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Garvan Institute of Medical ResearchAnnual Report 2008
Garvan Institute of M
edical Research Annual Report 2
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Garvan's mission is to make significant contributions to medicalresearch that will change the directions of science and medicine andhave major impacts on human health. Garvan strives to enhance anddevelop research programs that combine fundamental science withstrong clinical interactions.
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CONTENTS
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_ 03 Who We Are, What We Do
_ 04 Research Highlights
_ 07 Garvan at a Glance
_ 10 Chairman's Report
_ 12 Executive Director's Report
_ 14 Garvan Research Foundation Chairman's Report
_ 17 Organisational Chart
Research Programs_ 19 Cancer_ 27 Diabetes and Obesity_ 33 Immunology and Inflammation_ 39 Osteoporosis and Bone Biology_ 43 Neuroscience_ 47 Autoimmunity Research Unit_ 51 Pituitary Research Unit
_ 55 Core Research Facilities
_ 57 Management Highlights
_ 59 Business Development
Garvan Community_ 60 Life Governors_ 60 Partners for the Future_ 60 Volunteers_ 61 Garvan Supporters_ 63 Bequests
Governance_ 65 Institute Governance_ 67 Foundation Governance
_ 72 Publications
_ 81 Financial Highlights
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WHO WE ARE, WHAT WE DO 03
WHO WE ARE, WHAT WE DO
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Significant breakthroughs have beenachieved by Garvan scientists in theunderstanding and treatment of diseasessuch as:
_ Cancer_ Diabetes and obesity_ Alzheimer's and Parkinson's disease_ Osteoporosis_ Arthritis and asthma_ Pituitary disorders
Garvan's ultimate goal is prevention andcure of these major diseases.
The Garvan Institute of Medical Research is a world leader in itsfield, pioneering study into some of the most widespread diseasesaffecting our community today. Research at Garvan is focused uponunderstanding the role of genes in health and disease as the basisfor developing future cures.
04 RESEARCH HIGHLIGHTS
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RESEARCH HIGHLIGHTS
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_ Diabetes researchers found a significant missing link in our knowledge about insulin andhow it helps cells absorb glucose. We showed that insulin activates a 'motor protein' thatin turn drives glucose transport molecules to the cell surface.
_ Our Dubbo Osteoporosis Epidemiology Study demonstrated that low levels oftestosterone in men double their risk of bone fracture; that men with prostate cancerface a 50% higher risk of fracture, which increases to nearly 100% if they are receivingandrogen deprivation therapy; and that osteoporotic fractures increase a person's risk ofdying, even after relatively minor fractures if that person is over 75. The Osteoporosisand Bone Biology Program also devised a web-based fracture risk calculator, which hasbeen widely adopted by the medical community throughout Australia.
_ To remain healthy, we must maintain exactly the right number of B cells, the white bloodcells that produce antibodies. Garvan immunologists identified two proteins made insideB cells, TRAF2 and TRAF3, that are essential for maintaining this important balance withinour immune systems. When the balance fails, we become prone to developing certaincancers or autoimmune diseases.
_ An international team of scientists from Garvan, Harvard Medical School and the MaxPlanck Institute in Germany, identified processes that are heavily implicated in humanmultiple myeloma and other B cell cancers, moving us closer to developing quick testsand readouts that could help in the tailored treatment of patients.
_ Neuroscience researchers showed that a hormone released naturally from the gut after ameal could be used to treat obesity and Type 2 diabetes. The hormone peptide YY (PYY)acts on the brain, contributing to a feeling of satiety, suggesting the use of this hormoneas a weight loss medication.
_ Researchers concluded that low levels of PYY could be used as a predictor for thedevelopment of Type 2 diabetes. Clinical studies showed that people with a family historyof Type 2 diabetes, but not yet showing signs of insulin resistance themselves, producelower levels of PYY after eating, a very early sign of pre-diabetes.
_ Cancer researchers found that by 'switching off' the Id1 gene, produced by the mostaggressive forms of breast cancer, it is possible to induce a state of 'senescence', orpermanent sleep, within a tumour, preventing it from growing or spreading.
_ Garvan and CSIRO signed a three-year collaboration agreement to investigate importantcellular processes, including those impaired by diseases such as diabetes. They will beusing a new computer vision system they developed jointly to watch intricate cellularprocesses in real time.
