Annual Report 2009 ANZAC Research Institute

ANZAC Research Institute

ANZAC Research Institute ANZACHospital ResearchRoad, Concord Institute Hospital Hospital SydneyRoad, ConcordNSW 2139 Hospital Sydney NSW 2139 Telephone: (02) 9767 9100 or Facsimile: (02) 9767 9101 Telephone:www.anzac.edu.au (02) 9767 9100 Email: or Facsimile: [email protected] (02) 9767 9101 www.anzac.edu.au Email: [email protected] ANZAC Health & Medical Research Foundation ABN 48 066 780 005 ANZAC ANZAC Health & Medical Research Foundation ABN 48 066 780 005 Biennial Report 2013-15 Research Institute

ANZAC Research Institute GIVING OPPORTUNITIES

ABOUT US □ Yes. I would like to help ANZAC Health & Medical Research Foundation.

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To provide Leadership and excellence in health and medical research activities throughout Australia, □ Please send me more information about the Foundation’s Bequest Program, including the recognition of benefactors. with a focus on aging, to improve the future health and medical care for the Australasian community. In so doing, the Foundation will provide a lasting legacy to the veterans and their families who have □ A gift to continue vital scientific research. created the society we have today. □ Please send me more information on the FOTARI.

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• To encourage, collaborate in and undertake basic, clinical and epidemiological research, with a ______particular focus on ageing, that aims to improve health and medical care and is dedicated to the memory of our war veterans and their families. Postcode:______

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For further information contact: ANZAC Health & Medical Research Foundation ANZAC Research Institute Hospital Road CONCORD NSW 2139 Telephone: (02) 9767 9100 or Facsimile: (02) 9767 9101 www.anzac.edu.au Email: [email protected] All gifts over $2.00 are tax deductible

Cover image: Courtesy Lynley Pilon. Contents

Chairman’s Report ...... 2 Chairman’s Report ...... 3 Director’s Report 2013-2015 ...... 4

ANZAC Research Institute Research Groups

Adrenal Steroid ...... 6 Andrology ...... 6 Atherosclerosis ...... 7 Biogerontology ...... 7 Bone Biology ...... 8 Burns Research and Reconstructive Surgery ...... 8 Dendritic Cell Research ...... 8 Geriatric Epidemiology ...... 9 Northcott Neuroscience Laboratory ...... 9 Vascular Biology and Platelet and Thrombosis Research Lab ...... 10

Our Research and Staff

Ongoing Studies ...... 11 Highlights & Prizes ...... 19 Collaborations: Summary ...... 22 Staff & Students 2013-2013 ...... 25 Grants & Contracts 2013-2015 ...... 28 Publications ...... 31 Financial Performance ...... 38 Board ...... 39 Donor Honor Roll ...... 44

Annual Financial Report & Independent Audit Reports

Annual Financial Reports available at http://www .anzac .edu .au

Biennial Report 2013-15 1 Chairman’s Report

I am pleased to present the biennial report from the board of the ANZAC Research Institute .

During the past two years the Institute has continued to progress very well, ever onward and upward . Over that time there have been some changes in the board membership, some due Directors reaching their full term and others due to retirement from SLHD positions for which they were nominees . These include Mrs Eve Bosak, Prof Bruce Robinson, his alternates Profs Ben Freedman & Arthur Conigrave as well as Matthew Swanborough, Dr Ross Bradbury and Emeritus Prof Michael Field . Prof Field will continue his valued services as one of the Institute’s external advisers in scientific integrity . Balancing this and with changes of the governance status of the ANZAC, we welcome newcomers George Elias, Dr Tim Sinclair, Dr Ilona Cunnigham, Dr Meng Ngu, Dr Katherine Moore and Prof Andrew McLachlan .

To ensure the smooth running of the ANZAC Research Institute’s finances and we have also secured the services of Peter Tan, who has decades of accounting expertise and experience in the financial management of the SLHD and its predecessors, to assist the Institute’s Finance Manager, Annet Doss .

The board has been in the habit of commencing each meeting with a presentation from one of its senior researchers . This practice has filled us with some awe and considerable pride as we gain fresh purpose in the Board’s efforts to support the Institute’s work .

The MRIs affiliated with the University of Sydney have continued extended negotiations on the details of their affiliation agreements, exploring the nature of the relationships as well as the financial arrangements . It is with considerable pleasure I can report the successful outcome of these negotiations as signified by the subsequent signing of a multi-year agreement between the Institute and the University of Sydney .

In keeping with MRIs around the country, we applauded the establishment of the Medical Research Fund by the Federal Govt and keenly look forward to the time when this major boost to medical research funding flows to the coal face .

During this centenary of the ANZAC landings, I was able to make my own private journey to the Gallipoli Peninsula in April . This allowed me to look with awe upon the extraordinary terrain which faced these young soldiers . The legend is less powerful than the real history of these events told by dispatches, the incredible letters and diary notes that eventually found their way back to Australia .

Finally, I wish to advise of my own retirement from the board . Fortunately my able deputy chair, Prof Bob Lusby AM, was prevailed upon by the rest of the board to accept the Chairman’s role - another smooth transition . Bob has the distinction of being an academic surgeon on the staff of CRGH, as well as an active member of the military who has served in peacekeeping forces in both Rwanda & East Timor .

I would like to thank all members of the board, particularly our scientific director Prof David Handelsman, and Dr Teresa Anderson CEO of SLHD, whose support & intervention have made all the difference to ARI .

I leave you in good hands,

Diana Horvath

2 Biennial Report 2013-15 Chairman’s Report

It is a great privilege to follow Dr . Diana Horvath as Chair of the ANZAC Health and Medical Research Foundation and gratefully acknowledge her leadership and steady hands in guiding us over the past years . It seems hard to believe the Foundation has been going for over 20 years, I can remember our first fund raising dinner in a marquee set in the grounds of Victoria Barracks . A lot of people have helped us over the years with initial funding of Six million dollars coming from the Commonwealth and State governments to mark in real terms the ending of the Second World War .

It was very fitting that the Institute be sited in the grounds of Concord Hospital, the successor of the 113 Australian General Hospital . Built to care for the casualties of the Second World War, there was a need to reassure our service men and women that there would be a first class Hospital to care for them if needs be .

The Department of Veterans Affairs subsequently took over the Hospital, then known as the Repatriation General Hospital . The DVA with great insight realized that to maintain high standards in a post war setting, it would benefit from inviting the University of Sydney to open a Clinical School . One essential arm of a Teaching Hospital is Research, which attracts high quality staff that benefits both patients and students and enables clinically important questions to be addressed . So out of that need the ANZAC Health and Medical Research Foundation was formed from which the ANZAC Research Institute arises . The Foundation is affiliated with the University of Sydney and is a controlled entity of Sydney Local Health District, being in the grounds of Concord Hospital .

The Institute has been very focused on first class research most capably led by Professor David Handelsman . The majority of our day to day funding comes from grants competitively awarded (some $11 million a year), which reflects the quality of the work done . The Foundation has grown to having over $31million in assets and some 150 people engaged in research and its support including 60 post graduate (mostly PhD) students and in 2014-15 some 249 publications came out of the institute .

The important work from 10 research areas including ageing, cardiovascular disease, bone metabolism, genetics, dendritic cell, reproduction and andrology has gained significant recognition in recent years reflecting the efforts of this small but effective institute .

As the ANZAC Research Institute grows I hope to bring more attention to its outstanding work and allow it to demonstrate the outcomes of its work and the trust placed in it carrying the iconic name of ANZAC .

Robert Lusby AM

2015 Incoming Chair

Biennial Report 2013-15 3 Director’s Report 2013-2015

Welcome to the ANZAC Research Institute’s Biennial Report .

Now in the middle of our second decade, the ANZAC Research Institute is thriving as an independent medical research institute supporting its co-located teaching hospital and affiliated medical school . As the Concord Hospital campus’s own medical research institute, in addition to our earned reputation for scientific excellence, the Institute is achieving its goal of maintaining a researcher-friendly environment for biomedical scientists to achieve the best they can in making important progress over a wide variety of areas as outlined further in this Report .

Starting from scratch in 2000, the ANZAC now provides a scientific home for 150 scientific staff including 50 graduate (mostly PhD) students working in research groups over a wide range of disciplines in modern biomedical science . Together they earn over $10 million of external research funding and produce over 120 peer-reviewed research papers per year . From the opening of our main building in 2000, the research lab facilities have expanded to include additional research labs (ANZAC2) on the upper floor of the adjacent Bernie Banton Centre building, which we share with the Asbestos Diseases Research Institute housed on the ground floor, and the ANZAC3 research labs located in the Hospital main building .

The dynamic of medical research is that its major progress is based on new ideas or new technologies . For new ideas, we rely on attracting the best and brightest scientists . But they require the best new technologies to identify, visualize or quantify new molecules and biological mechanisms at the research frontier . Through this process we discover the biological weaknesses which create disease and disability and this new knowledge reveals opportunities to develop new biomarkers, diagnostic tests and therapeutic targets that can improve medical management of disease . In tackling the major challenge to equip our scientists with the state-of-the- art tools necessary to make their innovative contributions, the Institute has recently undergone major upgrades to our major equipment and facilities . This includes acquiring top-line equipment such as a white light laser confocal microscope (Leica SP8) capable of monitoring 8 different emissions simultaneously, and a multichannel flow cytometer (BD LSR Fortessa™ X-20) featuring five lasers and 18 colors . Another major development is SLHD’s construction underway of the Translational Research Facility (TRF) . This new animal facility will house a wide range of high-end, non-invasive imaging and metabolic monitoring facilities for small animals and the ability to undertake experimental bone marrow transplantation . Together, these state-of-the-art facilities guarantee that ANZAC scientists will have the tools necessary to stay at the forefront of discovery science and innovation .

The last few years have been very difficult times for funding of medical research . While we have the Medical Research Future Fund (MRFF) to look forward to on the distant horizon, in the last few years the success rates for NHMRC grant applications has dropped by close to 50% . There is no sign this will improve in the next few years before the MRFF starts to restore these drastic shortfalls . In the meantime, our career medical researchers as well as the upcoming generation now find their career paths disappearing with the impeding loss of decades of scientific training and expertise . While we get the government we deserve, the dire situation for career medical researchers in this country is not widely understood . Similarly, our Institute’s main support for its operating costs comes from the NSW government together with a contribution from the Commonwealth government via research income generated by our Institute scientists for the University . More direct community support in the form of gifts, donations and bequests is also received with gratitude .

4 Biennial Report 2013-15 There are many people to thank for the Institute’s ongoing success . Thanks are especially due to the Institute’s excellent management team of Julie Taranto, Annet Doss, Candice Chang, Tracey Dent, Mark Jimenez, Mamdouh Khalil, Justin Crosbie and Rachelle Innes who ensure it operates smoothly, efficiently and with deft personal touch . We also owe thanks to our major stakeholder, Concord Hospital and the Sydney Local Health District . In particular Tim Sinclair, Concord Hospital’s General Manager, and Teresa Anderson, the SLHD’s Chief Executive, provide unwavering goodwill and support which is crucial for the Institute’s operations . Similarly, the ongoing support of the Sydney Medical School, especially the Dean Professor Bruce Robinson and Professor Arthur Conigrave is gratefully acknowledged . Thanks are also due to John Gatfield for editing our newsletter Discovery . Finally, my personal thanks go to Professor Diana Horvath and her successor Professor Bob Lusby as Board Chairs, together with the Board for its unflagging support and enlightened commitment which set the stage for making the Institute as good as it can be . Above all, it remains the pinnacle of privilege in a fortunate life to work in the challenging and productive environment created by the Institute’s scientists whose inspiring commitment make all efforts on their behalf worthwhile .

Admin Staff

MPU Staff

Biennial Report 2013-15 5 ARI Research Groups

Adrenal Steroid

Group Leader: Professor Mark Cooper Senior Scientist: Dr Jinwen Tu

The Adrenal Steroid group was established in 2013 and focusses on the role of endogenous glucocorticoids in a range of common medical illnesses . The group has strong clinical/ translational research ties with the Universities of Birmingham and Leeds in the UK . The role of adrenal steroids in osteoporosis and arthritis are being explored in collaboration with the Bone Biology Group . The role of local cortisol production in burn injury is being explored in collaboration with the Burn Research Group . Australian based research is supported by an NHMRC Project Grant and the Rebecca Cooper Foundation .

Andrology

Group Leader: Professor David Handelsman Senior Scientist: Dr Charles Allan, Ms Reena Desai, Dr Ulla Simanainen, Dr Kirsty Walters, Dr Pekka Keski- Rahkonen .

The Andrology group purses basic, applied and clinical research in male reproductive health, medicine and biology .

Andrology is literally the study of man (Greek andros, man) . The medical and scientific discipline is defined as the study of male reproductive health, medicine and biology . Male Reproductive Health involves the overlapping domains of Fertility, Sexuality and Androgenisation which overlap with male general health especially with regard to androgen effects .

The Andrology group focuses on both the biological and clinical effects of androgens on male health, in particular men’s reproductive and general health across all ages . Androgens (male hormones), the main one being testosterone, occur naturally in the body and play far-reaching roles in many body systems, particularly in male reproduction, fertility and sexuality . They exert important influence on most non-reproductive tissues especially the prostate, cardiovascular system, bone and the brain, throughout the entire male lifespan and may also influence women’s health .

The Andrology group is a collaboration of the:

• Andrology Laboratory at the ANZAC Research Institute where the focus is on the physiology and pharmacology of androgens in males and females, by undertaking research using experimental animal models and laboratory bench research • Andrology Department of Concord Hospital, where patient and community centred research is carried out

6 Biennial Report 2013-15 and translated into improvements in patient care . The focus is on the therapeutic use of androgens such as to treat hormone deficiency states in adolescence and adulthood, in certain chronic diseases, for male contraception and for ageing men . In addition we also study the relatively widespread misuse/overuse and abuse of androgens for many wishful or harmful non-medical reasons as well as in sports doping . Atherosclerosis

Group Leaders: Professor Len Kritharides and Professor Wendy Jessup Senior scientists: Dr Maaike Kockx

Atherosclerosis is a hardening and narrowing of the arteries due to the formation of atherosclerotic plaques within the vessel wall . These plaques encroach on the arterial lumen, interfering with blood flow and in acute events can rupture, blocking blood flow completely . Atherosclerosis is the underlying disease leading to a wide variety of cardiovascular related illnesses and can lead to clinical outcomes such as heart attacks or strokes when rupture occurs .

Macrophages are inflammatory cells that play an important role in the initiation and the progression of the atherosclerotic plaque . Within a lesion, macrophages take up large amounts of cholesterol rendering them macrophage foam cells . These foams cells can be highly inflammatory and exacerbate lesion formation .

In the atherosclerosis laboratory we study aspects of macrophage biology that are important in atherosclerotic plaque formation using in vitro and in vivo models . Our two main areas of interest are:

• Regulation of macrophage protein secretion • Mechanisms involved in lipid uptake and removal from macrophages and the artery wall Biogerontology

Group Leader: Professor David Le Couteur Senior Scientist: A/Prof Victoria Cogger

The Biogerontology Laboratory in the ANZAC Research Institute is the laboratory component of the Ageing and Alzheimers Institute (AAAI) and Centre for Education and Research on Ageing (CERA) at Concord Hospital . The Biogerontology Laboratory performs research into the biology of ageing and age-related diseases with a major focus on the effects of old age on the liver and the cells of the hepatic sinusoid .

Our objective is to develop strategies to delay and prevent diseases of old age .

Biennial Report 2013-15 7 Bone Biology

Group Leader: Professor Markus J Seibel Senior scientist: A/Prof Hong Zhou

The Bone Research Program pursues basic, applied and clinical research in bone health and biology, including osteoporosis and metabolic bone disease . Our basic research covers three main areas: steroid hormone action in bone, arthritis and cancer bone metastasis . Our applied and clinical research focuses on the assessment of bone metabolism, the implementation of secondary fracture prevention programs, and male ageing . Our research has been continuously supported by competitive grants from the NH&MRC, Cancer Council NSW and many other agencies .

Burns Research and Reconstructive Surgery

Group Leader: Professor Peter Maitz Senior Scientist: Dr Zhe Li and Dr Yiwei Wang

Lack of skin donor site, wound infection and scar formation remain the major issues in treating severe burns .

Our laboratory is committed to develop engineered living skin substitutes as alternative grafts for deep burn wound care . The research involves in generating various biological scaffolds using bio-degradable matrix proteins and synthetic polymers that are biologically compatible, safe and suitable for skin cells to attach and grow . The bio-scaffold could facilitate the repair and regeneration of the damaged dermal tissue and the engineering of living skin substitutes with skin structures comparable to normal human skin . Our research also covers other important aspects in sever burn and reconstructive surgery including burn epidemiology and prevention; wound healing; wound infection; dermal angiogenesis; stem cells for skin regeneration; scarring and wound contraction, nutrition and burn wound healing .

Dendritic Cell Research

Group Leader: Professor Derek Hart Honorary Professorial Research Fellow: Professor Ken Bradstock Senior Scientists: A/Prof Georgina Clark, Dr Phillip Fromm, Dr Pablo Silveira, Dr Xinsheng Ju

Dendritic Cell Research is directed by Professor Derek Hart . They discover key immune markers and biological processes which will provide new diagnostic and therapeutic products for improving patient care .

The immune system controls and regulates our internal and external environmental reactions . It responds by up-regulating or activating cellular and soluble components to fight infection and cancer . Dendritic cells (DC) are unique white blood cells that exist as different subsets throughout the body . They are responsible for initiating and directing immune responses . As one of the pioneering groups in this field, the DCBTG is continuing to define human DC subsets and elaborate their function . The group studies DC surface molecules to determine how these molecules influence DC function and how antibodies targeting them might be used in clinical practice .

8 Biennial Report 2013-15 A major part of our work is aimed at using the patient’s immune responses to treat haematological cancers . We are testing our findings in preclinical models of stem cell transplantation, leukaemia, multiple myeloma, prostate cancer and other malignancies . We are striving to develop novel immunosuppressive strategies, including our previous anti-CD83 antibody as a novel therapeutic agent . We aim to use this antibody to improve transplant outcomes, whilst preserving the patient’s ability to fight infections and cancer . Negotiations to support a clinical trial of anti-CD83 in allogeneic haematopoietic stem cell transplantation are underway .

