,476 6,058 9,039 11,151 Accumulated Surplus 308 9,914 11,109 16,571 32,512 Reserves 44,972 59,792 63,900 60,419 64,114 Accumulated Funds Prior Years 130 129 78 109 507 Total Net Funds 45,280 69,706 75,009 76,990 96,626 Funds Available for Grants to Institute: 3,217 13,605 6,136 9,148 11,658 * Including cash and investments at market value. ** The figures in 2006 and 2007 have been adjusted to improve the comparability with 2008. General Research 850 871 750 926 1,010 Specific Research 1,493 1,691 3,067 3,762 4,280 Endowment Funds 745 10,965 2,210 3,953 6,388 Total Grants 3,088 13,527 6,027 8,641 11,678

Accumulated Funds Carried Forward 129 78 109 507 (20) Represented By: Assets 182 251 311 1,391 164 Liabilities (53) (173) (202) (884) (184) Net Assets 129 78 109 507 (20) Garvan Institute of Medical Research 384 Victoria Street Darlinghurst Sydney NSW 2010 Australia T +61 2 9295 8100 F +61 2 9295 8101 www.garvan.org.au

Project Manager Alison Heather Design Jason McDonald Photography Penelope Clay

Published April 2010 Copies of the Annual Report can be obtained by contacting: Gabriella O’Neil [email protected] T +61 2 9295 8120