_ Immunology researchers working on Type 1 diabetes uncovered a process with thepotential to alter the body's response to anything it perceives as not 'self', by stimulatingthe production of a class of immune cells known as T regulatory cells. The finding givesus hope that one day it may be possible to alter the immune system to accept tissuetransplants without the need for any immunosuppression.
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RESEARCH HIGHLIGHTS 05
_ Garvan epigenetics expert, Professor Susan Clark, was the Australian contributor to aNature article about the global taskforce taking shape for the human epigenomeproject. Professor Clark is one of the founding members of the Australian EpigenomeAlliance, formed in 2008.
_ Cancer researchers identified a way to 'switch off' Gab2, a key protein in the molecularprocesses that trigger breast cancer and certain forms of leukaemia. Gab2 operatesdownstream of a major breast cancer oncogene, HER2, the target of the drugHerceptin.
_ Teams from Garvan's Diabetes Program and the Shanghai Institute of Materia Medicapulped roughly a tonne of fresh bitter melon, a Chinese vegetable, and extracted fourvery promising bioactive components that explain why it is has been used in Chinesemedicine for hundreds of years. It now promises to be an effective treatment for Type2 diabetes.
_ In collaboration with researchers from Canberra's John Curtin School of MedicalResearch, Garvan immunologists worked out why people with Hyper IgE Syndrome, or'Job's Syndrome', are unusually susceptible to certain common infections. By revealingthe exact molecular mechanisms involved, they were given clues as to why some'healthy' people are more prone to these infections than others.
_ A study undertaken by researchers in our Pituitary Research Unit demonstrated the'placebo effect' in sport. If athletes believe they are using a performance-enhancingdrug, they may think their performance improves, and in some it can, even if they areactually taking a dummy drug.
_ Until now, it was thought that the processes leading to the death of insulin-secretingpancreatic cells were similar in both types of diabetes. Researchers in our DiabetesProgram showed that the process is quite different in the two diseases. They alsoidentified a promising therapeutic target for people with Type 2 diabetes.
_ Our bodies rely on the production of potent, or 'high affinity', antibodies to fightinfection. The process is very complex, yet Garvan immunologists have discoveredthat it hinges on a single molecule known as IL-21, a growth factor, without which itcannot function. This finding suggests ways to strengthen the body's natural defences.
_ Seminal work within the Cancer Program, correlating expression of certainfunctionally-related oestrogen-regulated genes with predictable clinical outcomes,should help clinicians decide which women with breast cancer will make goodcandidates for anti-oestrogen therapies, such as tamoxifen, and which will not.
_ Clinicians have known for some time that people treated for HIV also become muchmore susceptible to diabetes and heart disease. A study by clinical researchers in ourDiabetes group, in collaboration with St. Vincent's Hospital's Centre for Immunology,showed some of the reasons why - enabling better patient management andmonitoring.
_ Immunology researchers identified a process, a synergistic encounter between twomolecules, IL-4 and IL-21, that may account for the extreme allergic reactions somepeople experience. By silencing at least one of these molecules, it may be possible totreat allergies.
_ The Osteoporosis and Bone Biology Program collaborated with the Icelandic geneticscompany, deCode, in an extensive multi-nation genome-wide search to find the geneslinked to osteoporosis and fracture. Five regions of interest were identified that appearto warrant further scientific investigation.
_ Metabolic experts in our Diabetes Program, in collaboration with Melbourne's Baker IDI Heart and Diabetes Institute made a finding that is likely to be an importantmilestone in understanding the mechanisms of obesity related insulin resistance, aprecursor of Type 2 diabetes. They have manipulated one important protein to helpmuscle burn fats.
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GARVAN AT A GLANCE 07
GARVAN AT A GLANCE
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Research Collaborations
New treatments 23%
Drug discovery tools 10%
Therapeutics 3%
New drug targets 23%
Diagnostics 41%
08 GARVAN AT A GLANCE
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Scientific Publications
Impact factor of scientific publicationsEach paper published constitutes a new piece of knowledge, and scientistsaim to publish in the most highly regarded journal in their area of research.Each journal has an “impact factor” which is a common measure of its relativeimportance within a specific discipline. Research organisations use “averageimpact factor” measurements to determine the overall significance of theirresearch output. For example, in 2008 Garvan achieved an “average impactfactor” greater than 8 for the top 75% of its publications. This is a veryrespectable tally, well above the international benchmark.