Geriatric Epidemiology

Group Leader: Professor Robert Cumming Co-investigators: Professor David Handelsman, Professor Markus Seibel, Dr Vasi Naganathan (CERA), Dr Fiona Blyth, Dr Louise Waite (CERA), Professor David Le Couteur (CERA), Professor Stephen Simpson (Charles Perkins Centre), Professor Hal Kendig (ANU), Professor Clive Wright (CERA), Dr Vasant Hirani (CERA)

Epidemiology is the study of the frequency and causes of disease in groups of people (Greek demos, the people) . The Geriatric Epidemiology group is responsible for the Concord Health and Ageing in Men Project (CHAMP), an epidemiological study of health and disease in older men . CHAMP provides a platform to study a wide range of health-related issues in older men . The investigators have skills in epidemiology, andrology, bone biology, dementia, geriatric medicine, rheumatology, biogerontology, nutrition and social science . CHAMP is a real bench to bedside to population study . The data is currently being used to study topics as diverse as the role of testosterone in the aetiology of dementia and identification of factors associated with social participation .

Despite the fact that men who reach the age of 70 still have much lower life expectancy than women of that age, very little research has been done on the health of older men . CHAMP was designed to fill this gap and is one of the world’s most comprehensive studies of the health of older men . Investigation of the role of reproductive hormones, including testosterone, in ageing in men is an important part of CHAMP .

Northcott Neuroscience Laboratory

Group Leader: Professor Garth Nicholson Principal Scientist: A/Professor Marina Kennerson

The Northcott Neuroscience Laboratory, headed by Professor Garth Nicholson is internationally renowned in the field of molecular genetics of human hereditary neuropathies and motor neurone disorders . The laboratory has made important contributions to the discovery of gene mutations causing neurodegeneration of peripheral nerve and motor neurons . The discovery of mutant genes in our families has uncovered new mechanisms causing disease . We are setting up ways to screen compounds for possible treatments . In hereditary sensory neuropathy we have commenced a pilot treatment trial .

Our laboratory is truly translational, and focuses on determining the underlying causes of neurodegenerative disease firstly to develop diagnostic tools and eventually to develop effective therapies .

Biennial Report 2013-15 9 Vascular Biology and Platelet and Thrombosis Research Lab

Group Leaders: Prof Len Kritharides (VBG) and Dr Vivien Chen (PTRL) Senior Clinical Scientists: Prof Ben Freedman, Prof David Brieger, A/Prof Harry Lowe, Dr Andy Yong, Dr Jenny Curnow Senior Scientists: Dr Gabrielle Pennings, Dr Caroline Reddel, Dr Elias Glaros

Cardiovascular disease is considered to be the leading cause of death world-wide and in Australia (30 % of deaths) . Cardiovascular disease includes coronary artery disease (CAD), heart failure, arteriosclerosis, and hypertension . The leading cause of death in Australia in 2013 was ischemic heart disease which results from insufficient blood supply to the heart generally due to blocked arteries around the heart (coronary arteries); this can cause angina (chest pain), heart attack, and death .

Research within the Vascular Biology Group incorporates a mixture of basic and clinical science aimed at understanding, preventing and treating CAD and its complications . Areas of interest include:

• Thrombosis and inflammation in cardiovascular disease • Novel measures of coagulation

At the beginning of 2015, we were pleased to welcome Dr Vivien Chen and her group, the Platelet and Thrombosis Research Lab . There are multiple potential synergies between the VBG and the PTR labs and collaborations have already been established in multiple projects .

Thrombosis is the most common cause of death in the Western world as a result of stroke, myocardial infarction and venous thromboembolism . Our group is interested in the mechanisms of clot formation, the biology of platelets and coagulation proteins and how manipulation of these can be used to influence disease . We use real time intravital fluorescent microscopy and flow cytometry assays to investigate the processes of platelet accumulation and coagulation initiation in the mouse circulation . We use this insight to design translational projects with impact on clinical thrombotic disease . Our particular focuses are: novel assays of coagulation and platelet function and a highly activated “procoagulant” platelets and the role that they play in health and disease .

10 Biennial Report 2013-15 Our Research & Staff

On-going Studies

Following is a summary of the Institute’s current research projects . More detailed information is available upon request

Adrenal Steroid

Role of cortisol metabolism in the CNS in the HPA axis response to inflammation. J Tu, J Sattler, F Buttgereit (Berlin, Germany) Endogenous Glucocorticoids in Immune Arthritis J Tu, S Stoner, MS Cooper, P Stewart (Leeds UK), F Buttgereit (Berlin, Germany), MJ Seibel, H Zhou Endogenous Glucocorticoids in the Development and Progression of Rheumatoid Arthritis R Hardy (Birmingham UK), K Raza (Birmingham UK), MS Cooper Endogenous Glucocorticoids and Ageing H Henneicke, MS Cooper, P Stewart (Leeds UK), MJ Seibel, H Zhou Local Glucocorticoid Production in Skin and its Role in Scar Healing Y Wang, J Tu, P Maitz, MS Cooper

Andrology

PHYSIOLOGY & PHARMACOLOGY OF ANDROGENS Clinical Pharmacology of Testosterone AJ Conway, C Fennell, S Spasovska, L Turner, DJ Handelsman Subcutaneous route of administration of androgen ester injections L Turner, C Fennell, S Spasevska, G Singh, DJ Handelsman Randomised controlled trial of testosterone vs placebo to prevent diabetes (T4DM study) R Iyer, AJ Conway, V Jayadev Pharmacokinetics of testosterone via scrotal transdermal route R Iyer, G Fraser, L Turner Randomised controlled trial of testosterone vs placebo with choice extension phase for androgen deficiency symptoms (T4DM study) G Fraser, R Iyer , L Turner, AJ Conway, V Jayadev , DJ Handelsman

Biennial Report 2013-15 11 Randomised controlled trial of DHT pre-treatment for poor ovarian response in IVF K Walters, N Narayana-Shankara, A Marren, M Bowman, DJ Handelsman

LABORATORY RESEARCH Steroid Mass Spectrometry: measuring steroids in serum and biological samples R Desai, T Harwood, P Keski-Rahkonen, M Jimenez, K Walters, N Narayana-Shankara, DJ Handelsman Development of urine steroid and LH assays for field studies of puberty (Archer study) G Singh, R Desai, T Sivananthan, F Bathur, DJ Handelsman

EXPERIMENTAL STUDIES OF ANDROGEN ACTION Androgens and the Prostate U Simanainen, F Suarez, K McNamara, M Jähne, B Zhao, DJ Handelsman Hormonal regulation of Sertoli cell function and spermatogenesis R Hazra, D Upton, T Rastegar, L Corcoran, J Spaliviero, M Jimenez, DJ Handelsman, CM Allan Androgens, Ageing and Female Reproductive Physiology K Walters, A Caldwell, D Upton, DH Lin, S Lamb, L Middleton, C Cerna, CM Allan, DJ Handelsman Role of Androgens in the Breast and Uterus U Simanainen, K Walters, E Gao, P Choi, B Psarommatis, DJ Handelsman

PUBIC HEALTH ANDROLOGY Hormonal Epidemiology of Male Ageing: The Concord Health in Ageing Men Project (CHAMP) B Hsu, R Cumming, D Le Couteur, MJ Seibel, F Blyth, V Naganathan, DJ Handelsman and others Pharmacoepidemiology of testosterone prescribing and overuse LP Ly, DJ Handelsman Androgen Abuse: Testosterone & Sports Doping A Idan, C Fennell, M Jimenez, DJ Handelsman in collaboration with A Death, L McRobb, K McGrath (Heart Research Institute) and C Goebel, R Kazlausakas, G Trout, C Howe (National Measurement Institute) Statistical methods to deduce population-based profile of androgen status in men and women over a life span K Sikaris, LP Ly, DJ Handelsman Pooled Australian data on androgen status of men B Yeap,G Wittert, LP Ly, DJ Handelsman

12 Biennial Report 2013-15 Atherosclerosis

Macrophage-mediated cleavage of apolipoprotein A-I D Marcal, M Kockx, M Traini, W Jessup, L Kritharides Serum cholesterol efflux capacity D Marcal, M Anastasius, W Jessup, L Kritharides Cyclosporin A-mediated dyslipidemia M Kockx, D Nawara, W Jessup, L Kritharides Biology of SMPDL3A, a macrophage- secreted phosphodiesterase M Traini, R Kumaran, W Jessup, L Kritharides Glycosylation of mouse apolipoprotein E M Traini, M Kockx, D Nawara, W Jessup, L Kritharides HDL functionality in patients with coronary artery disease M Anastasius, M Kockx, W Jessup, L Kritharides Regulation of macrophage apolipoprotein E secretion M Kockx, D Nawara, M Traini, W Jessup, L Kritharides Developing an in silico model of myocardial bridging to examine the association between blood flow perturbations and atherosclerotic plaque progression in patients with myocardial bridging. A Javadzadegan, A Yong, and L Kritharides

Biogerontology

The Biogerontology group carries out research on the biology of ageing . Key focus areas include the liver microcirculation, nutrition and pharmacology .

Ultrastructure of the liver microcirculation Cogger and Le Couteur Nutrition, Ageing and Health Le Couteur, Cogger, Solon-Biet and Simpson Disposal of nanomaterials by livers at the cellular level Cogger, Le Couteur, Roberts and Xu Ageing and late life health: calories, macronutrients or branched chain amino acids? Le Couteur, Simpson, Cogger, Solon-Biet and Buckland

Biennial Report 2013-15 13 Bone Biology

The Role of Glucocorticoids in Bone Metabolism

Effects of Exogenous Glucocorticoids on Bone, Fat and Energy Metabolism S Gasparini, H Henneicke, C Gundberg, H Zhou, MJ Seibel Endogenous Glucocorticoids and Ageing H Henneicke, M Cooper, P Stewart, MJ Seibel, H Zhou Endogenous Glucocorticoids and Diet-induced Bone, Fat and Metabolic Dysregulation S Kim, H Henneicke, S Gasparini, MJ Seibel, H Zhou Endogenous Glucocorticoids in Immune Arthritis J Tu, S Stoner, M Cooper, P Stewart, F Buttgereit, MJ Seibel, H Zhou Preventing the Spread of Malignant Tumours to Bone Y Zheng, C Fong-Yee, C Dunstan, H Zhou, MJ Seibel The role of the Vitain D receptor in malignant bone disease Y Zheng, K Horas, C Fong-Yee, H Zhou, MJ Seibel The Concord Fracture Liaison Service: A world-class research and clinical program for secondary fracture prevention K Ganda, A Lih and MJ Seibel Atypical Femoral Fractures and Bisphosphonate Use C Girgis and MJ Seibel The Concord Health in Ageing Men Project (CHAMP) with Robert Cumming, David Handelsman and others .

Burns Research & Reconstructive Surgery

Skin Tissue Engineering Using a Biodegradable Polymer Y Wang, C Chong, P Maitz and Z Li Efficacy and Safety of Engineered Skin Substitute and Dressing Materials on Skin Wound Healing: A Mouse Model Study Y Wang, C Chong, P Maitz and Z Li Nutritional support on skin formation and wound healing: J Hew, Y Wang, Z Li and P Maitz Biofilm and Infection of Burn Wound P Kennedy, S Brammah and E Wills

14 Biennial Report 2013-15 The effect of endotracheal tube size on voice, swallowing and laryngotracheal injury in patients intubated for thermal burns: a three year observational study N Clayton, W Cheung, P Maitz, D Milliss, G Thanakrishnan and F Li A new framework for analysis and prevention strategies of severe burns and injuries in NSW D Goltsman, Z Li and P Maitz Skin Tissue Engineering: Producing the Ideal Electrospun Scaffold with Optimal Skin Cell Culture Conditions for Cellular Interactions C Chong, Y WanG, P Maitz and Z Li Study of skin graft contraction V llie, Y Wang, Z Li and P Maitz The role of androgens in wound healing-design of a new wound dressing material to accelerate healing process Y Wang, K Cheer, P Maitz and Z Li in collaboration with U Simanainen and D Handelsman (Andrology Laboratory, ANZAC Research Institute) A randomised and double-blinded trial to investigate the effects of Clobetasol Propionate cream on skin grafts for burn wounds R Hilmi, R Johnson, Z Li, S Zagarella and P Maitz Defining the effects of herpes simplex virus infection on human gamma delta T cells U Yu, M Fernandez, A Ferguson, A Cunningham, M Kim, S Alexander , A Holland, P Maitz, Z Li and C Jones Investigation of novel skin wound healing materials in an in vitro human skin equivalent model. B Farrugia, M Lord, P Maitz, Z Li and J Whitelock Ablative fractional CO2 laser for the treatment of severe burns scars A Issler-Fisher, F Li, O Fisher, M McSweeney, P Haertsch, Z Li and P Maitz Post burn scar maturation F Li, P Maitz and Z Li Comparative study of cross-linked vs non cross- linked dermal regenerative scaffolds in wound contraction J Beekman, F Suarez, A Fathi, C Chong, Y Wang, P Maitz, PVan Zuijlen and Z Li Early management of burns S Lajevardi, P Kennedy and P Maitz

Biennial Report 2013-15 15 Dendritic Cell Research

BASIC DC DISCOVERY RESEARCH Antibody engineering to produce “custom made” reagents G Clark, D Hart, Z Elgundi The potential to control inflammation by modulating CD300a and CD300c biomarkers G Clark, R Gasiorowski, D Hart CD300f as a target for the treatment of acute myeloid leukaemia Robin Gasiorowski, G Clark, D Hart, K Bradstock Determining the function of CD302 P Silveira, K Lo, N Verma, A Vu, G Clark, D Hart

DC IN HAEMATOLOGICAL DISEASES Translation of human blood dendritic cell subset biology in multiple myeloma P Fromm, C Bryant, F Kupresanin, J Hsu, D Hart Collaborators: H Suen, R Brown, D Joshua Ten year survivors of multiple myeloma demonstrate differing expression of immune biomarkers C Bryant, D Hart, P Fromm Collaborators: H Iland, JGibson, R Brown, S Yang, H Suen, PJ Ho Dysfunctional antigen presentation by malignant multiple myeloma plasma cells changes cytotoxic effector T-cells into acquired regulatory cells D Hart, P Fromm Collaborators: J Gibson, R Brown, S Yang, H Suen, P J Ho

GRAFT VERSUS HOST DISEASE Identification of blood DC biomarkers that predict the development of acute and chronic graft versus host disease following bone marrow transplantation K Shahin, Z Mattar, D Hart, K Bradstock Collaborators: M Sartor, S Larsen, L Bendall Modulation of dendritic cell function through extracorporeal photophoresis in the treatment of chronic graft versus host disease P Fromm, F Kupresanin, G Clark, D Hart Collaborators: H Suen, R Brown, S Larsen, J Gibson, D Joshua

16 Biennial Report 2013-15 The use of anti-CD83 antibodies as novel immunosuppressive agents X Ju, Blake Hsu, N Verma, P Silveira, A Vu, K Shahin, P Fromm, G Clark, K Bradstock, D Hart

IMMUNOTHERAPY mRNA loading of tumour associated antigens into blood dendritic cells P Fromm, J Hsu, M Papadimitrious, C Bryant, F Kupresanin, G Clark, D Hart Collaborators: S Anguille, E Newman, I Cunningham, Z Berneman, L Horvath

Geriatric Epidemiology

Measuring Steroids in Serum and Biological Samples R Desai, T Harwood, P Keski-Rahkonen and DJ Handelsman Ageing, nutrition and the geometric framework Cumming R, Simpson S, Le Couteur D, Blyth F, Naganathan V, Kendig H, Seibel M Study of the relationship of oral health and oral health service utilisation to the general health of older Australian men Cumming RG, Wright FC, Hirani V, Naganathan V, Blyth F

Northcott Neuroscience Laboratory

Gene Discovery Program for Inherited Peripheral Neuropathies M Kennerson, M Brewer, A Drew, M Ellis, A Grant, A Kidambi, C Ly, J Qi, G . Nicholson Motor Neuron Disease (MND) and Disorders G Nicholson Worm models for Inherited Peripheral Neuropathies M Brewer, A . Siddell, G . Nicholson, M . Kennerson Cell models of Inherited Peripheral Neuropathies G Perez-Siles, M . Ellis, A . Grant, A . Kidambi, C . Ly, A .Siddell, G . Nicholson, M . Kennerson Zebrafish models of Machado Joseph Disease A Laird, K Yuan, N Mackovski, G Nicholson

Biennial Report 2013-15 17 Vascular Biology

Exploring the Effect of Colchicine on Platelet Function G Pennings, M Traini, C Reddel, V Chen, L Kritharides A quantifiable role for microparticles in global coagulation and fibrinolysis and mechanisms of their release in patients with coronary artery disease C Reddel, G Pennings, J Curnow, V Chen, L Kritharides Cardiac dysfunction after pulmonary embolism and after clozapine V Chow, L Kritharides Remote ischaemic preconditioning and its effect on coronary physiology and platelet & leukocyte activation (RIPPLE Study) J Lau, A Yong, G Pennings, H Campbell, V Chen, L Kritharides Novel Measures of Haemostatic Function in cardiovascular and other diseases C Reddel, R Alcock, J Curnow, D Breiger, V Chow, G Pennings, V Chen, L Kritharides Novel intravascular (within arteries) imaging using Optical Coherence Tomography (OCT) H Lowe, G Pennings Choice of Health Options In Preventing Cardiac Events (CHOICE Study) B Freedman, J Redfern, L Neubeck .