Patent Portfolio by Category
0
1
2
3
4
5
6
7
2004 2005 2006 2007 2008
$3,539,000
$2,790,000
$4,158,000
$5,370,000
$6,966,000
Total Income (excluding bequests)received by Garvan Research Foundation
Inco
me
$ m
il
0
20
40
60
80
100
120
140
160
180
2003 2004 2005 2006 2007 2008
104
115
135
151 153
185
Num
ber
of P
ublic
atio
ns
190
Donations are particularly importantin two respects:
_ They provide seed funding fornovel work, which may not attractother support for several years
_ They fund core items of equipmentthat are typically not covered byresearch grants
Growth in Philanthropic Support
$ Mil $ Mil
Year NHMRC Other
2003 8,465 5,636
2004 9,244 6,222
2005 12,080 8,685
2006 13,832 8,184
2007 16,682 8,530
2008 18,695 9,1590
5
10
15
20
25
30
2003 2004 2005 2006 2007 2008
Inco
me
$ m
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GARVAN AT A GLANCE 09
Growth in Staff Numbers
One of the major challenges facingsuccessful research institutes aroundAustralia remains the “gap” between thetotal costs of doing research and thefunding provided by competitive researchgrants. For every dollar of researchfunding awarded, another 70 cents isrequired to carry out the research.
Peer Reviewed Grant Income
Competitive grants 61%
Other grants 10%
Donations 10%
NSW Government 9%
Industry partners 2%
Other income 8%
2008 $47 Million
…:
0
100
200
300
400
500
2003 2004 2005 2006 2007 2008
291308
373403
433
479
Num
ber
of S
taff
_ Average age 38
_ Researchers from 55 countries
_ Research staff 61% female,39% male
Staff Breakdown 2007 2008
Researchers 301 314
Students 61 68
Scientific Facility Staff 44 62
Secretarial & Administration 27 35
Total 433 479
Operating Income
Our funding from the National Healthand Medical Research Council (NHMRC)rose to a record $18.7m, up from$16.7m in 2007. Overall, peer reviewedgrant funding increased toapproximately $27.9m.
10 CHAIRMAN'S REPORT
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CHAIRMAN’S REPORT
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2008Garvan continued its excellent record of research success in 2008, as measured bygrants, publication impacts and international awards, and we are justly proud of ourfaculty and staff.
Several important strategic initiatives came to fruition during the year, including:
_ completion of a major review of the Institute's future directions by an international panel
_ the opening of our major breeding and holding facility for experimental mouse modelsin the Southern Highlands (Australian BioResources), and
_ rapid progress in development of plans for the new Garvan St Vincent's CampusCancer Centre.
Financial PerformanceGarvan's operating income grew to approximately $47m in 2008 from $42m theprevious year, an increase that is testament to the quality of Garvan research.Philanthropic support through the Garvan Research Foundation, essential for providingcritical equipment and facilitating new initiatives, continued to be strong, with over$4.7m in general and specific grants contributed to research programs and almost$4.0m into the long term endowment of the Institute.
Our PeopleOnce again my sincere thanks and admiration are extended to Professor John Shine, hissenior management team, faculty and staff.
I am also most grateful for the commitment and counsel of the Board of Directors. The only change to the composition of the Board during the year was the resignation of Ms Mary Foley, following her retirement from the position of Chief Executive of St Vincents & Mater Health. During her tenure on the Board, Ms Foley championed theclose relationship between Garvan and St Vincent's. We welcomed the new CEO of St Vincents & Mater Health, Mr Steven Rubic, to the Board in the latter part of 2008.
Strategic ReviewIn 2008, the Board commissioned an independent review of the Institute's programsand directions, assembling a review panel of leading international scientists for thisimportant task. Chaired by Professor Bruce Dowton, former Dean of the UNSW MedicalSchool and now Senior Vice President at Harvard Medical International, the panelcompleted its work midway through 2008. This provided a valuable strategic frameworkfor management and Board in setting future directions for the Institute. The Boardendorsed the recommendations of the Review and I am pleased to advise that theimplementation process is already well underway.
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CHAIRMAN'S REPORT 11
The Review confirmed the importance for Garvan of focusing its efforts on a fewresearch themes where it can expect to remain internationally relevant and competitive.Cancer, diabetes/metabolism, neurobiological disorders and immunology all fell into thiscategory. The Review encouraged an increasing emphasis on translational work andconfirmed the importance of the proposed Garvan St Vincent's Campus Cancer Centre.
The Review also urged Garvan to strengthen its Institute-wide culture by breaking down“research silos”. Accordingly, some important new governance and managementstructures have already been implemented and are outlined by the Executive Director inthis report.
Garvan St Vincent's Cancer Campus CentreDuring 2008, the $100m Garvan St Vincent's Campus Cancer Centre project gainedsignificant momentum. Extensive work was completed on the development of thefunctional and design briefs and the appointment of architects. Importantly, we werealso successful in attracting major philanthropic support of nearly $20m plus thecommitment of the land from the Trustees of St Vincent's Hospital.
The vision is to create a facility of international standing and world's best practice intranslational cancer research which will accelerate the rate at which new discoveries canbe trialled in the clinic. The Centre will bring together clinicians, clinical researchers andbiomedical scientists from across the campus, to improve patient outcomes via thedetection, diagnosis and treatment of cancer.
Business DevelopmentGarvan's success in basic research is being matched by progress in translating research“discoveries” into real outcomes for patients.
One important project involves a potential novel treatment for Type 2 diabetes. As thisdebilitating disorder develops, the beta cells of the pancreas fail to secrete enough insulinto regulate levels of blood sugar. Garvan's diabetes researchers have discovered that theenzyme, protein kinase C epsilon (PKCe) plays a central role in this process and thatinhibition of PKCe results in a marked improvement in insulin secretion. Accordingly, wehave entered into an agreement with a US based pharmaceutical group to evaluate newpotent PKCe inhibitors, already in clinical trials for another indication. If the results are aspositive as we expect, the compounds should enter the clinic in a short timeframe.
2009In the year ahead, we anticipate the ongoing challenges of expansion, particularly thecontinuing pressure on infrastructure. Important new initiatives, such as the cancercentre, will also require a major increase in financial and human resources.
The Board is confident that, with the support of government and the community, ourresearch will continue to have a growing impact on human health, particularly as weintegrate it even more closely with health care delivery.
Bill Ferris AC
ChairmanGarvan Institute of Medical Research
12 EXECUTIVE DIRECTOR'S REPORT
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EXECUTIVE DIRECTOR’S REPORT
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2008 was another outstanding year for Garvan in terms of significant research findings,success in obtaining competitive grants and growth in the number of papers acceptedfor publication in prestigious international journals. We published 185 peer reviewedresearch papers, the top 75% in journals with an average impact factor greater than 8.This remains above internationally accepted benchmark levels and is testament to theexcellence and commitment of our researchers.
Research publication productivity was matched by success in applications forcompetitive grants. Our funding from the National Health and Medical Research Council(NHMRC) rose to a record $18.7m, up from $16.7m in 2007. Overall, peer reviewedgrant funding increased to approximately $27.9m.
Of particular importance was our success with NHMRC Program grants for both theCancer and Diabetes and Obesity Programs. Together with renewal of a similar Programgrant for the Immunology Program in 2007, three of the Institute's major researchprograms now have guaranteed high-level support for the next five years. This allows usto think more strategically long-term.
Staff numbers across the organisation continued to grow to a total of 479. Growth wasparticularly strong in our Cancer, Immunology and Diabetes and Obesity Programs,reflecting ongoing success in competitive grant applications for new and existing projects.
Australian BioResources (ABR) The state-of-the-art holding and breeding facility for experimental mice lines at MossVale provides critical infrastructure for Australian innovation. Experimental mouse-basedmodels underpin modern medical research and biotechnology, their use growingexponentially in recent years. As a result, medical research institutes and universities areincreasingly challenged to find the resources to house and provide expert care andspecialised breeding and laboratory services for the rapidly expanding colonies. Thissituation threatens to compromise our internationally competitive research and holdback innovation in the sector.
The facility is now fully operational and already proving to be a success, fulfilling theneeds of Garvan and its initial partners across NSW. At the end of 2008, ABR heldnearly 20,000 mice, a number expected to double over the next few years.
Campus DevelopmentsAn active member of the St Vincent's Campus, Garvan values its historic and ongoingclose association with St Vincent's Hospital and its commitment to the values of theSisters of Charity.