Platelet and Thrombosis Research Laboratory

Development of a novel assay for measurement of procoagulant platelets L Pasalic, H Campbell, V Chen Procoagulant platelets in coronary artery disease: GSAO as a biomarker for coronary artery disease. L Pasalic, H Campbell, V Chen Cell death pathways in procoagulant platelet formation. E Glaros, V Chen Procoagulant platelets in sepsis: a pilot study L Pasalic, J Iredell, M O’Sullivan, V Chen Clotwave form analysis for assessment of bleeding disorders G Kershaw, L Khoo, S Dunkley, V Chen

18 Biennial Report 2013-15 Highlights & Prizes

Adrenal Steroid • Dr Jinwen Tu: Amgen-ANZBMS Outstanding Abstract Award 2014 • Dr Jinwen Tu: ANZBMS Travel Award 2014

Andrology • Sydney Research Awards 2015- Supervisor Award- Dr Kirsty Walters • Society for Reproductive Biology Emerging Research Leader Award 2015- Dr Kirsty Walters • University of Sydney Early Career Researcher Overseas Travel Grant 2014- Dr Kirsty Walters • Life Member, Society of Reproductive Biology 2015- Prof David Handelsman • Fellow, Australian Academy of Medical and Health Sciences 2015- Prof David Handelsman

Atherosclerosis • In 2013, our work on the atherogenic side effects of the immunosuppressant drug Cyclosporin A was internationally recognized by an invitation to Professor Kritharides speak at the International Symposium on Cyclophilins and other Foldases . • Together with the members of the Vascular Biology Group, the Atherosclerosis Laboratory organized the 13th ANZAC Research Institute annual symposium: ‘Contemporary Issues in Atherosclerosis, Thrombosis and Coronary Disease’ . • In 2014, Leonard Kritharides and Wendy Jessup were the joint recipients of the Distinguished Lecturer Award from the Australian Vascular Biology Society (AVBS) . This was only the fourth presented in the 22 year history of the AVBS . • Leonard Kritharides and Wendy Jessup were awarded the Australian Vascular Biology Society (AVBS) Distinguished Lecturer Award

Biogerontology • David Le Couteur was awarded the 2014 Don Beaven Travelling Fellowship and Athol Mann Lecturer, Christchurch NZ • Publications in Cell Metabolism, PNAS and Cell Reports, with editorials in Science and many newspapers.

Bone Biology Our group is well represented at national and international scientific meetings (e .g . American Society for Bone and Mineral Research (ASBMR); International Conference on Children’s Bone Health (ICCBH); Australian and New Zealand Bone and Mineral Society (ANZBMS); Australian & New Zealand Obesity Society (ANZOS) and others) . At all of these meetings, our group has had multiple oral presentations, reflecting the high standard and international recognition of our research . In 2014, our group’s research has been selected for eight oral presentations at international and national conferences .

• Prof Markus Seibel: Elected President of the Australian and New Zealand Bone & Mineral Society (2013- 2015)

Biennial Report 2013-15 19 • Prof Markus Seibel: Invited Member, Publications Committee of the American Bone and Mineral Society (2015 – 2018) • Prof Hong Zhou: Re-elected ICMRS Chair of Board Directors for 2013-2015 • Dr Yu Zheng: Cancer Institute NSW Career Development Fellowship (2014 -2017). • Dr Konstantin Horas: DFG Postdoc Fellowship award 2013-2015 • Dr Konstantin Horas: CRGH Early Career Research Prize 2014 • Dr Konstantin Horas: ANZBMS Travel Award 2014 • Dr Jinwen Tu: Amgen-ANZBMS Outstanding Abstract Award 2013 • Dr Jinwen Tu: ANZBMS Travel Award 2013 • Dr Jinwen Tu: Amgen-ANZBMS Outstanding Abstract Award 2014 • Dr Jinwen Tu: ANZBMS Travel Award 2014 • Dr Holger Henneicke: International Postgraduate Research Scholarship (IPRS) 2012-2015 • Dr Holger Henneicke: Australian Postgraduate Award (APA) 2012-2015 • Dr Holger Henneicke: International Postgraduate Award 2012-2015 • Dr Holger Henneicke: Young Investigator Award, ICCBH 2013, Rotterdam, Netherlands • Dr Holger Henneicke: Runner-Up, Sydney Lifespan Symposium 2014, Sydney, Australia • Dr Holger Henneicke: : Young Investigator Award, ASBMR 2014 • Dr Holger Henneicke: ANZBMS Travel Award 2014 • Dr Holger Henneicke: Poster Award, German Society for Osteology Annual Meeting 2015 • Sylvia Gasparini: Australian Postgraduate Award (APA) 2013-2015 • Sylvia Gasparini: ANZBMS Travel Award 2014 • Sylvia Gasparini: Early Career Researcher Award, ANZOS Annual Meeting 2014 • Sarah Kim: Australian Postgraduate Award (APA) 2014-2016 • Sarah Kim: ANZBMS Travel Award 2014 • Shihani Stoner: ANZBMS Travel Award 2014

Dendritic Cell Research • Nirupama Verma: CRGH Research Travelling Scholarship 2014 • Michael Papadimitrious: Arrow Hawkesbury Canoe Classic PhD Scholarship 2014 • Michael Papadimitrious: The Charles Perkins Centre and Marie Bashir Institute for infectious disease and Biosecurity 2014 • Pablo Silveira: USY D / NHMRC Equipment Grant 2014 ??????? • Pablo Silveira: SPARC Grant 2014 ?????? • Michael Papadimitrious: AAI Trainee Abstract Award 2015 • Christian Bryant: Sydney Catalyst 3 minute thesis competition 2015 • Phillip Fromm: Rebecca Cooper Foundation Influx Upgrade 2015 ???

Vascular & Platelet and Thrombosis Research • Dr Vincent Chow graduated with his PhD from the USyd and was a finalist for the Concord Clinical Week prize . Dr Richard Alcock graduated with his Masters from the USyd . Dr Chris Naoum, Dr Michael Chang and Nicole Lowres have all submitted their theses .

20 Biennial Report 2013-15 • Dr Gabrielle Pennings and Dr Caroline Reddel were both awarded with USyd Kickstart Grants and Dr Caroline Reddel received two travel awards from the Sydney Medical School and Concord Repatriation General Hospital Research Committee to attend the ISTH 2013 Congress in Amsterdam and to attend the ISTH 2015 Congress in Toronto . • Australian Provisional patent filed for “Selective targeting of procoagulant platelets” by Dr Vivien Chen and her group . • Leonard Kritharides and Wendy Jessup were awarded Australian Vascular Biology Society (AVBS) Distinguished Lecturer Award • Gabrielle Pennings: USyd Kickstart (ECR & New Staff) Grant recipient • Caroline Reddel: USyd Kickstart (ECR & New Staff) Grant recipient; CRGH Research Travel Grant and Sydney Medical School Early Career Researcher Overseas Travel Grant 2013

Northcott Neuroscience Laboratory • We have shown the importance of structural variation (SV) as a disease causing mechanism for a form of X-linked CMT (CMTX3) . A 78-kb region of chromosome 8 has been inserted into the CMTX3 disease region and causes a change in gene dosage . The study of SV is an important initiative for our research to determine the contribution of pathogenic DNA re-arrangements as a cause of CMT . • We have demonstrated important molecular pathogenic changes in a mouse model for X-linked distal motor neuropathy . The mutated Atp7a copper transporter expressed in the mouse model shows trafficking defects and reduced protein mutant protein . This model will be a key resource to develop copper based therapies to prevent motor neuron degeneration . • This year we commenced a pilot trial in herditary sensory neuropathy type 1 (HSN1) which is a motor and sensory neuropathy (a form of CMT) . This disease is caused by a mutation in a gene (serine palmioyl transferase) discovered by our group . The gene mutation results in production of a neurotoxic sphingolipid . The toxin be reduced by a dietary supplement serine . The pilot trial is developing measures to asses the treatment . • A/Prof Marina Kennerson was invited to teach a Gene Mapping Course (Find that Gene!) for researchers and postgraduates at the University of Malaya in 2014 . She is also an invited lecturer for second and and fourth year Biomedical Science students at University of Malaya (2014) and University of Newcastle (2015) . A/Prof Kennerson was also invited to do Bioinformatics lecture series for Sydney Local Health District (2015) . • The group has been part of an initiative to bring together researchers in neuropathy across Sydney and participated in the inaugural Sydney Neuropathy Research Group (SyNRG) which is part of the Neuroscience Network at Sydney University . Our group contributes genomics/bioinformatics expertise and excellence in gene discovery skills . • Professor Nicholson is on the advisory board of the Inherited Neuropathy Consortium of the USA and is medical advisor to the CMT Association of Australia and is the patron of the MJD Foundation of Australia . • Megan Brewer, Tony Basten Fellowship Scheme, Sydney Medical School, University of Sydney, $50,000 • Megan Brewer, CRGH Travel Fellowship, Sydney Local Health District, $2000 • Megan Brewer, Annual Health Research Infrastructure Award, Sydney Research, Sydney Local Health District, $10,000 • Gonzalo Perez-Siles, Early Career Research Award , Sydney Neuropathy Research Group (SyNRG) , $250 • Alex Drew, Multi-disciplinary Collaborative Research Projects, Sydney Neurosciences Network, University of Sydney $10,000

Biennial Report 2013-15 21 Collaborations: Summary

Andrology Australia AstraZeneca, UK- New Opportunities Group Australian Institute of Bioengineering and Nanotechnology Baker IDI, Melbourne, Metabolomics Blood and Marrow Transplant Service, Westmead Hospital Bosch Institute Boston Medical Cente, Boston, USA Boston University Brain and Mind Institute Burnett Research Institute Burns Centre, Red Cross Hospital, Beverwijk, the Netherlands Busheer University, Busheer, Iran Cambridge University Centenary Institute Charles Perkins Centre, University of Sydney Children’s Cancer Institute Australia Children’s Hospital at Westmead Children’s Medical Research Institute, Sydney Chinese University of Hong Kong Chris O’Brien Lifehouse Concord Cancer Centre Concord Repatriation General Hospital, Haematology Department Concord General Repatriation Hospital Deakin University, Melbourne Elastagen Pty Ltd Garvan Institute of Medical Research Harvard Medical School, USA- Department of Genetics Heart Research Institute Humboldt University Berlin, Germany Indiana University, Indiana, USA INSERM UPMC 1166, Paris, France Institute of Reproductive & Developmental Biology, Imperial College London, London, UK Kolling Institute, The Ageing Pharmacology Laboratory Kolling Institute of Medical Research, University of Sydney Laboratory for Ageing Research, UNSW Leiden Academic Centre for Drug Research, Netherlands Leiden University Medical Centre, Netherlands Macquarie University, Faculty of Science and Engineering

22 Biennial Report 2013-15 Macquarie University Melbourne Pathology Menzies Research Institute Tasmania Monash University Murdoch Childrens Research Institute Nanjing Medical University, China National Institutes of Health, USA National Institute of Ageing, NIH, USA National Measurement Institute New England Research Institute, Boston, USA NHMRC Clinical Trials Centre North Western Polytechnical University, China Peter MacCallum Cancer Centre Prince Henry’s (Hudson) Institute of Medical Research, Monash University Royal College of Pathologists of Australasia/Australasian Association of Clinical Biochemists Prince of Wales Hospital Royal North Shore Hospital Royal Perth Hospital, Medical Engineering & Physics Royal Prince Alfred Hospital Royal Prince Alfred Hospital, Institute of Haematology Rush University, USA Schizophrenia Research Institute, Neuroscience Research Australia Shanghai University of Traditional Chinese Medicine, China Shanghi Jiaotong University, China Shihezi University School of Medicine, China Southern Cross Pathology Australia, Monash Medical Centre Southwestern Medical Center, Dallas USA . Stanford University Medical Center St Vincent’s Hospital, Sydney St Vincent’s Hospital, Melbourne University of Adelaide University of Antwerp, Belgium University of Birmingham, UK University of Birmingham, UK Respiratory Research Unit University of Birmingham, UK Rheumatology Research Unit University of Copenhagen, Denmark University of Leeds, UK- Endocrinology University of Malaya University of Melbourne University of Miami University of Michigan, Ann Arbor USA

Biennial Report 2013-15 23 University of New South Wales University of New South Wales, Faculty of Medicine University of New South Wales - School of Biotechnology and Biomolecular Sciences, University of Otago, New Zealand University of Queensland University of Sheffield, UK - Bone Research Group University of Sydney University of Sydney, Central Clinical School University of Sydney - School of Molecular Bioscience, Discipline of Pathology, School of Medical Sciences and Charles Perkins Centre University of Tasmania, Hobart University of Technology Sydney University of Turku, Finland University of Ulm, Germany University of Washington, Seattle, USA University of Western Sydney Walter and Eliza Hall Institute Westmead Hospital Westmead Millennium Institute for Medical Research Westmead and the Millenium Research Institute, Institute for Clinical Pathology and Medical Research Yale University, USA University of New South Wales University of New South Wales, Faculty of Medicine University of New South Wales - School of Biotechnology and Biomolecular Sciences, University of Sheffield, UK - Bone Research Group University of Technology Sydney University of Ulm, Germany University of Western Sydney Walter and Eliza Hall Institute Westmead Hospital Westmead Millennium Institute for Medical Research Westmead and the Millenium Research Institute, Institute for Clinical Pathology and Medical Research Yale University, USA

24 Biennial Report 2013-15 Staff & Students 2013-2013

Scientific Staff

Director Project Managers Professor David Handelsman MBBS, PhD, FRACP Jane Mc Donald Research Scientists Scientific Program Leaders Dr Megan Brewer PhD Professor Mark Cooper MD, PhD Dr Vivien Chen MBBS, BA, PhD, FRACP FRCPA Professor Bob Cumming MBBS, MPH, PhD, FAFPHM Reena Desai BSc, MSc Professor Ben Freedman MBBS, FRACP, FACC, FESC, Dr Alex Drew PhD PhD Dr Zehra Elgundi PhD Professor David Handelsman MBBS, PhD, FRACP Dr Phillip Fromm PhD Prof Derek Hart MBChB, FRCS, PhD, FRCPA, FRACP Mark Jimenez BSc (Hons) Professor David Le Couteur MBBS, PhD, FRACP Dr Maaike Kockx PhD Professor Peter Maitz AM,MD, PhD, FRACS Dr Angela Laird PhD Professor Garth Nicholson MBBS, PhD Dr Lam Ly MD (Vietnam), PhD Professor Marc Gladman MBBS, DRCOG, DFFP, PhD,MRCOG,FRCS Dr Donna Marcal PhD Professor Markus Seibel MD, PhD, FRACP Dr Gabrielle Pennings PhD Professor Len Kritharides MBS, FRACP, FAHA, PhD Dr Gonzalo Perez PhD Dr Caroline Reddel PhD Clinical Research Associates Dr Kifah Shahin PhD Dr Ulla Simanianen PhD Professor Ken Bradstock MBBS, PhD Jenny Spaliviero MSc A/ Professor David Brieger MBBS, FRACP, PhD Dr Pablo Silveira PhD A/ Professor Ann Conway MBBS, FRACP Dr Marion Stoll PhD Dr Peter Haertsch AM,MBBS, FRACS, FRCS Edin Dr Matthew Triani PhD Dr Peter Kennedy AM, MBBS, MDS, FRACS Dr Jinwen Tu PhD Research Fellows Dr Niruparma Verma PhD Dr Yiwei Wang Grad Dip Pharm . Sciences PhD Dr Charles Allan PhD Dr Allesandra Warren MSc PhD A/ Professor Georgina Clark BSc (Hons1), PhD Dr Yu Zheng BMed, MMed, PhD Dr Victoria Cogger PhD A/Professor Marina Kennerson PhD Clinical Research Nurses Dr Aisling McMahon PhD Glenda Fraser RN A/Professor Harry Lowe MBBS, FRACP, FACC, PhD Jane Summers RN Professor Wendy Jessup BSc (Hons), PhD Leo Turner RN Dr Kirsty Walters PhD Dr Wei Zhao MD (China), PhD Dr Andy Yong MBBS, PhD, FRACP, FCSANZ Professor Hong Zhou MD (China), PhD Research Assistants Shu Oi Chow BSc (Hons) Melina Ellis BSc(Hons),Grad DipEd Sc

Biennial Report 2013-15 25 Kate Flinders Mari Wright Colette Fong-Yee BSc, MSc (Hons) James Zagarella Francia Garces Surarez BSc (Hons) Dr Danqing Zhu PhD Megan Honeyman BSc Ben Hsu MSc Overseas Visiting Fellows/Students Xinsheng Ju MD, MMed Sc Yunzhao Chen Aditi Kidambi BSc (Hons) Mingxuan Gao Raani Kumaran BSc (Hons) Diana Hide Ashkan Javadzadegan PhD Konstantin Horas Fiona Kupresanin BBiomedSc, Mdiet Jasan Ji Mandy Leung Dianlian (Harry) Lin Carolyn Ly BMedSc (Hons) Rick Nolte Nick Mackovski BSc (Hons) Janko Sattler Linda Middleton BSc (Hons) Tung Biu Thanh Leticia Muusers BSc Tingyu Wang Diana Nawara BSc (Hons) Jody O’Connor BHealthSc, MPH Graduate Students Jennifer O’Reilly PhD Dr Malcolm Anastasius MBBS(Hons) MMed, FRACP Alexandra Porter DAA Dr Christian Bryant MBBS, FRACP, FRCPA Joanne Tai Lee BSc (Hons) Aimee Caldwell BSc (Hons) Phi Ai Vu BSc (Hons) Rabia Chaudhry BSc (Hons) Lucy Yang MD Peter Choi BSc (Hons) Kristy Yuan Cassandra Chong BSc (Hons) Ling Zhuang Dr Vincent Chow MBBS, FRACP,PhD Ellen Gao BSc Technical Support Dr Robin Gasiorowski MA, MBBS, FRACP, FRCPA Ann Aziz MSc Sylvia Gasparini BSc (Hons) Fay Bacha BSc Rasmani Hazra BSc Frank Bathur BSc, MHA Dr Holger Henneicke MD Annette Berryman Jonathan Hew BmedSc Dr Lisa Bridgett PhD Blake Hsu MBChB Donna Bonnici Gurmeet Kaur MSc Shannon Chu MSc Sarah Kim BSc (Hons) Guy Dernee Dr Jerret Lau MBBS, FRACP Irene Di Pierro Dip Sc Kevin Lo BMedSc (Hons) Adrienne Grant BA (USA) Nicole Lowres BSc (Physio) Patty Kapeleris Business Studies Mashani Mohamad MSc Alev Kavakci Michael Papadimitrious BSc (Hons) Zamil Mattar BSc Shajjia Razi BSc, MSc Tyler McClelland Kheng-Seone Ng BSc Khim Perkins Anna Siddel BSc (Hons) Dr Lyn Schedlick BSc PhD Shihani Stoner MSc Ljubica Vrga BSc (Hons) Danielle Upton BSc Matilda Webbey Animal Attendant Cert 3 Dr Frank Zhang MBBS(Surg) Joshua Webbey

26 Biennial Report 2013-15 Honours Students Administrative Staff

2014 Director Renz Alingcastre Professor David Handelsman MB BS, PhD, FRACP Anthony Cutrupi Director, Laboratory Animal Services (MPU), Concord Campus . 2015 Mamdouh Khalil BSc, Ass Dip Animal Technology Claudia Alamein Business Manager Nicolas van Kooten Losis Jessica Qi Julie Taranto JP, BSc