During 2008, the new Lowy Packer Building for Victor Chang and St Vincent's researchwas officially opened, providing state-of-the-art research accommodation for over 200researchers. Like the Garvan building, the new building will house several core researchfacilities shared by all research groups on the Campus. With the decanting of VictorChang and St Vincent's researchers from space previously occupied in Garvan, we have refurbished the area to increase available research space and accommodatenew technologies.
Our joint venture with St Vincents & Mater Health to establish the Garvan St Vincent'sCampus Cancer Centre made major progress in 2008. Garvan researchers and StVincent's clinicians are united in their enthusiasm for this unique opportunity to translateour research “discoveries” into improved treatment and prevention of cancer.
2009Last year a major review was carried out examining the future directions of Garvan'sscience and optimal structure to facilitate ongoing success. This has helped shape ourthinking and planning over the next decade. We have already implemented someimportant changes to our management structure to help address the challenges ofgrowth and the increasing cross-Program nature of our research endeavours.Specifically, we have created an Executive Research Committee as the major policy andstrategic advisory body of Garvan. Chaired by the Executive Director, the committeeincludes leading researchers at varying stages of their careers, allowing a broadspectrum of Garvan researchers to help chart our future.
Other important initiatives follow the Review, including the establishment of anOperations Committee, chaired by the Chief Operating Officer, charged with enhancingcommunication between our ever increasing research base and the professional supportfunctions essential for the effective operation of the Institute. We have alsoreconstituted our Scientific Appointments and Promotions Committee to includeadditional external members as the breadth of our research activities expand. Similarly,we are appointing a Scientific Advisory Council of eminent international and nationalresearchers to help advise the institute on current and future research directions.
I look forward to reporting on the detail and successful outcomes of these new structuresin future years, as Garvan evolves to take maximum advantage of the enormousopportunities to improve quality of life that are evident in today's medical research.
Reinvigorated by the success of 2008 and strengthened by the outcomes of theReview, we will remain clearly focused on elucidating the fundamental basis of disease.We will also drive the translation of our research discoveries into new and improvedways to prevent and treat the major diseases that challenge our society.
John Shine AO FAA
Executive DirectorGarvan Institute of Medical Research
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EXECUTIVE DIRECTOR'S REPORT 13
14 GARVAN RESEARCH FOUNDATION CHAIRMAN’S REPORT
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CHAIRMAN’S REPORT
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I am delighted to report that the Foundation's results have exceeded expectations in2008 by over $2.0 million, with total income of $10.2 million - an exceptionalperformance, particularly in this economic climate.
Total gift income excluding bequests was $7.0 million, as against $4.2 million in 2006and $5.4 million in 2007, continuing the growth trajectory initiated by our CEO whenshe took up the role three years ago.
Bequests this year totalled $3.1 million. It is impossible to overstate the significance ofsuch gifts, often enabling us to put in place a 'next generation' program or core research infrastructure.
The Foundation grew its annual grant to the Institute to $926,000 and contributed$3.8 million to specific research programs or projects. We also added nearly $4.0 millionto the Institute's endowment fund.
Major giftsWe thank our major donors (some of whom choose to remain anonymous) for theirloyalty and support of our research programs.
Ms Rosemary Pryor gave $1 million to fledging projects in Neuroscience (work thatrequires up to three years of philanthropic funding before it is possible to apply forcompetitive peer-reviewed grants). Mrs Virginia Kahlbetzer continued her crucialsupport ($200,000 per year) for our lung cancer research.
Stalwart corporate supporter, the MLC Community Foundation, pledged $1 million overfive years, to support one of our core scientific facilities.
New corporate supporter, graysonline.com, committed $200,000, enabling thepurchase of a key piece of scientific equipment. Graysonline.com also auctionedjewellery from the Drs Ryan's estate, helping us raise nearly $60,000.
The John T Reid Charitable Trusts donated funds to support a new microscope for theMolecular Imaging Unit, accessed by researchers at Garvan, across the campus and atother research enterprises.
Mr Trevor and Mrs Christina Kennedy contributed the majority of their $1.0 million giftto hearing loss research in 2008. Lady (Mary) Fairfax also gave a further $500,000 tothis research.
Mr Paul and Mrs Judy Hennessy established the Stuart Furler Travel Fund. Stuart was oneof the longest-serving researchers at the Garvan until he died of pancreatic cancer. TheFund will support young researchers' travel to international conferences and laboratories.
Garvan Research Foundation
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GARVAN RESEARCH FOUNDATION CHAIRMAN’S REPORT 15
EventsThe Foundation managed several events in 2008, including the AGM, the opening ofAustralian BioResources in Moss Vale and the Institute's Open Day. On 17 August,Garvan opened its doors to over 900 visitors, showcasing disease-focused informationbooths manned by our researchers; presentations on diabetes and cancer; and a panelof distinguished guests discussing the future of science and medicine. Open Dayfeedback was excellent and we intend to run this event every second year.
Our Young Garvan Committee again delivered three forums for the 25-35 year oldprofessionals of Sydney, helping to raise awareness of the importance of medical research.
The Garvan St Vincent's Campus Cancer CentreIn addition to Garvan core business, the Foundation CEO accepted the challenge ofleading the $100 million capital campaign for the new joint venture between Garvanand St Vincents & Mater Health Sydney, the Garvan St Vincent’s Campus Cancer Centre.
We appreciate the generosity of Ms Delta Goodrem who has accepted the role ofPatron and assists with raising awareness and funds. Delta played a key role in themedia conference and Gala Dinner held on 22 October. The Dinner raised approximately $240,000.
Prior to the Dinner, a few supporters approached privately pledged around $16 millionin 2008. The Kinghorn Foundation, for example, gave $5 million to the Centre. Thesevery generous gifts are greatly appreciated.
Board and staff changesI wish to take this opportunity to thank my fellow Directors for their energy and vision,and to note several changes on the Board in 2008.
We gratefully acknowledge the contributions of retiring Directors: Mr Ross King, MrPeter Wade, Mr Phil Clark AM, the Hon Warwick Smith AM and Mr Richard Warburton AO.A special thank you goes to Richard Warburton who served on the Board for 12 years.We also welcome Mr Loftus Harris AM, Mr Brad Rees, Mr Karim Temsamani and MrGeoff Dixon to the Board.
There were several staff changes in 2008, with the Foundation continuing to grow. Wethank Rachael Stewart, who left us after three years, and welcome Mona Saade as ournew Supporter Services Coordinator.
We also welcome Dianne Lavender, Media Relations Manager, and Janice Lam, DataEntry Clerk. In her first year, Dianne achieved considerable media coverage, includingtwo 7.30 Report stories, and a community service announcement about diabetesfeaturing Marcia Hines. With 2,094 new donors joining Garvan in 2008, in addition to1,500 the previous year, Janice's position is essential.
I thank each and every Garvan supporter and look forward to retaining and deepeningour relationship with you in 2009.
Graham BradleyChairmanGarvan Research Foundation
ORGANISATION CHART
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Executive Director Prof John Shine AO FAA
Garvan Institute of Medical ResearchBoard of Directors
Chairman Mr Bill Ferris AC
Development & Support Group
Chief Operating Officer Mr John Dakin
Australian BioResources Dr Jenny Kingham
Business Development & Legal Affairs Ms Christina Hardy
Corporate ServicesMs Cate Smith
Diabetes Vaccine Development CentreMs Rowena Tucker
Finance and AccountingMs Cherry Dutton
Human ResourcesMs Deborah Pearson
Information TechnologyMr Jim McBride
OperationsMr David Keenan
Science CommunicationsMs Alison Heather
Core Research Facilities
Australian BioResourcesPeter Wills Bioinformatics CentrePieter Huveneers Molecular Imaging UnitGene Chip FacilityBiological Testing FacilityClinical Research FacilityFlow Cytometry FacilityAustralian Cancer Research Fund Unit for the Molecular Genetics of Cancer
Immunology & Inflammation
Leader Prof Charles Mackay FAA
Senior Scientists
Dr Shane GreyDr Jenny GuntonDr Cecile KingProf Jonathan Sprent FRS FAA
Dr Stuart Tangye
Diabetes & Obesity
Leader Prof David James FAA
Senior Scientists
A/Prof Trevor BidenProf Lesley Campbell AM
Prof Don Chisholm AO
A/Prof Greg CooneyA/Prof Antony CooperProf Ted KraegenDr Ross LaybuttA/Prof Katherine SamarasDr Carsten Schmitz-Peiffer
Neuroscience
Leader Prof Herbert Herzog
Senior Scientists
Dr Sharon OleskevichA/Prof Amanda Sainsbury-SalisDr Bryce Vissel
Cancer
Leader Prof Rob Sutherland FAA
Senior Scientists