Masters Students Finance Manager Peter Cao BSc (Hons) Annet Doss, Dip Acc, Grad Cert in Acct & Fin Mgmt Nandini Shankara Narayana MBBS Accounts Clerks Summer Scholars Candice Chang Hannah Dong 2013/14 Information Systems Manager Michael Efundy Stephanie Eid Justin Crosbie BSc Infor Tech, MHSM Kieran English Alexander Gillis Human Resources Manager(s) Kevin Leow Rachelle Innes Dip Bus (HR), BA(Psych) Riddhi Patel Jeremy Qiao Receptionist/Administration Nina Sulkowski Tracey Dent Maria Wilkins

2014/15 Nicole Khor Raymond Li William Lukito Jessica Qi Jeremy Qiao Alma Wu Jessica Zhou

Biennial Report 2013-15 27 Grants & Contracts 2013-2015

(Annualised $)

New Grants Andrology Australia- Training Fellowship . Marren . $15,000 Astra Zeneca Pty Ltd: Brieger . “New data base, approved sites & recruited patients ”. $500,000 Cancer Australia: Seibel, Zhou, Zheng, Dunstan . “Novel Cytoplasmic Functions of the Vitamin D Receptor in Bone Metastases ”. $119,891 Cancer Australia- Collaborative Cancer Research Scheme: Zheng . “Mechanisms of self-amplification and tumour growth in breast and prostate cancer metastases to bone ”. $85,004 Cancer Institute NSW- Career Development Fellowship: Zheng . “Characterization and Functional Analysis of the Vitamin D Receptor Isoforms and their Role in Breast Cancer Progression: Experimental and Human Translational Studies ”. $198,000 Heart Foundation: Lowres . “Screening Education and Recognition in Community Pharmacies of Atrial Fibrillation (SEARCH-AF) for Stroke Prevention ”. $26,903 Heart Foundation- Future Leader Fellowship: Yong . “Wireless fractional flow reserve measurement using computational fluid dynamics analysis during coronary angiography “ $94,000 Heart Foundation-Vanguard: Freedman, Neubeck, Peiris, Lowres . “GP SEARCH_AF ”. $75,000 NHMRC- Program: Barter, Celermajer, Rye, Kritharides, Jessup . “Atherosclerosis- the key roles of HDL, cell cholesterol metabolism and vascular function ”. $566,800 NHMRC: Handelsman, Harwood, Keski-Rahkonen . “Development and application of a novel ultrasensitive LC-MS estradiol assay ”. $119,396 NHMRC: Kennerson, Nicholson . “Gene identification for inherited peripheral neuropathies applying next generation sequencing ”. $195,116 NHMRC: Cumming, Wright, Hirani,Naganathan, Blyth Harford . “Study of the relationship of oral health and oral health service utilisation to the general health of older Australian men ”. $153,241

28 Biennial Report 2013-15 NHMRC: Laird, Nicholson, Becker, Giacomotto . “Seeking a cure for Machado Joseph disease- a prevalent neurodegenerative disease in North east Arnhem Land ”. $142,112 NHMRC: Zhou. “Are Chondrocytes the Target Cells of Glucocorticoid Therapy in Serum-Induced Autoimmune Arthritis?” $174,167 NHMRC: Lau . “Remote ischaemic preconditioning and its effect on coronary physiology and platelet and leukocyte activation ”. $40,057 NHMRC: Seibel, Zhou, Osborne, Swarbrick. “How Does Osteocalcin Reverse Glucocorticoid-Induced Dysmetabolism?” $206,743 NHMRC Equipment Grant: Le Couteur . “EVOS® FL Auto cell imaging system ”. $55,000 NHMRC Scholarship: Gasiorowski . “The translation of dendritic cell biology into clinical practice ”. $27,529 Philip Bushell Foundation: Freedman, Neubeck, Orchard, Lowres . “An iPhone screening program in general practice for atrial fibrillation to prevent stroke ”. $94,143 RACP- Sir Roy McCaughey Fellowship: Yong . “Wireless fractional flow reserve measurement using computational fluid dymanics analysis during coronary angiography ”. $35,000 RCPA Foundation: Bryant . “The Identification of a Novel CD2 high Plasmacytoid Dendritic Cell Subset in Human Tissues ”. $5,000 RCPA Foundation: Gasiorowski . “Novel antibody targets in Acute Myeloid Leukaemia ”. $5,000 Rebecca L Cooper Equipment: Cooper . “Role of hypothalamic glucocorticoid sensitivity in the development and severity of inflammatory arthritis ”. $22,000 Rebecca L Cooper Equipment: Hart . “Low Side Effect Therapy For Malignancies In The Elderly ”. $22,000 Sydney Catalyst: Fromm . “mRNA prostate cancer antign loaded blood dendritic cell therapy ”. $50,000 Sydney Medical School: Wang . “A Novel Elastin-based Skin Substitute in Wound Healing ”. $25,000 University of Sydney: “MoU ”. $1,083,141 University of Sydney-Equipment: Hart, Handelsman, Seibel, Kritharides, Nicholson . “X-RAD 320 Irradiator ”. $200,000 USyd- ECR: Reddel . “A quantifiable role for microparticles in global coagulation, fibrinolysis and mechanisms of their release in patients with coronary artery disease ”. $25,000 USyd/ ARI Bridging Scheme: Simanainen, Handelsman, Zheng . “Androgen signalling as a therapeutic target in breast cancer ”. $60,000 USyd/ ARI Bridging Scheme: Allan, Handelsman . “Dissecting the somatic control of hormone-regulated spermatogenic development ”. $60,000 USyd/ ARI Bridging Scheme: Zhou, Seibel, Cooper, Stewart . “Age-associated changes in body composition and fuel metabolism: The role of the osteoblast and endogenous glucocorticoid signalling ”. $60,000 USyd Bridging Scheme: Walters, Smith, Handelsman, Allan . “Androgen receptor mediated regulation of female reproduction ”. $30,000 USyd Bridging Scheme: Le Couteur, Cogger, Simpson, McMahon, Hilmer . “Fenestrations and the hepatic disposition of insulin in health, ageing and disease ”. $60,000 USyd Bridging Scheme: Seibel, Zhou, Speranza, Cogger . “How Does Osteocalcin Reverse Glucocorticoid-Induced Obesity and Fatty Liver?” $30,000 USyd Bridging Scheme: Allan, Walters . “FSH control of follicle and oocyte development ”. $60,000

On-going Grants ARC- Discovery Early Career Researcher Award: Walters . “Androgens and ovarian Function ”. $125,000 Bayer HealthCare: Freedman . “SEARCH-AF Stoke prevention study ” $35,200

Biennial Report 2013-15 29 Cancer Australia/NHMRC: Hart , Bradstock . “RNA loading of tumor associated antigens and the activation of blood dendritic cells for cancer immunotherapy ”. $26,027 Cancer Institute NSW- Career Development & Support Fellowship: Hart . “The translation of dendritic cell biology into new cancer therapies “. $199,897 Cancer Institute NSW: Translational Grant: Hart, Bradstock, Joshua . “Enabling Diagnostic and Therapeutic Antibodies for Haematological and other Malignancies ”. $708,693 Charcot-Marie-Tooth Association of Aust: Kennerson, Perez, Nicholson . “Using Cultured Primary Motor Neurons and Peripheral Nerves to Study the Consequences of ATP7A Mutations in Distal Hereditary Motor Neuropathy ”. $12,000 MDA: Nicholson, Kennerson . “Determining the pathogenic effects of ATP7A Mutations in distal motor neuropathy ”. $140,000 MJD Foundation: Nicholson . “Establishment of a model phenotype suitable for Machado-Joseph disease (MJD) drug screening ”. $192,000 NHMRC: Seibel, Zhou, Gundberg, Dunstan . “Role of osteoblast in mediating glucocorticoid-induced metabolic dysfunction ”. $211,719 NHMRC: Zhou, Seibel, Stewart, Buttgereit, Cooper . “Role of endogenous glucocorticoids in inflammatory arthritis ”. $177,850 NHMRC: Cumming, Simpson, Le Couteur, Blythe, Naganathan, Kendig, Seibel . “Aging, nutrition and the Geometric Framework ”. $184,632 NHMRC- Fellowship: Zheng . “Vitamin D Deficiency and Breast Cancer Metastasis to Bone ”. $41,448 NHMRC: Allan, Handelsman, Walters, Howell . “FSH control of ovarian function ”. $213,513 NHMRC: Simanainen, Handelsman . “Intraprostatic androgen signalling as a target in prostate cancer ”. $126,195 NHMRC: Nicholson, Kennerson . “Discovery of Genes For X-linked Charcot-Marie-Tooth Neuropathy ”. $139,216 NHMRC: Blair, Nicholson . “Investigating the genetic basis of ALS “. $137,508 NHMRC- Training Fellowship: Brennan-Speranza . “The influence of cortisone on the synthesis and signaling of osteoblastic-derived mediators of metabolic dysfunction ”. $15,921 NHMRC- Clinical Research Fellowship: Yong . “Studying Coronary Physiology within Human Coronary Arteries using Computational Fluid Dynamics ”. $87,508 NHMRC- Program: Hart, Bradstock . “The translation of dendritic cell biology into clinical practice ”. $672,000 NHMRC- Research Fellowship: Hart . “Clinical translation and commercialisation of novel therapeutic interventions in haematological malignancy and ASCT ”. $181,329 NHMRC: Walters . “Role of androgens in polycystic ovary syndrome ”. $151,830 NHMRC: Wittert, Yeap, Grossman, Conway, Allan, Kaye, Jenkins,Daniel . “Testosterone intervension for the prevention of dibetes mellitus in high risk men: a randomised trial ”. $88,000 OMR- Infrastructure: “Funding 2012-16” $824,402 Philip Bushell Foundation: Witting. “Can specific inhibitors of inflammation improve heart function qafter heart attack?” $24,000 USyd- Grant-In-Aid: Witting, Freedman, Geczy . “Approaches to inhibit SAA-induced endothelial dysfunction and atherosclerosis ”. $65,000 USyd- Early Career Research Scheme: Zheng . “Novel cytoplasmic functions of the Vitamin D receptor in prostate cancer and its bone metastases ”. $25,000 USyd Equipment Grant: Seibel, Handelsman, Le Couteur, Hart, Nicholson, Freedman, Kritharides, et al . “An IVIS Lumina II in vivo Imaging System ”. $200,000 USyd Equipment Grant: Hart, Handelsman, Le Couteur, Nicholson, Kritharides, et al . “Automacs Pro Separator ”. $68,000

30 Biennial Report 2013-15 Publications

Acosta JR, Goldsbury C, Winnick C, Badrock AP, Brown R, Yang S, Weatherburn C, Gibson J, Ho PJ, carcinogenesis . Breast Cancer Res 16 (6): 483, 2014 . Fraser ST, Laird AS, Hall TE, Don EK, Fifita JA, Blair Suen H, Hart D and Joshua D PMID:25928046 IP, Nicholson GA and Cole NJ Phospho-flow detection of constitutive and cytokine- Mutant human FUS Is ubiquitously mislocalized and induced pSTAT3/5, pAKT and pERK expression Chow V, Feijo I, Trieu J, Starling J and Kritharides L generates persistent stress granules in primary cultured highlights novel prognostic biomarkers for patients with Successful rechallenge of clozapine therapy following transgenic zebrafish cells . PLoS One 9 (6): e90572, multiple myeloma . Leukemia 29 (2): 483-490, 2015 . previous clozapine-induced myocarditis confirmed on 2014 . PMID:24912067 PMID:24990616 cardiac MRI . J Child Adolesc Psychopharmacol 24 (2): 99-101, 2014 . PMID:24521168 Alcock RF, Yong AS, Ng AC, Chow V, Cheruvu C, Bryant C, Suen H, Brown R, Yang S, Favaloro J, Aklilu Aliprandi-Costa B, Lowe HC, Kritharides L and E, Gibson J, Ho PJ, Iland H, Fromm P, Woodland N, Chow V, Ng AC, Chung T, Thomas L and Kritharides L Brieger DB Nassif N, Hart D and Joshua DE Right atrial to left atrial area ratio on early Acute coronary syndrome and stable coronary artery Long-term survival in multiple myeloma is associated echocardiography predicts long-term survival after disease: are they so different? Long-term outcomes in a with a distinct immunological profile, which includes acute pulmonary embolism . Cardiovasc Ultrasound 11 contemporary PCI cohort . Int J Cardiol 167 (4): 1343- proliferative cytotoxic T-cell clones and a favourable 17, 2013 . PMID:23725312 1346, 2013 . PMID:22534045 Treg/Th17 balance . Blood Cancer J 3 e148, 2013 . PMID:24036947 Chow V, Ng AC, Seccombe L, Chung T, Thomas L, Aliprandi-Costa B, Ranasinghe I, Turnbull F, Brown Celermajer DS, Peters M and Kritharides L A, Kritharides L, Patel A, Chew D, Walters D, Rankin Bunker DJ, George RJ, Kleinschmidt A, Kumar RJ Impaired 6-min walk test, heart rate recovery and J, Ilton M, Meredith I, Cass A and Brieger D and Maitz P cardiac function post pulmonary embolism in long- The design and rationale of the Australian Cooperative Alkali-related ocular burns: a case series and review . J term survivors . Respir Med 108 (10): 1556-1565, 2014 . National Registry of Acute Coronary care, Guideline Burn Care Res 35 (3): 261-268, 2014 . PMID:23877138 PMID:25154698 Adherence and Clinical Events (CONCORDANCE) . Heart Lung Circ 22 (7): 533-541, 2013 . PMID:23415708 Cai X, Freedman SB and Witting PK Chow V, Reddel C, Pennings G, Chung T, Ng AC, Serum amyloid A stimulates cultured endothelial cells Curnow J and Kritharides L Banks E, Joshy G, Abhayaratna WP, Kritharides L, to migrate and proliferate: inhibition by the multikinase Persistent global hypercoagulability in long-term Macdonald PS, Korda RJ and Chalmers JP inhibitor BIBF1120 . Clin Exp Pharmacol Physiol 40 (9): survivors of acute pulmonary embolism . Blood Coagul Erectile dysfunction severity as a risk marker for 662-670, 2013 . PMID:23819722 Fibrinolysis 2015 . PMID:25811450 cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study . PLoS Med 10 (1): Caldwell AS, Eid S, Kay CR, Jimenez M, McMahon Chow V, Reddel C, Pennings G, Scott E, Pasqualon T, e1001372, 2013 . PMID:23382654 AC, Desai R, Allan CM, Smith JT, Handelsman DJ and Ng AC, Yeoh T, Curnow J and Kritharides L Walters KA Global hypercoagulability in patients with schizophrenia Bermeo S, Vidal C, Zhou H, Duque G. Haplosufficient genomic androgen receptor signaling receiving long-term antipsychotic therapy . Schizophr Res Lamin A/C acts as an essential factor in mesenchymal is adequate to protect female mice from induction 162 (1-3): 175-182, 2015 . PMID:25634682 stem cell differentiation through the regulation of the of polycystic ovary syndrome features by prenatal dynamics of the Wnt/b-catenin pathway . J Cell Biochem hyperandrogenization . Endocrinology 156 (4): 1441- Chow V, Yeoh T, Ng AC, Pasqualon T, Scott E, Plater 2015 [Epub ahead of print] . 1452, 2015 . PMID:25643156 J, Whitwell B, Hanzek D, Chung T, Thomas L, Celermajer DS and Kritharides L Ben Freedman S, Gersh BJ and Lip GY Caldwell AS, Middleton LJ, Jimenez M, Desai R, Asymptomatic left ventricular dysfunction with Misperceptions of aspirin efficacy and safety may McMahon AC, Allan CM, Handelsman DJ and Walters long-term clozapine treatment for schizophrenia: a perpetuate anticoagulant underutilization in atrial KA multicentre cross-sectional cohort study . Open Heart 1 fibrillation . Eur Heart J 36 (11): 653-656, 2015 . Characterization of reproductive, metabolic, and (1): e000030, 2014 . PMID:25332789 PMID:25548061 endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models . Endocrinology Clark TR, Freedman SB, Croft AJ, Dalton HE, Bing R, Naoum C and Kritharides L 155 (8): 3146-3159, 2014 . PMID:24877633 Luscombe GM, Brown AM, Tiller DJ and Frommer The vulnerable right ventricle: recurrent, transient right MS ventricular failure on a background of systemic sclerosis Chaudhry R, Kidambi A, Brewer MH, Antonellis A, Medical graduates becoming rural doctors: rural and previous anthracycline exposure . Int J Cardiol 178 Mathews K, Nicholson G and Kennerson M background versus extended rural placement . Med J 223-225, 2015 . PMID:25464259 Re-analysis of an original CMTX3 family using exome Aust 199 (11): 779-782, 2013 . PMID:24329657 sequencing identifies a known BSCL2 mutation . Muscle Birzniece V, Umpleby MA, Poljak A, Handelsman DJ Nerve 47 (6): 922-924, 2013 . PMID:23553728 Cogger VC, Mitchell SJ, Warren A, de Cabo R and Le and Ho KK Couteur DG Oral low-dose testosterone administration induces Cheng XB, Jimenez M, Desai R, Middleton LJ, Joseph Age-related loss of responsiveness to 2,5-dimethoxy-4- whole-body protein anabolism in postmenopausal SR, Ning G, Allan CM, Smith JT, Handelsman DJ and iodoamphetamine in liver sinusoidal endothelial cells . women: a novel liver-targeted therapy . Eur J Endocrinol Walters KA J Gerontol A Biol Sci Med Sci 69 (5): 514-518, 2014 . 169 (3): 321-327, 2013 . PMID:23832866 Characterizing the neuroendocrine and ovarian defects PMID:23974079 of androgen receptor-knockout female mice . Am J Bleicher K, Cumming RG, Naganathan V, Blyth FM, Physiol Endocrinol Metab 305 (6): E717-726, 2013 . Cogger VC, Mitchell SJ, Warren A, de Cabo R and Le Le Couteur DG, Handelsman DJ, Waite LM and Seibel PMID:23880317 Couteur DG MJ Age-related loss of responsiveness to 2,5-dimethoxy-4- U-shaped association between serum 25-hydroxyvitamin Chesi A, Staahl BT, Jovicic A, Couthouis J, Fasolino iodoamphetamine in liver sinusoidal endothelial cells . D and fracture risk in older men: results from the M, Raphael AR, Yamazaki T, Elias L, Polak M, Kelly C, J Gerontol A Biol Sci Med Sci 69 (5): 514-518, 2014 . prospective population-based CHAMP study . J Bone Williams KL, Fifita JA, Maragakis NJ, Nicholson GA, PMID:23974079 Miner Res 29 (9): 2024-2031, 2014 . PMID:24677358 King OD, Reed R, Crabtree GR, Blair IP, Glass JD and Gitler AD Cogger VC, Roessner U, Warren A, Fraser R and Le Bleicher K, Cumming RG, Naganathan V, Seibel MJ, Exome sequencing to identify de novo mutations in Couteur DG Blyth FM, Le Couteur DG, Handelsman DJ, Creasey sporadic ALS trios . Nat Neurosci 16 (7): 851-855, 2013 . A Sieve-Raft Hypothesis for the regulation of endothelial HM and Waite LM PMID:23708140 fenestrations . Comput Struct Biotechnol J 8 Predictors of the rate of BMD loss in older men: findings e201308003, 2013 . PMID:24688743 from the CHAMP study . Osteoporos Int 24 (7): 1951- Cheung W, Clayton N, Li F, Tan J, Milliss D, 1963, 2013 . PMID:23212282 Thanakrishnan G and Maitz P Cogger VC, Svistounov D, Warren A, Zykova S, Melvin The effect of endotracheal tube size on voice and RG, Solon-Biet SM, O’Reilly JN, McMahon AC, Ballard Brock KE, Ke L, Tseng M, Clemson L, Koo FK, Jang H, swallowing function in patients with thermal burn injury: JW, De Cabo R, Le Couteur DG and Lebel M Seibel MJ, Mpofu E, Fraser DR and Mason RS an evaluation using the Australian Therapy Outcome Liver aging and pseudocapillarization in a Werner Vitamin D status is associated with sun exposure, vitamin Measures (AusTOMS) . Int J Speech Lang Pathol 15 (2): syndrome mouse model . J Gerontol A Biol Sci Med Sci D and calcium intake, acculturation and attitudes in 216-220, 2013 . PMID:22998722 69 (9): 1076-1086, 2014 . PMID:24149428 immigrant East Asian women living in Sydney . J Steroid Biochem Mol Biol 136 214-217, 2013 . PMID:23262263 Choi J, Psarommatis B, Gao YR, Zheng Y, Handelsman Cooper MS DJ and Simanainen U Role of endocrine dysfunction in frequently unexplained The role of androgens in experimental rodent mammary disorders . Eur J Pain 18 (3): 299-300, 2014 .