Prof Sue ClarkProf Roger DalyA/Prof Sue HenshallDr M Kohonen-CorishProf Liz MusgroveA/Prof Chris Ormandy
Cancer Development LaboratoryProf Marie Dziadek
Osteoporosis & Bone Biology
Leader Prof John Eisman AO
Senior Scientists
Prof Tuan NguyenDr Paul Baldock
Pituitary Research Unit
Leader Prof Ken Ho
Autoimmunity Research Unit
Leader Prof Fabienne Mackay
Senior Scientists
Prof Antony Basten AO FAA
Dr Robert Brink
Garvan Research FoundationBoard of Directors
Chairman Mr Graham Bradley
Garvan Research Foundation
Chief Exec Officer Ms Carole Renouf
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ORGANISATION CHART 17
Board Committees_ Business Development Advisory_ Finance & Audit_ Investment_ Remuneration
Institute Committees_ Appointments & Promotions_ BTF Policy Advisory_ Building & Equipment_ Director’s Executive_ Higher Degrees_ Information Technology_ Occupational Health & Safety_ Publications_ Seminars_ Senior Scientists
Campus Committees_ Animal Ethics_ Human Research Ethics_ Institutional Biosafety_ Precinct Management_ Precinct OH&S
Garvan is a partner in the CRCs for Asthmaand Biomedical Imaging Development.Garvan is a shareholder in the spin-outcompany G2 Therapies Ltd.
DNA samples on chipsfor epigenetic analysis.
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CANCER PROGRAM 19
CANCER PROGRAMLeader Professor Rob Sutherland FAA
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Program Overview
Although derived from normal cells, cancer cells have distinctive features that can be exploited to aid diagnosis,treatment, and prognosis. To do this, we need to know much more about the fundamental processes thatgovern cell behaviour: their division, their survival, their motility and their differentiation into complex tissuestructures. With this knowledge we will be better able to stop the formation and early growth of cancers.
As well as basic research into cell and molecular biology, the Cancer Program has six translational researchgroups that study a number of the most commonly diagnosed and most lethal cancers: breast, colorectal(bowel), lung, ovarian, pancreatic and prostate.
Program Highlights
_ Identified the anti-apoptotic protein,Bag-1, as a new molecular marker oftamoxifen sensitivity in hormone-responsive breast cancers
_ Refined and extended our models ofhow oestrogen regulates the cell cycle(cell replication or proliferation) byshowing that oestrogen regulation ofthe cell cycle gene, cyclin D1, leads toactivation of cyclin E2
_ Further defined mechanisms behind theaction of the avocado toxin persin,which acts through the endoplasmicreticulum (the region of cells wherecomplex proteins are formed) to killbreast cancer cells
_ Characterised how the activity of Gab2,a signalling protein implicated in thedevelopment of some breast cancersand certain forms of leukemia, is'switched-off' in cells
_ In collaboration with Professor SharadKumar at Adelaide's Hanson Institute,determined that a regulatory protein,Nedd4, is required for the action ofinsulin-like growth factors and hencenormal growth
_ Showed that expression of the Elf5protein is necessary for thedevelopment of breast tissue duringpregnancy and that increasedexpression of Elf5 drives mammarydevelopment and milk production innon-pregnant animals
_ Demonstrated that the cell signallingprotein, integrin-linked kinase, controlsnormal mammary gland developmentand differentiation in mice, suggestingthat altered levels of the gene may havea role in cancer progression
_ Found that mammary cancers in micecan be put into an irreversible 'sleep' stateby inhibiting the activity of the Id1 gene
_ Identified the S100A2 calcium-bindingprotein as a predictive biomarker forresponse to pancreatectomy inpancreatic cancer
_ Demonstrated that high levels of thetranscription factor Gata2 are a featureof aggressive prostate cancer and mayinfluence the action of the androgenreceptor, suggesting Gata2 may be animportant regulator of advancedprostate disease
_ Identified the MIC-1 protein as abiomarker of resistance to thechemotherapeutic drug, docetaxel, inprostate cancer
_ Showed that the developmental geneHOXA9 is methylated in almost all highgrade serous ovarian carcinomas,representing a potential new diagnosticmarker for these, the most commontype of ovarian cancer