Biennial Report 2013-15 31 PMID:25728516 Older People After Hospitalization . J Am Med Dir Assoc people: prescribing patterns according to pain prevalence 2015 . PMID:25703448 and adherence to clinical guidelines . Pain 155 (9): 1814- Cooper TG and Handelsman DJ 1820, 2014 . PMID:24954164 Falling sperm counts and global oestrogenic pollution: Favaloro J, Brown R, Aklilu E, Yang S, Suen H, Hart postscript . Asian J Androl 15 (2): 208-211, 2013 . D, Fromm P, Gibson J, Khoo L, Ho PJ and Joshua D Gnjidic D, Hilmer SN and Le Couteur DG PMID:23416896 Myeloma skews regulatory T and pro-inflammatory T Optimal cutoff of polypharmacy and outcomes - reply . J helper 17 cell balance in favor of a suppressive state . Leuk Clin Epidemiol 66 (4): 465-466, 2013 . PMID:23337784 Cooper MC, Seibel MJ, Zhou H Lymphoma 55 (5): 1090-1098, 2014 . PMID:23865833 Glucocorticoids, bone and energy metabolism . Bone Gnjidic D, Le Couteur DG, Blyth FM, Travison T, Rogers 2015 [Epub ahead of print] . PMID 26051468 Favaloro J, Liyadipitiya T, Brown R, Yang S, Suen H, K, Naganathan V, Cumming RG, Waite L, Seibel MJ, Woodland N, Nassif N, Hart D, Fromm P, Weatherburn Handelsman DJ, McLachlan AJ and Hilmer SN Deif B, Lowres N and Freedman SB C, Gibson J, Ho PJ and Joshua D Statin use and clinical outcomes in older men: a Screening for atrial fibrillation above age 65 detects an Myeloid derived suppressor cells are numerically, prospective population-based study . BMJ Open 3 (3): asymptomatic subset at high risk of stroke . Int J Cardiol functionally and phenotypically different in patients with 2013 . PMID:23474793 164 (3): 371-372, 2013 . PMID:22964080 multiple myeloma . Leuk Lymphoma 55 (12): 2893-2900, 2014 . PMID:24625328 Gnjidic D, Le Couteur DG and Hilmer SN Ding D, Rogers K, Macniven R, Kamalesh V, Discontinuation of statins in routine care settings . Ann Kritharides L, Chalmers J and Bauman A Fifita JA, Williams KL, McCann EP, O’Brien A, Bauer Intern Med 159 (1): 73-74, 2013 . PMID:23817713 Revisiting lifestyle risk index assessment in a large DC, Nicholson GA and Blair IP Australian sample: should sedentary behavior and sleep Mutation analysis of MATR3 in Australian familial Gnjidic D, Le Couteur DG and Hilmer SN be included as additional risk factors? Prev Med 60 102- amyotrophic lateral sclerosis . Neurobiol Aging 36 (3): Discontinuing drug treatments . BMJ 349 g7013, 2014 . 106, 2014 . PMID:24380793 1602 e1601-1602, 2015 . PMID:25523636 PMID:25416561

Drew AP, Zhu D, Kidambi A, Ly C, Tey S, Brewer MH, Fransen M, Su S, Harmer A, Blyth FM, Naganathan V, Gnjidic D, Le Couteur DG, Hilmer SN, Cumming RG, Ahmad-Annuar A, Nicholson GA and Kennerson ML Sambrook P, Le Couteur D and Cumming RG Blyth FM, Naganathan V, Waite L, Handelsman DJ Improved inherited peripheral neuropathy genetic A longitudinal study of knee pain in older men: Concord and Bell JS diagnosis by whole-exome sequencing . Mol Genet Health and Ageing in Men Project . Age Ageing 43 (2): Sedative load and functional outcomes in community- Genomic Med 3 (2): 143-154, 2015 . PMID:25802885 206-212, 2014 . PMID:24317190 dwelling older Australian men: the CHAMP study . Fundam Clin Pharmacol 28 (1): 10-19, 2014 . PMID:22849300 Du XM, Kim MJ, Hou L, Le Goff W, Chapman MJ, Van Ganda K, Puech M, Chen JS, Speerin R, Bleasel J, Eck M, Curtiss LK, Burnett JR, Cartland SP, Quinn Center JR, Eisman JA, March L and Seibel MJ Gnjidic D, Le Couteur DG, Pearson SA, McLachlan AJ, CM, Kockx M, Kontush A, Rye KA, Kritharides L and Models of care for the secondary prevention of Viney R, Hilmer SN, Blyth FM, Joshy G and Banks E Jessup W osteoporotic fractures: a systematic review and High risk prescribing in older adults: prevalence, clinical HDL Particle Size Is a Critical Determinant of ABCA1- meta-analysis . Osteoporos Int 24 (2): 393-406, 2013 . and economic implications and potential for intervention Mediated Macrophage Cellular Cholesterol Export . Circ PMID:22829395 at the population level . BMC Public Health 13 115, 2013 . Res 116 (7): 1133-1142, 2015 . PMID:25589556 PMID:23388494 Ganda K, Schaffer A and Seibel MJ Duong TT, Chami B, McMahon AC, Fong GM, Dennis Predictors of re-fracture amongst patients managed Gnjidic D, Wilson N, March L, Cumming RG, Cameron JM, Freedman SB and Witting PK within a secondary fracture prevention program: a 7-year ID and Hilmer SN Pre-treatment with the synthetic antioxidant T-butyl prospective study . Osteoporos Int 26 (2): 543-551, 2015 . Statin utilisation patterns in older Australians living in bisphenol protects cerebral tissues from experimental PMID:25189427 residential care: 1-year prevalence study . Intern Med J ischemia reperfusion injury . J Neurochem 130 (6): 733- 45 (1): 106-109, 2015 . PMID:25582939 747, 2014 . PMID:24766199 Ganda K and Seibel MJ Rapid biochemical response to denosumab in fibrous Goltsman D, Li Z, Bruce E, Darton A, Thornbury K, Durvasula S, Gies P, Mason RS, Chen JS, Henderson dysplasia of bone: report of two cases . Osteoporos Int 25 Maitz PK and Kennedy P S, Seibel MJ, Sambrook PN, March LM, Lord SR, Kok (2): 777-782, 2014 . PMID:24311113 Too hot to handle? Hot water bottle injuries in Sydney, C, Macara M, Parmenter TR and Cameron ID Australia . Burns 41 (4): 770-777, 2015 . PMID:25540882 Vitamin D response of older people in residential aged Gao YR, Walters KA, Desai R, Zhou H, Handelsman care to sunlight-derived ultraviolet radiation . Arch DJ and Simanainen U Goltsman D, Li Z, Bruce E and Maitz PK Osteoporos 9 (1): 197, 2014 . PMID:25311734 Androgen receptor inactivation resulted in acceleration Geospatial and epidemiological analysis of severe burns in pubertal mammary gland growth, upregulation of in New South Wales by residential postcodes . Burns 40 Edelman JJ, Fung YL, Pennings GJ, Reddel CJ, ERalpha expression, and Wnt/beta-catenin signaling in (4): 670-682, 2014 . PMID:24290854 Bannon PG, Bayfield MS, Kritharides L, Fraser JF female mice . Endocrinology 155 (12): 4951-4963, 2014 . and Vallely MP PMID:25076121 Hairi NN, Cumming RG, Blyth FM and Naganathan V Off-pump coronary artery bypass surgery induces Chronic pain, impact of pain and pain severity with physical prolonged alterations to host neutrophil physiology . Gasiorowski RE, Clark GJ, Bradstock K and Hart DN disability in older people--is there a gender difference? Shock 39 (2): 149-154, 2013 . PMID:23324884 Antibody therapy for acute myeloid leukaemia . Br J Maturitas 74 (1): 68-73, 2013 . PMID:23103063 Haematol 164 (4): 481-495, 2014 . PMID:24321020 Edelman JJ, Reddel CJ, Kritharides L, Bannon PG, Handelsman DJ Fraser JF, Curnow JL and Vallely MP Gasiorowski RE, Ju X, Hart DN and Clark GJ Global trends in testosterone prescribing, 2000-2011: Natural history of hypercoagulability in patients CD300 molecule regulation of human dendritic cell expanding the spectrum of prescription drug misuse . undergoing coronary revascularization and effect of functions . Immunol Lett 149 (1-2): 93-100, 2013 . Med J Aust 199 (8): 548-551, 2013 . PMID:24138381 preoperative myocardial infarction . J Thorac Cardiovasc PMID:23072861 Surg 148 (2): 536-543, 2014 . PMID:24280714 Handelsman DJ Geevasinga N, Menon P, Howells J, Nicholson GA, Mechanisms of action of testosterone--unraveling a Edelman JJ, Reddel CJ, Kritharides L, Bannon PG, Kiernan MC and Vucic S Gordian knot . N Engl J Med 369 (11): 1058-1059, 2013 . Fraser JF, Curnow JL and Vallely MP Axonal ion channel dysfunction in c9orf72 familial PMID:24024843 Natural history of hypercoagulability in patients amyotrophic lateral sclerosis . JAMA Neurol 72 (1): 49- undergoing coronary revascularization and effect of 57, 2015 . PMID:25384182 Handelsman DJ preoperative myocardial infarction . J Thorac Cardiovasc Mendelian randomization: loosening the Gordian knot Surg 148 (2): 536-543, 2014 . PMID:24280714 George R, Merten S, Wang TT, Kennedy P and Maitz P of testosterone and male ageing . Asian J Androl 15 (5): In vivo analysis of dermal and systemic absorption of silver 579-581, 2013 . PMID:23770937 Fairhall N, Sherrington C, Cameron ID, Blyth F, nanoparticles through healthy human skin . Australas J Naganathan V, Clemson L, Le Couteur D, Handelsman Dermatol 55 (3): 185-190, 2014 . PMID:24004310 Handelsman DJ and Cooper TG DJ, Waite L and Cumming RG Falling sperm counts and global estrogenic pollution: Predicting participation restriction in community- Girgis CM, Kuo I and Handelsman DJ what have we learned over 20 years? Asian J Androl 15 dwelling older men: the Concord Health and Ageing Acute hepatitis and fevers in an amateur body-builder: a (2): 159-161, 2013 . PMID:23416895 in Men Project . Age Ageing 43 (1): 31-37, 2014 . new complication of synthetic androgen abuse? Endocr PMID:23927887 Pract 20 (8): e130-133, 2014 . PMID:24641932 Handelsman DJ, Idan A, Grainger J, Goebel C, Turner L and Conway AJ Farag I, Howard K, Hayes AJ, Ferreira ML, Lord Gnjidic D, Blyth FM, Le Couteur DG, Cumming RG, Detection and effects on serum and urine steroid and SR, Close JT, Vogler C, Dean CM, Cumming RG and McLachlan AJ, Handelsman DJ, Seibel M, Waite L LH of repeated GnRH analog (leuprolide) stimulation . Sherrington C and Naganathan V J Steroid Biochem Mol Biol 141 113-120, 2014 . Cost-effectiveness of a Home-Exercise Program Among Nonsteroidal anti-inflammatory drugs (NSAIDs) in older PMID:24495617

32 Biennial Report 2013-15 Handelsman DJ, Jimenez M, Singh GK, Spaliviero J, Hirani V, Blyth F, Naganathan V, Le Couteur DG, Seibel study and meta-analysis . PLoS One 8 (11): e82305, 2013 . Desai R and Walters KA MJ, Waite LM, Handelsman DJ and Cumming RG PMID:24282622 Measurement of testosterone by immunoassays and Sarcopenia Is Associated With Incident Disability, mass spectrometry in mouse serum, testicular, and Institutionalization, and Mortality in Community- Hosseini SR, Cumming RG, Kheirkhah F, Nooreddini ovarian extracts . Endocrinology 156 (1): 400-405, 2015 . Dwelling Older Men: The Concord Health and Ageing in H, Baiani M, Mikaniki E, Taghipour-darzi M, Akhavan PMID:25365769 Men Project . J Am Med Dir Assoc 2015 . PMID:25820131 Niaki H, Rasolinejad SA, Mostafazadeh A, Parsian H and Bijani A Handelsman DJ, Newman JD, Jimenez M, McLachlan Hirani V, Blyth FM, Naganathan V, Cumming RG, Le Cohort profile: the Amirkola Health and Ageing Project R, Sartorius G and Jones GR Couteur DG, Handelsman DJ, Waite LM and Seibel (AHAP) . Int J Epidemiol 43 (5): 1393-1400, 2014 . Performance of direct estradiol immunoassays with MJ PMID:23918798 human male serum samples . Clin Chem 60 (3): 510-517, Active vitamin D (1,25 dihydroxyvitamin D) is associated 2014 . PMID:24334824 with chronic pain in older Australian men: the Concord Hsieh V, Kim MJ, Gelissen IC, Brown AJ, Sandoval Health and Ageing in Men Project . J Gerontol A Biol Sci C, Hallab JC, Kockx M, Traini M, Jessup W and Handelsman DJ, Sivananathan T, Andres L, Bathur F, Med Sci 70 (3): 387-395, 2015 . PMID:25104821 Kritharides L Jayadev V and Conway AJ Cellular cholesterol regulates ubiquitination and Randomised controlled trial of whether erotic material Hirani V, Cumming RG, Blyth F, Naganathan V, Le degradation of the cholesterol export proteins ABCA1 is required for semen collection: impact of informed Couteur DG, Waite LM, Handelsman DJ and Seibel and ABCG1 . J Biol Chem 289 (11): 7524-7536, 2014 . consent on outcome . Andrology 1 (6): 943-947, 2013 . MJ PMID:24500716 PMID:24124176 Cross-sectional and longitudinal associations between the active vitamin D metabolite (1,25 dihydroxyvitamin Hsu B, Cumming RG, Blyth FM, Naganathan V, Le Handelsman DJ and Wartofsky L D) and haemoglobin levels in older Australian men: the Couteur DG, Seibel MJ, Waite LM and Handelsman Requirement for mass spectrometry sex steroid assays Concord Health and Ageing in Men Project . Age (Dordr) DJ in the Journal of Clinical Endocrinology and Metabolism . 37 (1): 9749, 2015 . PMID:25649710 Longitudinal and cross-sectional relationships of J Clin Endocrinol Metab 98 (10): 3971-3973, 2013 . circulating reproductive hormone levels to self-rated PMID:24098015 Hirani V, Cumming RG, Blyth FM, Naganathan V, Le health and health-related quality of life in community- Couteur DG, Handelsman DJ, Waite LM and Seibel dwelling older men . J Clin Endocrinol Metab 99 (5): Hardy MY, Vari F, Rossetti T, Hart DN and Prue RL MJ 1638-1647, 2014 . PMID:24552220 A flow cytometry based assay for the enumeration of Vitamin D status among older community dwelling men regulatory T cells in whole blood . J Immunol Methods living in a sunny country and associations with lifestyle Hsu B, Cumming RG, Blyth FM, Naganathan V, Le 390 (1-2): 121-126, 2013 . PMID:22824721 factors: the Concord Health and Ageing in Men Project, Couteur DG, Seibel MJ, Waite LM and Handelsman Sydney, Australia . J Nutr Health Aging 17 (7): 587-593, DJ Hardy RS, Hulso C, Liu Y, Gasparini SJ, Fong-Yee 2013 . PMID:23933868 Longitudinal and cross-sectional relationships of C, Tu J, Stoner S, Stewart PM, Raza K, Cooper MS, circulating reproductive hormone levels to self-rated Seibel MJ and Zhou H Hirani V, Cumming RG, Le Couteur DG, Naganathan health and health-related quality of life in community- Characterisation of fibroblast-like synoviocytes from a V, Blyth F, Handelsman DJ, Waite LM and Seibel MJ dwelling older men . J Clin Endocrinol Metab 99 (5): murine model of joint inflammation . Arthritis Res Ther Low levels of 25-hydroxy vitamin D and active 1638-1647, 2014 . PMID:24552220 15 (1): R24, 2013 . PMID:23363614 1,25-dihydroxyvitamin D independently associated with type 2 diabetes mellitus in older Australian men: the Hsu B, Cumming RG, Blyth FM, Naganathan V, Le Hardy RS, Seibel MJ and Cooper MS Concord Health and Ageing in Men Project . J Am Geriatr Couteur DG, Seibel MJ, Waite LM and Handelsman Targeting 11beta-hydroxysteroid dehydrogenases: a Soc 62 (9): 1741-1747, 2014 . PMID:25112415 DJ novel approach to manipulating local glucocorticoid The longitudinal relationship of sexual function and levels with implications for rheumatic disease . Curr Opin Hirani V, Cumming RG, Naganathan V, Blyth F, Le androgen status in older men: the concord health and Pharmacol 13 (3): 440-444, 2013 . PMID:23540586 Couteur DG, Handelsman DJ, Waite LM and Seibel ageing in men project . J Clin Endocrinol Metab 100 (4): MJ 1350-1358, 2015 . PMID:25629357 Harish V and Maitz PK Associations between serum 25-hydroxyvitamin D Uninterrupted continuous negative pressure wound concentrations and multiple health conditions, physical Hsu B, Cumming RG, Naganathan V, Blyth FM, Le therapy is safe and can facilitate engraftment of dermal performance measures, disability, and all-cause Couteur DG, Seibel MJ, Waite LM and Handelsman regeneration templates . J Plast Reconstr Aesthet Surg mortality: the Concord Health and Ageing in Men Project . DJ 67 (7): 1011-1013, 2014 . PMID:24503327 J Am Geriatr Soc 62 (3): 417-425, 2014 . PMID:24576190 Associations between circulating reproductive hormones and SHBG and prevalent and incident metabolic syndrome Harish V, Raymond AP, Issler AC, Lajevardi SS, Hirani V, Naganathan V, Blyth F, Le Couteur DG, in community-dwelling older men: the Concord Health Chang LY, Maitz PK and Kennedy P Gnjidic D, Stanaway FF, Seibel MJ, Waite LM, and Ageing in Men Project . J Clin Endocrinol Metab 99 Response to Letter to the Editor: ‘burn surface area Handelsman DJ and Cumming RG (12): E2686-2691, 2014 . PMID:25259909 calculation instead of burn size estimation: our opinion’ . Multiple, but not traditional risk factors predict mortality Burns 40 (8): 1814, 2014 . PMID:25406890 in older people: the Concord Health and Ageing in Men Hsu B, Cumming RG, Naganathan V, Blyth FM, Le Project . Age (Dordr) 36 (6): 9732, 2014 . PMID:25403157 Couteur DG, Seibel MJ, Waite LM and Handelsman Harish V, Raymond AP, Issler AC, Lajevardi SS, DJ Chang LY, Maitz PK and Kennedy P Hirani V, Naganathan V, Blyth F, Le Couteur DG, Kelly Longitudinal relationships of circulating reproductive Accuracy of burn size estimation in patients transferred P, Handelsman DJ, Waite LM and Cumming RG hormone with functional disability, muscle mass, and to adult Burn Units in Sydney, Australia: an audit of 698 Cross-Sectional and Longitudinal Associations Between strength in community-dwelling older men: the Concord patients . Burns 41 (1): 91-99, 2015 . PMID:24972983 Anemia and Frailty in Older Australian Men: The Concord Health and Ageing in Men project . J Clin Endocrinol Health and Aging in Men Project . J Am Med Dir Assoc Metab 99 (9): 3310-3318, 2014 . PMID:24628559 Harish V, Raymond AP and Maitz PK 2015 . PMID:25840760 Hsu B, Cumming RG, Seibel MJ, Naganathan V, Blyth Reconstruction of soft tissue necrosis secondary to FM, Bleicher K, Dave A, Le Couteur DG, Waite LM and cryoglobulinaemia . J Plast Reconstr Aesthet Surg 67 Hirani V, Naganathan V, Cumming RG, Blyth F, Le Handelsman DJ (8): 1151-1154, 2014 . PMID:24755034 Couteur DG, Handelsman DJ, Waite LM and Seibel MJ Reproductive Hormones and Longitudinal Change in Hazra R, Corcoran L, Robson M, McTavish KJ, Upton Associations between frailty and serum Bone Mineral Density and Incident Fracture Risk in Older D, Handelsman DJ and Allan CM 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D Men: The Concord Health and Ageing in Men Project . J Temporal role of Sertoli cell androgen receptor concentrations in older Australian men: the Concord Bone Miner Res 2015 . PMID:25736139 expression in spermatogenic development . Mol Health and Ageing in Men Project . J Gerontol A Biol Sci Hsu B, Cumming RG, Waite LM, Blyth FM, Naganathan Endocrinol 27 (1): 12-24, 2013 . PMID:23160479 Med Sci 68 (9): 1112-1121, 2013 . PMID:23657973 V, Le Couteur DG, Seibel MJ and Handelsman DJ Hazra R, Jimenez M, Desai R, Handelsman DJ and Holden CA, Collins VR, Handelsman DJ, Jolley D, Longitudinal Relationships between Reproductive Allan CM Pitts M and Men in Australia Telephone Survey Hormones and Cognitive Decline in Older Men: The Sertoli cell androgen receptor expression regulates Working G Concord Health and Ageing in Men Project . J Clin temporal fetal and adult Leydig cell differentiation, Healthy aging in a cross-sectional study of Australian Endocrinol Metab jc20151016, 2015 . PMID:25867811 function, and population size . Endocrinology 154 (9): men: what has sex got to do with it? Aging Male 17 (1): Huang X, Hancock DP, Gosby AK, McMahon AC, Solon 3410-3422, 2013 . PMID:23766127 25-29, 2014 . PMID:24491170 SM, Le Couteur DG, Conigrave AD, Raubenheimer D Hazra R, Upton D, Jimenez M, Desai R, Handelsman Holliday EG, Magee CA, Kritharides L, Banks E and and Simpson SJ DJ and Allan CM Attia J Effects of dietary protein to carbohydrate balance In vivo actions of the Sertoli cell glucocorticoid receptor . Short sleep duration is associated with risk of future on energy intake, fat storage, and heat production Endocrinology 155 (3): 1120-1130, 2014 . PMID:24424066 diabetes but not cardiovascular disease: a prospective in mice . Obesity (Silver Spring) 21 (1): 85-92, 2013 .

Biennial Report 2013-15 33 PMID:23404943 Keski-Rahkonen P, Huhtinen K, Desai R, Harwood DT, inappropriately urged despite absence of evidence . Am Handelsman DJ, Poutanen M and Auriola S Fam Physician 89 (11): 864-865, 2014 . PMID:25077389 Huhtinen K, Saloniemi-Heinonen T, Keski-Rahkonen LC-MS analysis of estradiol in human serum and P, Desai R, Laajala D, Stahle M, Hakkinen MR, endometrial tissue: Comparison of electrospray Le Couteur DG, Doust J, Creasey H and Brayne C Awosanya M, Suvitie P, Kujari H, Aittokallio T, ionization, atmospheric pressure chemical ionization and Political drive to screen for pre-dementia: not evidence Handelsman DJ, Auriola S, Perheentupa A and atmospheric pressure photoionization . J Mass Spectrom based and ignores the harms of diagnosis . BMJ 347 Poutanen M 48 (9): 1050-1058, 2013 . PMID:24078246 f5125, 2013 . PMID:24018000 Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the King LK, Henneicke H, Seibel MJ, March L and Le Couteur DG, Simpson SJ and de Cabo R endometrium and endometriosis lesions . J Clin Anandacoomarasmy A Are glycans the Holy Grail for biomarkers of aging? Endocrinol Metab 99 (11): E2188-2197, 2014 . Association of adipokines and joint biomarkers with J Gerontol A Biol Sci Med Sci 69 (7): 777-778, 2014 . PMID:25137424 cartilage-modifying effects of weight loss in obese PMID:24325897 subjects . Osteoarthritis Cartilage 23 (3): 397-404, 2015 . Huizer-Pajkos A, Kane AE, Howlett SE, Mach J, PMID:25481288 Le Couteur DG, Tay SS, Solon-Biet S, Bertolino P, Mitchell SJ, de Cabo R, Le Couteur DG and Hilmer SN McMahon AC, Cogger VC, Colakoglu F, Warren A, Adverse Geriatric Outcomes Secondary to Polypharmacy Kockx M, Jessup W and Kritharides L Holmes AJ, Pichaud N, Horan M, Correa C, Melvin RG, in a Mouse Model: The Influence of Aging . J Gerontol A Getting to the ‘guts’ of the matter: intestinal control of Turner N, Ballard JW, Ruohonen K, Raubenheimer D Biol Sci Med Sci 2015 . PMID:25940962 lipid metabolism . Curr Opin Lipidol 24 (1): 105-106, and Simpson SJ 2013 . PMID:23298966 The Influence of Macronutrients on Splanchnic and Ilomaki J, Gnjidic D, Hilmer SN, Le Couteur DG, Hepatic Lymphocytes in Aging Mice . J Gerontol A Biol Naganathan V, Cumming RG, Waite LM, Seibel MJ, Kockx M, Karunakaran D, Traini M, Xue J, Huang Sci Med Sci 2014 . PMID:25335766 Blyth FM, Handelsman DJ and Bell JS KY, Nawara D, Gaus K, Jessup W, Robinson PJ and Psychotropic drug use and alcohol drinking in community- Kritharides L Le Couteur DG, Wilder SM, de Cabo R and Simpson dwelling older Australian men: the CHAMP study . Drug Pharmacological inhibition of dynamin II reduces SJ Alcohol Rev 32 (2): 218-222, 2013 . PMID:22882728 constitutive protein secretion from primary human The evolution of research on ageing and nutrition . macrophages . PLoS One 9 (10): e111186, 2014 . J Gerontol A Biol Sci Med Sci 69 (1): 1-2, 2014 . Ilomaki J, Gnjidic D, Le Couteur DG, Bell JS, Blyth PMID:25347775 PMID:24022588 FM, Handelsman DJ, Cumming RG, Seibel MJ, Waite LM, Naganathan V and Hilmer SN Kong X, Yu J, Bi J, Qi H, Di W, Wu L, Wang L, Zha J, Lv Le TY, Ashton AW, Mardini M, Stanton PG, Funder JW, Alcohol consumption and tobacco smoking among S, Zhang F, Li Y, Hu F, Liu F, Zhou H, Liu J, and Ding G Handelsman DJ and Mihailidou AS community-dwelling older Australian men: the Concord Glucocorticoids Transcriptionally Regulate miR-27b Role of androgens in sex differences in cardiac damage Health and Ageing in Men Project . Australas J Ageing 33 Expression Promoting Body Fat Accumulation Via during myocardial infarction . Endocrinology 155 (2): (3): 185-192, 2014 . PMID:24521471 Suppressing the Browning of White Adipose Tissue . 568-575, 2014 . PMID:24424037 Diabetes 2015;64:393–404 . PMID:25187367 Ireland AW, Kelly PJ and Cumming RG Lecce L, Lam YT, Lindsay LA, Yuen SC, Simpson PJ, Risk factor profiles for early and delayed mortality after Kouladjian L, Hilmer SN, Chen TF, Le Couteur DG and Handelsman DJ and Ng MK hip fracture: Analyses of linked Australian Department of Gnjidic D Aging impairs VEGF-mediated, androgen-dependent Veterans’ Affairs databases . Injury 2015 . PMID:25813734 Assessing the harms of polypharmacy requires careful regulation of angiogenesis . Mol Endocrinol 28 (9): 1487- interpretation and consistent definitions . Br J Clin 1501, 2014 . PMID:25058601 Ireland AW, Kelly PJ and Cumming RG Pharmacol 78 (3): 670-671, 2014 . PMID:25279408 Total hospital stay for hip fracture: measuring the Li A, Hardy R, Stoner S, Tuckermann J, Seibel M and variations due to pre-fracture residence, rehabilitation, Kozan P, Chalasani S, Handelsman DJ, Pike AH and Zhou H complications and comorbidities . BMC Health Serv Res Crawford BA Deletion of mesenchymal glucocorticoid receptor 15 17, 2015 . PMID:25609030 A Leydig cell tumor of the ovary resulting in extreme attenuates embryonic lung development and hyperandrogenism, erythrocytosis, and recurrent abdominal wall closure . PLoS One 8 (5): e63578, 2013 . Jang H, Koo FK, Ke L, Clemson L, Cant R, Fraser DR, pulmonary embolism . J Clin Endocrinol Metab 99 (1): PMID:23696835 Seibel MJ, Tseng M, Mpofu E, Mason RS and Brock K 12-17, 2014 . PMID:24152686 Culture and sun exposure in immigrant East Asian Liang C, Howells J, Kennerson M, Nicholson GA, women living in Australia . Women Health 53 (5): 504- Kritharides L Burke D and Ng K 518, 2013 . PMID:23879460 Not so “good” cholesterol . BMJ 349 g4664, 2014 . Axonal excitability in X-linked dominant Charcot Marie PMID:25038076 Tooth disease . Clin Neurophysiol 125 (6): 1261-1269, Javadzadegan A, Yong AS, Chang M, Ng AC, 2014 . PMID:24290847 Yiannikas J, Ng MK, Behnia M and Kritharides L Kritharides L and Lowe HC Flow recirculation zone length and shear rate are Extracting the ESSENCE - cardiovascular health for Liang X, Grice JE, Zhu Y, Liu D, Sanchez WY, Li Z, differentially affected by stenosis severity in human Aboriginal and Torres Strait Islander Australians . Heart Crawford DH, Le Couteur DG, Cogger VC, Liu X, Xu ZP coronary arteries . Am J Physiol Heart Circ Physiol 304 Lung Circ 24 (2): 107-109, 2015 . PMID:25626637 and Roberts MS (4): H559-566, 2013 . PMID:23241317 Intravital multiphoton imaging of the selective uptake Landoure G, Zhu PP, Lourenco CM, Johnson JO, Toro of water-dispersible quantum dots into sinusoidal liver Jeremy RW, Kritharides L and Brown A C, Bricceno KV, Rinaldi C, Meilleur KG, Sangare M, cells . Small 11 (14): 1711-1720, 2015 . PMID:25504510 Improving outcomes after coronary artery bypass Diallo O, Pierson TM, Ishiura H, Tsuji S, Hein N, Fink surgery: lessons from indigenous Australians . Heart JK, Stoll M, Nicholson G, Gonzalez MA, Speziani F, Loh DA, Hairi NN, Choo WY, Mohd Hairi F, Peramalah Lung Circ 22 (8): 597-598, 2013 . PMID:23931682 Durr A, Stevanin G, Biesecker LG, Center NIHIS, D, Kandiben S, Lee PL, Gani N, Madzlan MF, Abd Accardi J, Landis DM, Gahl WA, Traynor BJ, Marques Hamid MA, Akram Z, Chu AS, Bulgiba A and Kanthan GL, Mitchell P, Rochtchina E, Cumming RG W, Jr., Zuchner S, Blackstone C, Fischbeck KH and Cumming RG and Wang JJ Burnett BG MultiComponent Exercise and theRApeutic lifeStyle Myopia and the long-term incidence of cataract and Hereditary spastic paraplegia type 43 (SPG43) is caused (CERgAS) intervention to improve physical performance cataract surgery: the Blue Mountains Eye Study . by mutation in C19orf12 . Hum Mutat 34 (10): 1357-1360, and maintain independent living among urban poor older Clin Experiment Ophthalmol 42 (4): 347-353, 2014 . 2013 . PMID:23857908 people - a cluster randomised controlled trial . BMC PMID:24024555 Geriatr 15 8, 2015 . PMID:25887235 Lau JK, Lowres N, Neubeck L, Brieger DB, Sy RW, Karunakaran D, Kockx M, Owen DM, Burnett JR, Galloway CD, Albert DE and Freedman SB Loheswaran G, Kapadia M, Gladman M, Pulapaka S, Jessup W and Kritharides L iPhone ECG application for community screening to Xu L, Stanojcic M and Sakic B Protein kinase C controls vesicular transport and detect silent atrial fibrillation: a novel technology to Altered neuroendocrine status at the onset of CNS secretion of apolipoprotein E from primary human prevent stroke . Int J Cardiol 165 (1): 193-194, 2013 . lupus-like disease . Brain Behav Immun 32 86-93, 2013 . macrophages . J Biol Chem 288 (7): 5186-5197, 2013 . PMID:23465249 PMID:23466502 PMID:23288845 Lau JK, Sy RW, Corbett A and Kritharides L Lowres N, Freedman SB, Gallagher R, Kirkness A, Kennerson ML, Yiu EM, Chuang DT, Kidambi A, Tso Myotonic dystrophy and the heart: A systematic review Marshman D, Orchard J and Neubeck L SC, Ly C, Chaudhry R, Drew AP, Rance G, Delatycki of evaluation and management . Int J Cardiol 184 600- Identifying postoperative atrial fibrillation in cardiac MB, Zuchner S, Ryan MM and Nicholson GA 608, 2015 . PMID:25769007 surgical patients posthospital discharge, using iPhone A new locus for X-linked dominant Charcot-Marie-Tooth ECG: a study protocol . BMJ Open 5 (1): e006849, 2015 . disease (CMTX6) is caused by mutations in the pyruvate Le Couteur DG and Brayne C PMID:25586373 dehydrogenase kinase isoenzyme 3 (PDK3) gene . Hum Should family physicians routinely screen patients Mol Genet 22 (7): 1404-1416, 2013 . PMID:23297365 for cognitive impairment? No: screening has been Lowres N, Neubeck L, Redfern J and Freedman SB

34 Biennial Report 2013-15 Screening to identify unknown atrial fibrillation . A Merom D, Stanaway FF, Handelsman DJ, Waite LM, (2): 464-469, 2015 . PMID:24385202 systematic review . Thromb Haemost 110 (2): 213-222, Seibel MJ, Blyth FM, Naganathan V and Cumming RG 2013 . PMID:23595785 Swimming and other sporting activities and the rate of Naoum C, Kritharides L, Ing A, Falk GL and Yiannikas falls in older men: longitudinal findings from the Concord J Lowres N, Neubeck L, Salkeld G, Krass I, McLachlan Health and Ageing in Men Project . Am J Epidemiol 180 Changes in lung volumes and gas-trapping in AJ, Redfern J, Bennett AA, Briffa T, Bauman A, (8): 830-837, 2014 . PMID:25193746 patients with large hiatal hernia . Clin Respir J 2015 . Martinez C, Wallenhorst C, Lau JK, Brieger DB, Sy PMID:25919863 RW and Freedman SB Mhaka-Mutepfa M, Cumming R and Mpofu E Naoum C, Kritharides L, Thomas L, Ng AC, Ridley L, Falk Feasibility and cost-effectiveness of stroke prevention Grandparents fostering orphans: influences of protective GL and Yiannikas J through community screening for atrial fibrillation factors on their health and well-being . Health Care using iPhone ECG in pharmacies . The SEARCH-AF Women Int 35 (7-9): 1022-1039, 2014 . PMID:24820960 Modulation of phasic left atrial function and left study . Thromb Haemost 111 (6): 1167-1176, 2014 . ventricular filling in patients with extrinsic left atrial PMID:24687081 Mhaka-Mutepfa M, Mpofu E and Cumming R compression by hiatal hernia . Int J Cardiol 176 (3): 1176- Impact of protective factors on resilience of grandparent 1178, 2014 . PMID:25147068 Lowres N, Redfern J, Freedman SB, Orchard J, carers fostering orphans and non-orphans in zimbabwe . 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J Gerontol A Biol Sci Mitsui J, Matsukawa T, Sasaki H, Yabe I, Matsushima The mobile revolution-using smartphone apps to Med Sci 69 (4): 387-397, 2014 . PMID:23863315 M, Durr A, Brice A, Takashima H, Kikuchi A, Aoki M, prevent cardiovascular disease . Nat Rev Cardiol 2015 . Ishiura H, Yasuda T, Date H, Ahsan B, Iwata A, Goto PMID:25801714 Mach J, Huizer-Pajkos A, Kane A, Jones B, McKenzie J, Ichikawa Y, Nakahara Y, Momose Y, Takahashi Y, C, Mitchell SJ, de Cabo R, Cogger VC, Le Couteur DG Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Neubeck L, Orchard J and Freedman SB and Hilmer SN Nishizawa M, Watanabe H, Ito M, Sobue G, Ishikawa Fog on the crystal ball? Missing atrial fibrillation in The effect of aging on mitochondrial and cytosolic K, Mizusawa H, Kanai K, Hattori T, Kuwabara S, forecasting the future of stroke . Stroke 44 (10): e136, hepatic intrinsic death pathway and apoptosis associated Arai K, Koyano S, Kuroiwa Y, Hasegawa K, Yuasa T, 2013 . PMID:24046011 proteins in Fischer 344 rats . Exp Gerontol 2015 . Yasui K, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, PMID:25910621 Kusunoki S, Osaki Y, Horiuchi M, Kondo T, Murayama Newman JD and Handelsman DJ S, Hattori N, Yamamoto M, Murata M, Satake W, Challenges to the measurement of oestradiol: comments Magee CA, Holliday EG, Attia J, Kritharides L and Toda T, Filla A, Klockgether T, Wullner U, Nicholson on an endocrine society position statement . Clin Biochem Banks E G, Gilman S, Tanner CM, Kukull WA, Stern MB, Lee Rev 35 (2): 75-79, 2014 . PMID:25210207 Investigation of the relationship between sleep duration, VM, Trojanowski JQ, Masliah E, Low PA, Sandroni P, all-cause mortality, and preexisting disease . Sleep Med Ozelius LJ, Foroud T and Tsuji S Ng AC, Chow V, Yong AS, Chung T and Kritharides L 14 (7): 591-596, 2013 . PMID:23517587 Variants associated with Gaucher disease in multiple Fluctuation of serum sodium and its impact on system atrophy . Ann Clin Transl Neurol 2 (4): 417-426, short and long-term mortality following acute Makovey J, Macara M, Chen JS, Hayward CS, March 2015 . PMID:25909086 pulmonary embolism . PLoS One 8 (4): e61966, 2013 . L, Seibel MJ and Sambrook PN PMID:23620796 Serum uric acid plays a protective role for bone loss in Mohan SS, Knuiman MW, Divitini ML, James AL, peri- and postmenopausal women: a longitudinal study . Musk AW, Handelsman DJ, Beilin J, Hunter M and Ng AC, Chow V, Yong AS, Chung T and Kritharides L Bone 52 (1): 400-406, 2013 . PMID:23111314 Yeap BB Prognostic impact of the Charlson comorbidity index Higher serum testosterone and dihydrotestosterone, on mortality following acute pulmonary embolism . Martinez C, Katholing A and Freedman SB but not oestradiol, are independently associated with Respiration 85 (5): 408-416, 2013 . PMID:23147354 Adverse prognosis of incidentally detected ambulatory favourable indices of lung function in community-dwelling atrial fibrillation . 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ANZ J Surg 2014 . and Lord SR The relationship between solar UV exposure, serum PMID:25040596 Can social dancing prevent falls in older adults? a vitamin D levels and serum prostate-specific antigen protocol of the Dance, Aging, Cognition, Economics levels, in men from New South Wales, Australia: the Nguyen TN, Hilmer SN and Cumming RG (DAnCE) fall prevention randomised controlled trial . CHAMP study . World J Urol 32 (5): 1251-1257, 2014 . Review of epidemiology and management of atrial BMC Public Health 13 477, 2013 . PMID:23675705 PMID:24190367 fibrillation in developing countries . Int J Cardiol 167 (6): 2412-2420, 2013 . 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PMID:25798731 Diekstra FP, Lauria G, Duga S, Corti S, Cereda C, PMID:25923961 Corrado L, Soraru G, Morrison KE, Williams KL, Scott IA and Le Couteur DG Nicholson GA, Blair IP, Dion PA, Leblond CS, Rouleau Prue RL, Vari F, Radford KJ, Tong H, Hardy MY, Physicians need to take the lead in deprescribing . Intern GA, Hardiman O, Veldink JH, van den Berg LH, Al- D’Rozario R, Waterhouse NJ, Rossetti T, Coleman R, Med J 45 (3): 352-356, 2015 . PMID:25735580 Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Tracey C, Goossen H, Gounder V, Crosbie G, Hancock Taroni F, Garcia-Redondo A, Wu Z, Glass JD, Gellera S, Diaz-Guilas S, Mainwaring P, Swindle P and Hart Seibel MJ, Cooper MS and Zhou H C, Ratti A, Brown RH, Jr., Silani V, Shaw CE and DN Glucocorticoid-induced osteoporosis: mechanisms, Landers JE A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells management, and future perspectives . Lancet Diabetes Exome-wide rare variant analysis identifies TUBA4A pulsed with HLA-A*0201 peptides for immunotherapy Endocrinol 1 (1): 59-70, 2013 . PMID:24622268 mutations associated with familial ALS . Neuron 84 (2): of metastatic hormone refractory prostate cancer . J 324-331, 2014 . PMID:25374358 Immunother 38 (2): 71-76, 2015 . PMID:25658616 Semeere AS, Lwanga I, Sempa J, Parikh S, Nakasujja N, Cumming R, Kambugu A and Mayanja-Kizza H Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen Purves-Tyson TD, Boerrigter D, Allen K, Zavitsanou Mortality and immunological recovery among older K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud K, Karl T, Djunaidi V, Double KL, Desai R, Handelsman adults on antiretroviral therapy at a large urban HIV clinic N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney DJ and Weickert CS in Kampala, Uganda . J Acquir Immune Defic Syndr 67 GJ, Sinclair DA, Raubenheimer D, Le Couteur DG and Testosterone attenuates and the selective estrogen (4): 382-389, 2014 . PMID:25171733 Simpson SJ receptor modulator, raloxifene, potentiates The ratio of macronutrients, not caloric intake, dictates amphetamine-induced locomotion in male rats . Horm Shahin K, Sartor M, Hart DN and Bradstock KF cardiometabolic health, aging, and longevity in ad Behav 70 73-84, 2015 . PMID:25747465 Alterations in chemokine receptor CCR5 expression on libitum-fed mice . Cell Metab 19 (3): 418-430, 2014 . blood dendritic cells correlate with acute graft-versus- PMID:24606899 Purves-Tyson TD, Owens SJ, Double KL, Desai R, host disease . Transplantation 96 (8): 753-762, 2013 . Handelsman DJ and Weickert CS PMID:23903010 Solon-Biet SM, Walters KA, Simanainen UK, McMahon Testosterone induces molecular changes in dopamine AC, Ruohonen K, Ballard JW, Raubenheimer D, signaling pathway molecules in the adolescent male rat Sherrington C, Lord SR, Vogler CM, Close JC, Howard Handelsman DJ, Le Couteur DG and Simpson SJ nigrostriatal pathway . PLoS One 9 (3): e91151, 2014 . K, Dean CM, Heller GZ, Clemson L, O’Rourke SD, Macronutrient balance, reproductive function, and PMID:24618531 Ramsay E, Barraclough E, Herbert RD and Cumming lifespan in aging mice . Proc Natl Acad Sci U S A 112 (11): RG 3481-3486, 2015 . PMID:25733862 Radford K, Mack HA, Draper B, Chalkley S, Daylight A post-hospital home exercise program improved G, Cumming R, Bennett H, Delbaere K and Broe GA mobility but increased falls in older people: a randomised Spies CM, Wiebe E, Tu J, Li A, Gaber T, Huscher D, Prevalence of dementia in urban and regional Aboriginal controlled trial . PLoS One 9 (9): e104412, 2014 . Seibel MJ, Zhou H and Buttgereit F Australians . Alzheimers Dement 11 (3): 271-279, 2015 . PMID:25180702 Acute murine antigen-induced arthritis is not affected by PMID:24985534 disruption of osteoblastic glucocorticoid signalling . BMC Simanainen U, Gao YR, Desai R, Jimenez M, Musculoskelet Disord 15 31, 2014 . PMID:24491163 Radford K, Mack HA, Draper B, Chalkley S, Delbaere Spaliviero J, Keast JR and Handelsman DJ K, Daylight G, Cumming RG, Bennett H and Broe GA Evidence for increased tissue androgen sensitivity in Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Comparison of Three Cognitive Screening Tools in neurturin knockout mice . J Endocrinol 218 (2): 151-163, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Older Urban and Regional Aboriginal Australians . 2013 . PMID:23678134 Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa Dement Geriatr Cogn Disord 40 (1-2): 22-32, 2015 . T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, PMID:25896073 Simanainen U, Ryan T, Li D, Suarez FG, Gao YR, Kimura F, Murayama S, Onodera O, Nishizawa M, Watson G, Wang Y and Handelsman DJ Yoshida M, Atsuta N, Sobue G, JaCals, Fifita JA, Radford K, Mack HA, Robertson H, Draper B, Chalkley Androgen receptor actions modify skin structure and Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez S, Daylight G, Cumming R, Bennett H, Jackson Pulver chemical carcinogen-induced skin cancer susceptibility P, Brown RH, Jr., Nomoto M, Elenius K, Rouleau GA, L and Broe GA in mice . Horm Cancer 6 (1): 45-53, 2015 . PMID:25563841 Fujiyama A, Morishita S, Goto J and Tsuji S The Koori Growing Old Well Study: investigating aging ERBB4 mutations that disrupt the neuregulin-ErbB4

36 Biennial Report 2013-15 pathway cause amyotrophic lateral sclerosis type 19 . Tropoelastin incorporation into a dermal regeneration Yeap BB, Knuiman MW, Divitini ML, Handelsman DJ, Am J Hum Genet 93 (5): 900-905, 2013 . PMID:24119685 template promotes wound angiogenesis . Adv Healthc Beilby JP, Beilin J, McQuillan B and Hung J Mater 4 (4): 577-584, 2015 . PMID:25469903 Differential associations of testosterone, Tan AG, Mitchell P, Rochtchina E, Flood VM, Cumming dihydrotestosterone and oestradiol with physical, RG and Wang JJ Wierman ME, Auchus RJ, Haisenleder DJ, Hall JE, metabolic and health-related factors in community- Serum homocysteine, vitamin B12, and folate, and the Handelsman D, Hankinson S, Rosner W, Singh RJ, dwelling men aged 17-97 years from the Busselton prevalence and incidence of posterior subcapsular Sluss PM and Stanczyk FZ Health Survey . Clin Endocrinol (Oxf) 81 (1): 100-108, cataract . Invest Ophthalmol Vis Sci 56 (1): 216-220, Editorial: the new instructions to authors for the reporting 2014 . PMID:24428256 2015 . PMID:25406287 of steroid hormone measurements . Mol Endocrinol 28 (12): 1917, 2014 . PMID:25354217 Yong A, Pennings G, Wong C, Javadzadegan A, Tey S, Ahmad-Annuar A, Drew AP, Shahrizaila N, Brieger D, Lowe H, Qi M, Behnia M, Krilis S and Nicholson GA and Kennerson ML Wierman ME, Auchus RJ, Haisenleder DJ, Hall JE, Kritharides L Analysis of dynein intermediate chains, light intermediate Handelsman D, Hankinson S, Rosner W, Singh RJ, Intracoronary upregulation of platelet extracellular chains and light chains in a cohort of hereditary Sluss PM and Stanczyk FZ matrix metalloproteinase inducer (CD147) in coronary peripheral neuropathies . Neurogenetics 15 (4): 229-235, The new instructions to authors for the reporting of disease . Int J Cardiol 166 (3): 716-721, 2013 . 2014 . PMID:25028179 steroid hormone measurements . Horm Cancer 5 (6): PMID:22192282 357, 2014 . PMID:25389069 Traini M, Quinn CM, Sandoval C, Johansson E, Yong AS, Layland J, Fearon WF, Ho M, Shah MG, Schroder K, Kockx M, Meikle PJ, Jessup W and Wilder SM, Le Couteur DG and Simpson SJ Daniels D, Whitbourn R, Macisaac A, Kritharides L, Kritharides L Diet mediates the relationship between longevity and Wilson A and Ng MK Sphingomyelin phosphodiesterase acid-like 3A reproduction in mammals . Age (Dordr) 35 (3): 921-927, Calculation of the index of microcirculatory resistance (SMPDL3A) is a novel nucleotide phosphodiesterase 2013 . PMID:22237559 without coronary wedge pressure measurement in the regulated by cholesterol in human macrophages . J Biol presence of epicardial stenosis . JACC Cardiovasc Interv Chem 289 (47): 32895-32913, 2014 . PMID:25288789 Williams KL, Fifita JA, Vucic S, Durnall JC, Kiernan 6 (1): 53-58, 2013 . PMID:23347861 MC, Blair IP and Nicholson GA Tu J, Henneicke H, Zhang Y, Stoner S, Cheng TL, Pathophysiological insights into ALS with C9ORF72 Zhao B, Choi JP, Jaehne M, Gao YR, Desai R, Schindeler A, Chen D, Tuckermann J, Cooper MS, expansions . J Neurol Neurosurg Psychiatry 84 (8): 931- Tuckermann J, Zhou H, Handelsman DJ and Seibel MJ and Zhou H 935, 2013 . PMID:23463871 Simanainen U Disruption of glucocorticoid signaling in chondrocytes Glucocorticoid receptor in prostate epithelia is delays metaphyseal fracture healing but does not affect Wright DB, Ng KS, Keshava A and Gladman MA not required for corticosteroid-induced epithelial normal cartilage and bone development . Bone 69 12-22, An unusual cause of large bowel obstruction . Colorectal hyperproliferation in the mouse prostate . Prostate 74 2014 . PMID:25193158 Dis 15 (1): e60-61, 2013 . PMID:22697806 (10): 1068-1078, 2014 . PMID:24862220

Turner MR, Hardiman O, Benatar M, Brooks BR, Wu LE, Meoli CC, Mangiafico SP, Fazakerley DJ, Zheng Y, Basel D, Chow SO, Fong-Yee C, Kim S, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Cogger VC, Mohamad M, Pant H, Kang MJ, Powter Buttgereit F, Dunstan CR, Zhou H and Seibel MJ Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash E, Burchfield JG, Xirouchaki CE, Mikolaizak AS, Targeting IL-6 and RANKL signaling inhibits prostate M, Talbot K, Traynor BJ, Van den Berg LH, Veldink Stockli J, Kolumam G, van Bruggen N, Gamble JR, Le cancer growth in bone . Clin Exp Metastasis 31 (8): 921- JH, Vucic S and Kiernan MC Couteur DG, Cooney GJ, Andrikopoulos S and James 933, 2014 . PMID:25223386 Controversies and priorities in amyotrophic lateral DE sclerosis . Lancet Neurol 12 (3): 310-322, 2013 . Systemic VEGF-A neutralization ameliorates diet- Zheng Y, Chow SO, Boernert K, Basel D, Mikuscheva PMID:23415570 induced metabolic dysfunction . Diabetes 63 (8): 2656- A, Kim S, Fong-Yee C, Trivedi T, Buttgereit F, 2667, 2014 . PMID:24696450 Sutherland RL, Dunstan CR, Zhou H and Seibel MJ Upton DH, Fuller ES, Colvin EK, Walters KA, Jimenez Direct crosstalk between cancer and osteoblast M, Desai R, Handelsman DJ, Howell VM and Allan CM Yang S, Fifita JA, Williams KL, Warraich ST, lineage cells fuels metastatic growth in bone via auto- Granulosa Cell-Specific Brca1 Loss Alone or Combined Pamphlett R, Nicholson GA and Blair IP amplification of IL-6 and RANKL signaling pathways . J with Trp53 Haploinsufficiency and Transgenic FSH Mutation analysis and immunopathological studies Bone Miner Res 29 (9): 1938-1949, 2014 . PMID:24676805 Expression Fails to Induce Ovarian Tumors . Horm Cancer of PFN1 in familial and sporadic amyotrophic lateral 2015 . PMID:25943777 sclerosis . Neurobiol Aging 34 (9): 2235 e2237-2210, Zheng LZ, Cao HJ, Chen SH, Tang T, Fu WM, Huang L, 2013 . PMID:23635659 Chow DH, Wang YX, Griffith JF, He W, Zhou H, Zhao Vasikaran SD, Chubb SP, Ebeling PR, Jenkins N, W, Zhang G, Wang XL, Qin L. Jones GR, Kotowicz MA, Morris HA, Schneider HG, Yeap BB, Alfonso H, Chubb SA, Gauci R, Byrnes E, Blockage of Src by specific sirna as a novel therapeutic Seibel MJ and Ward G Beilby JP, Ebeling PR, Handelsman DJ, Allan CA, strategy to prevent destructive repair in steroid- Harmonised Australian Reference Intervals for Serum Grossmann M, Norman PE and Flicker L associated osteonecrosis in rabbits . J Bone Miner Res PINP and CTX in Adults . Clin Biochem Rev 35 (4): 237- Higher serum undercarboxylated osteocalcin and other 2015 [Epub ahead of print] . PMID: 25917347 242, 2014 . PMID:25678728 bone turnover markers are associated with reduced diabetes risk and lower estradiol concentrations in older Vester A, Velez-Ruiz G, McLaughlin HM, Program men . J Clin Endocrinol Metab 100 (1): 63-71, 2015 . NCS, Lupski JR, Talbot K, Vance JM, Zuchner S, Roda PMID:25365314 RH, Fischbeck KH, Biesecker LG, Nicholson G, Beg AA and Antonellis A Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, A loss-of-function variant in the human histidyl-tRNA Hankey GJ, Almeida OP, Golledge J, Norman PE and synthetase (HARS) gene is neurotoxic in vivo . Hum Mutat Flicker L 34 (1): 191-199, 2013 . PMID:22930593 In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher Voukelatos A, Merom D, Sherrington C, Rissel C, dihydrotestosterone with reduced ischemic heart Cumming RG and Lord SR disease mortality, while estradiol levels do not predict The impact of a home-based walking programme on falls mortality . J Clin Endocrinol Metab 99 (1): E9-18, 2014 . in older people: the Easy Steps randomised controlled PMID:24257908 trial . Age Ageing 44 (3): 377-383, 2015 . PMID:25572426 Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, Vucic S, Nicholson GA, Chio A and Kiernan MC Hankey GJ, Golledge J, Flicker L and Norman PE Apparent anticipation in SOD1 familial amyotrophic Lower plasma testosterone or dihydrotestosterone, lateral sclerosis . Amyotroph Lateral Scler but not estradiol, is associated with symptoms of Frontotemporal Degener 14 (5-6): 452-456, 2013 . intermittent claudication in older men . Clin Endocrinol PMID:23414135 (Oxf) 79 (5): 725-732, 2013 . PMID:23509861

Wang T, Li J, Jin Z, Wu F, Li Y, Wang X, Zhou H, ZhouQ Yeap BB, Alfonso H, Chubb SA, Hankey GJ, Dynamic Frequency of Blood CD4+CD25+ Regulatory T Handelsman DJ, Golledge J, Almeida OP, Flicker L Cells in Rats with Collagen-induced Arthritis Korean J and Norman PE Physiol Pharmacol . 2015; 19(2): 83-8 . PMID:25729268 In older men, higher plasma testosterone or dihydrotestosterone is an independent predictor Wang Y, Mithieux SM, Kong Y, Wang XQ, Chong C, for reduced incidence of stroke but not myocardial Fathi A, Dehghani F, Panas E, Kemnitzer J, Daniels R, infarction . J Clin Endocrinol Metab 99 (12): 4565-4573, Kimble RM, Maitz PK, Li Z and Weiss AS 2014 . PMID:25268392

Biennial Report 2013-15 37 Financial Performance

38 Biennial Report 2013-15 Board

Prof Diana Horvath AO (Chair)

Diana retired with over 40 years broad experience in the health care industry . Her appointments & awards included: heading the NSW Community Health Program; Medical Director & then General Superintendent at RPAH; 20 years on the council of the Australian Hospital Assocn (now Aust Healthcare Assn) & held the position of National President; an International Fellow of King’s Fund College in London; Director of Health Services at Eastern Sydney Health; the first woman to chair the NH&MRC; Commissioner with the Health Insurance Commission; appointed a governor of Ascham School in Darling Point; was for 14 years CEO of Central Sydney Health (later Sydney South West); established the Clinical Streams of Care model in Australia for which she was awarded the International Hospital Assocn award for Managerial Innovation; was a member of the Trade Policy Advisory Council of several Federal ministers; as CEO set up the Australian Commission for Safety & Quality in Health Care; and board member of the Chris O’Brien Lifehouse (designated National Cancer Centre) .

She was made an Officer in the Order of Australia (1995) for her contribution to health & health services management; awarded the Sid Sax Medal; the Centenary of Federation medal, & made an Adjunct Professor at University of Sydney .

Professor Robert Lusby AM (Deputy Chair)

Professor Robert Lusby was the head of the University of Sydney Clinical School at Concord Hospital and an Associate Dean of the Faculty of Medicine till January 2015 . He is a Vascular Surgeon and was head of the vascular surgical department of Concord Hospital . He has been president of the International Cardiovascular Society Australian and New Zealand Society . Professor Lusby has served with the Australian Army Medical Corp with deployments to Rwanda with the United Nations, Bougainville and East Timor with Interfet . Colonel Lusby has been Consultant Surgeon to the Australian Army and the Australian defence Force . Professor Lusby was a Board member of Macquarie and Northern Area Health Services, a councillor of the NSW branch of the Australian Medical Association and chairman of its Ethics committee .

He was a foundation member of the Post Graduate Medical Council . Professor Lusby is proprietor of Tintilla Estate wines in the Hunter Valley .

He was awarded Member of the Order of Australia in 2015 for his outstanding services to medicine as a cardiovascular surgeon, clinician, educator and researcher .

Biennial Report 2013-15 39 Professor David Handelsman

David Handelsman is Professor of Reproductive Endocrinology and Andrology and founding Director of the ANZAC Research Institute since 1998 . He is an international expert in Andrology, the study of male reproductive health, medicine and biology . After Endocrinology training and NHMRC & Wellcome Trust postdoctoral fellowships, he become Australia’s first Professor of Andrology (1996) and created its first hospital Andrology Department (1999) at Concord Hospital . As the most highly cited author internationally on “androgens” and “testosterone”, he has over 500 peer-reviewed papers . His research focuses on androgen physiology, pharmacology and toxicology most recently in genetic models of androgen action, steroid mass spectrometry, anti-doping science, and clinical and epidemiological androgen pharmacology .

Dr Teresa Anderson

Dr Teresa Anderson is the Chief Executive of Sydney Local Health District and has had over 30 years experience in the public health system as a clinician and manager . Extensive experience in the management of health services including General Manager, Liverpool Hospital; and Director, Clinical Operations, former Sydney South West Area Health Service . Board Memberships include: Ingham Institute for Applied Medical Research; Centenary Institute; Heart Research Institute; and Centre for Primary Health Care and Equity .

Professor Bruce Robinson AM

Professor Robinson was appointed Dean, Faculty of Medicine, University of Sydney, in May 2007 . He is an Endocrinologist and Head of the Cancer Genetic Laboratory in the Kolling Institute . While undertaking studies for a Masters of Science degree he undertook molecular research work at the Brigham and Women’s Hospital and the Children’s Hospital, Harvard Medical School from 1986-1989 and was awarded a Doctorate of Medicine from the University of Sydney in 1990 . He has developed and led the Cancer Genetics’ Laboratory since 1990 and has supervised over 20 doctoral and masters students working on the genetic basis for tumour formation and gene therapy . In 2003 Professor Robinson was awarded the Daiichi Prize by the Asia and Oceania Thyroid Association for this work on the pathogenesis of thyroid cancer .

Professor Robinson has a strong interest in furthering relations between Australia and Asia and he is the Founding Chairman of Hoc Mai, the Australia Vietnam Medical Foundation, which sponsors and supports medical nursing, allied health and scientific exchanges between Australia and Vietnam . He is a Fellow of the Australian Institute of Company Directors .

40 Biennial Report 2013-15 Professor Ben Freedman OAM (Alternate for Prof Robinson)

Ben Freedman is Professor of Cardiology at Concord Hospital and Deputy Dean of the Sydney Medical School at Sydney University . He was previously Head of Department of Cardiology at Concord Hospital and is Head of the Vascular Biology Group of The Anzac Research Institute . He is a member of a number of boards including the Heart Research Institute, Bosch Institute, Asbestos Diseases Research Foundation, Centre for Vascular Research, Microsearch Foundation, Sydney Burns Foundation, and the Heart Foundation of Australia Research Committee, and Chairs the advisory boards of the Northern Rivers University Centre of Rural Health (North Coast), Broken Hill University Department of Rural Health, and Dubbo/Orange Rural Clinical School of the University of Sydney . Professor Freedman is a Fellow of the American College of Cardiology (FACC), the European Society of Cardiology (FESC), and the Cardiac Society of Australia and New Zealand (FCSANZ) . He was secretary of the CSANZ in the mid 1990s, and was Scientific Chairman of the successful World Congress of Cardiology held in Sydney in 2002 . In 2011 he was awarded the Order of Australia Medal (OAM) in honour of his contributions to research, education, and clinical practice .

Professor Arthur Conigrave (Alternate for Prof Robinson)

Prof Arthur Conigrave is an endocrinologist specializing in disorders of calcium metabolism; a research scientist with internationally recognized expertise in the structure and function of the calcium-sensing receptor and in mechanisms of regulation of parathyroid hormone secretion; Deputy Dean of Sydney Medical School and lectures in Medical Biochemistry and Molecular Endrocrinology for the University of Sydney Medical Program .

Mr Paul Levins

President of the Australia and New Zealand office of Intellectual Ventures, a $5bn Seattle based company that invests in invention . I have worked in the fields of business, communication, negotiation, government and the not for profit sector across a diverse policy field for over 25 years . I am a current board member of auDA (Australia’s .au domain name coordinator) .

I am an Honorary Associate and guest lecturer at the Graduate School of Government at the University of Sydney and a Key commentator with the Global Internet Business Coalition .

Biennial Report 2013-15 41 Ms Kerry Hogan-Ross

Kerry Hogan-Ross is a lawyer and accredited mediator . She was a partner of a national law firm, DLA Phillips Fox and DLA Piper for 12 years . She is also on the board of Force Majeure, a not for profit dance theatre company where she is the company Secretary . Kerry has been a commercial and insurance litigator for more than twenty three ears and advises corporations, insurers, professionals and company directors in a wide variety of areas . Kerry’s professional indemnity practice includes claims against solicitors and doctors .

Dr Katherine Moore

Dr Katherine Moore is the Director of Clinical Governance in the Sydney Local Health District . She has held a number of roles within the profession of occupational therapy including president of the NSW Occupational Therapy Association, a member of the university accreditation panel, and as a previous member of the overseas qualifications assessment committee .

Katherine has worked as an occupational therapist in aged care rehabilitation, and has managed occupational therapy departments in acute and subacute settings . She has also been a Director of Allied Health and a Community Health Director in the former Sydney South West Area Health Service . Katherine has been a surveyor with the Australian Council on Healthcare Standards (ACHS) since 2002 and has a particular interest in quality and safety in healthcare .

Dr Katherine Moore is a practitioner member from New South Wales .

Dr Tim Sinclair

Dr Tim Sinclair is the General Manager of Concord Repatriation General Hospital, Sydney Local Health District . He holds a Doctor of Business Administration, a Masters in Health Services Management and a Bachelor of Applied Science (Health Information Management) . Tim also successfully completed the Graduate Health Management Training Program . Prior to that appointment he was the General Manager at Balmain Hospital and he has previously held a number of senior positions with the then Sydney South West Area Health Service including the Associate Director of Clinical Operations and the Manager, Operational Initiatives . He is also a Director on the ANZAC Health and Medical Research Foundation and an Advisory Board Member of the Australian Institute of Health Services Management . In 2013 Tim was also the recipient of the Institute of Public Administration Australia award for Individual Excellence and the Anthea Kerr Award .

42 Biennial Report 2013-15 Dr Ilona Cunningham

Senior Staff Specialist, Head of Department, Department of Haematology- Concord Repatriation General Hospital . Fellow of the Royal Australasian College of Physicians, Haematology Society of Australia and New Zealand, Australasian Leukaemia and Lymphoma Study Group, Australasian Society of Thrombosis and Haemostasis and American Society of Haematology .

Mr George Elias

Principal of Elias Financial Services and is an Authorised Representative of Count Financial Limited . George has been providing financial / accounting advice as principal of Elias Financial Services since July 1991 to a wide range of personal and small/medium business clients, and he has been providing investment advice as an authorized representative of Count since June 1992 . In February 2000, CPA Australia designated George a Financial Planning Specialist . George also specialises in tax effective loan structuring drawing on his experience as a tax advisor and mortgage broker .

Prof Andrew McLachlan

Board and organisation membership Chair, Sydney Local Health District –Concord Hospital Ethics Committee: Drug and Therapeutics Committee, Concord Hospital: Anti-Doping Rule Violation Panel, Department of Health, Australian Government Member, Australia Therapeutic Goods Advisory Council Chair, Pharmaceutical Subcommittee, Advisory Committee on Prescription Medicines (ACPM), Therapeutic Goods Administration Theme Leader, Health Services Research and Patient Safety, Faculty of Pharmacy, USyd Secretary, NSW Therapeutics Advisory Group Member, Medication Reference Group, Australian Commission on Safety and Quality in Health Care, Director, McLachlan PK Consulting Pty Ltd (consulting company)

A/Prof Meng Ngu

Senior Staff Specialist, Head of Department, Department of Gastroenterology and Hepatology, Chairman, Ambulatory Care & Endoscopy at Concord Repatriation General Hospital and Clinical Associate Professor, University of Sydney Concord RGH Clinical School and Trustee and member of Management Committee of the Rights of Private Practice Trust Fund .

He is a Member of the following Professional Associations: Fellow of the Royal Australasian College of Physicians; Fellow of American Gastroenterological Association; Gastroenterological Society of Australia; Australian Medical Association; Australian Chinese Medical Association; European Association for the Study of Liver Diseases and Asian Pacific Association for the Study of Liver Diseases .

Biennial Report 2013-15 43 Donor Honor Roll

CORPORATIONS

University of Sydney - Churm Bequest ...... $75,000 Stephen John Bell ...... $5,000

Gwynvill Trading Pty Ltd ...... $50,000 Miss Maria Lydaki ...... $4,000

Bartent Pty Ltd ...... $25,000 Mrs A Mildenhall ...... $4,000

The Beeren Foundation ...... $12,000 John C Gordon ...... $4,000

The Lin Huddleston Charitable Foundation ...... $10,000 Mr Stephen Collis ...... $2,000

Pamela Churm Bequest ...... $10,000 Claudine Siou ...... $2,000

Ovlov Marine Ltd ...... $8,485 Debora Felman ...... $2,000

Myasthenia Gravis Friends and Support Group WA Inc . . . $3,500 Davis Paul Raymond ...... $1,840

N . Sprainger & Co ...... $2,000 Dr Ross Bradbury ...... $1,040

L H Ainsworth ...... $1,000 John C Gordon ...... $1,000

Beta Sigma Phi Delta Master Sydney ...... $760 Wendy Cleary ...... $1,000

Caring Funerals Pty Ltd ...... $285 Jenny Spaliviero ...... $950

Falk Gregory Leighton ...... $750 COMMUNITY ORGANISATIONS Ralph Butcher ...... $600 Charcot-Marie-Tooth Association of Australia ...... $19,508 Heath Owen ...... $500 Beeren Foundation ...... $15,000 J & A Collins ...... $500 Ghosh Family Foundation ...... $5,353 Gregory Falk ...... $400 Chester Hill -Carramar Sub Branch RSL ...... $2,250 Mr Alan Davidson ...... $400 Rotaract Club of Burwood ...... $1,559 Dr P and DJ Bass ...... $250 Beta Sigma Phi, Delta Master Sydney ...... $1,000 Janice Hooper ...... $200 Combined Services RSL (Sydney) ...... $500 Brigadier RW Morris ...... $150 Campsie RSL Sub Branch ...... $500

FOTARI

Dr Varoe Legge ...... $130,000

Prof Marc Gladman ...... $60,000

Jill Laurent ...... $35,000

Mr Julius M Opit ...... $25,000

Late Cyril George Hawke Bequest ...... $20,690

Ian Thomas Palmer ...... $10,000

Prof Markus & Katrin Seibel ...... $10,000

44 Biennial Report 2013-15 GIVING OPPORTUNITIES

ABOUT US □ Yes. I would like to help ANZAC Health & Medical Research Foundation.

□ I would like to meet a representative from the Foundation to discuss making a bequest.

Vision □ I have already remembered ANZAC Health & Medical Research Foundation in my Will.

To provide Leadership and excellence in health and medical research activities throughout Australia, □ Please send me more information about the Foundation’s Bequest Program, including the recognition of benefactors. with a focus on aging, to improve the future health and medical care for the Australasian community. In so doing, the Foundation will provide a lasting legacy to the veterans and their families who have □ A gift to continue vital scientific research. created the society we have today. □ Please send me more information on the FOTARI.

Mission I / We wish to make a donation of $______to ANZAC Health & Medical Research Foundation.

• To establish and operate a state-of-the-art biomedical research institute on the campus of Concord Name:______Hospital that is affiliated with the University of Sydney. Address:______

• To encourage, collaborate in and undertake basic, clinical and epidemiological research, with a ______particular focus on ageing, that aims to improve health and medical care and is dedicated to the memory of our war veterans and their families. Postcode:______

Telephone Home:______Work:______Mobile: ______• To gain and optimise support from the wider community in order to facilitate our vision. Email:______• To provide leadership and excellence in biomedical research in national and international arenas. Payment is by: • To foster education and training in relevant research and health disciplines. □ Cheque □ Money Order □ Visa □ Bankcard □ Mastercard

Number: ______/ ______/ ______/ ______Expir y: _____ / ______

Signature:______

Date: ______/ ______/ ______

For further information contact: ANZAC Health & Medical Research Foundation ANZAC Research Institute Hospital Road CONCORD NSW 2139 Telephone: (02) 9767 9100 or Facsimile: (02) 9767 9101 www.anzac.edu.au Email: [email protected] All gifts over $2.00 are tax deductible

Cover image: Courtesy Lynley Pilon. Annual Report 2009 ANZAC Research Institute

ANZAC Research Institute

ANZAC Research Institute ANZACHospital ResearchRoad, Concord Institute Hospital Hospital SydneyRoad, ConcordNSW 2139 Hospital Sydney NSW 2139 Telephone: (02) 9767 9100 or Facsimile: (02) 9767 9101 Telephone:www.anzac.edu.au (02) 9767 9100 Email: or Facsimile: [email protected] (02) 9767 9101 www.anzac.edu.au Email: [email protected] ANZAC Health & Medical Research Foundation ABN 48 066 780 005 ANZAC ANZAC Health & Medical Research Foundation ABN 48 066 780 005 Biennial Report 2013-15 Research Institute

ANZAC Research Institute