_ Identified new prognostic biomarkers forlung cancer, in particular that concordantmethylation of the chromosome 3pgenes, DLEC1 and MLH1, is associatedwith poorer survival of patients
_ Created a human epigenome map ofnormal prostate cells and cancerprostate cells that incorporatesepigenetic modifications and geneexpression levels - allowing us toidentify novel genomic regions that are commonly deregulated in cancer
_ Demonstrated that the tumoursuppressor gene p16 is repressed (itsexpression, or conversion into proteins,reduced) before being methylated (shutdown) in cancer cells
_ Found that p16 methylation is initially'seeded' in between the nucleosomes of its promoter region (the part of thegenome that triggers the expression ofthe gene) and then spreads toconsolidate epigenetic silencing
20 CANCER PROGRAM
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_ Rebecca Hinshelwood was awarded theCancer Institute NSW 2008 Premier'sAward for Outstanding Research Scholar
_ Dr Sandra O'Toole, Dr Catriona McNeiland Haley Bennett were awarded PhDs(University of NSW)
_ Chehani Alles was awarded a Master ofScience (University of NSW), Dr RubanThanigasalam a Master of Surgery(University of Sydney), Sarah Sutherlandand Edwina Wing-Lun were awardedMBBS (Hons) (University of Sydney),and Gabrielle Matta a BMedSci (Hons)(University of NSW)
_ Professor Rob Sutherland completed a 3year term as a member of the ScientificCouncil of the International Agency forCancer Research, Lyon, and a 5 yearterm as a Board member of the CancerInstitute NSW
_ Professor Susan Clark was appointed asthe Australian representative on theAsian Epigenome Alliance, initiated andappointed Convener of the AustralianEpigenome Alliance, and continued as amember of the International HumanEpigenome Task Force
_ Cancer Program senior scientists aremembers of several major national andinternational networks: AssociateProfessor Chris Ormandy in theAustralian Phenomics Network,Associate Professor Sue Henshall andProfessor Rob Sutherland in theAustralian and Canadian Prostate CancerResearch Alliance, Professor Susan Clarkin the Alliance for Human Epigeneticsand Disease (AHEAD), and Dr MaijaKohonen-Corish in the InternationalHuman Variome Project
People Highlights
_ Six senior investigators in the CancerResearch Program (Professor Roger Daly,Professor Liz Musgrove, Professor RobSutherland, Associate Professor ChrisOrmandy, Professor James Kench andProfessor Andrew Biankin) were awardedan NHMRC Program Grant worth$11,128,320 over five years to identifymolecular markers of phenotype,therapeutic responsiveness andprognosis in human breast, prostate andpancreatic cancers
_ Professors Roger Daly and Susan Clarkwere awarded renewals of their NHMRCPrincipal Research Fellowships
_ Susan Clark and Liz Musgrove werepromoted to Conjoint Professor at theUniversity of NSW
_ Dr Alex Swarbrick received Early CareerDevelopment Fellowships from theCancer Institute NSW and the NationalBreast Cancer Foundation
_ Dr Matt Naylor received an NHMRCCareer Development Award and an EarlyCareer Development Fellowship fromthe National Breast Cancer Foundation
_ Drs Alex Swarbrick and Sandra O'Toole,in collaboration with Professor NeilWatkins at the Monash Institute ofMedical Research, were awarded anNHMRC Project Grant to study Hedgehogsignalling in breast cancer progression
_ Dr Matt Naylor was awarded researchgrants from the Cancer Council NSWand the Prostate Cancer FoundationAustralia to investigate the role ofintegrin signalling in prostate cancer andprostate development
_ Dr Pip O'Brien was awarded a priority-driven collaborative research grant fromCancer Australia to investigate DNAmethylation alterations as detectionmarkers for early stage ovarian cancer
_ Dr Alison Butt received a ResearchInnovation Grant from the CancerInstitute NSW to define novel moleculardeterminants of anti-oestrogenresistance in breast cancer and aresearch grant from Breast CancerAustralia to further develop and evaluatethe therapeutic potential of persin as ananti-cancer agent
_ Dr Alex Swarbrick, Associate ProfessorChris Ormandy, Professor Marie Dziadek,Professor Fabienne Mackay, ProfessorSam Breit (St Vincent's Centre forImmunology) and Professor MurrayNorris (Children's Cancer InstituteAustralia) were awarded a CancerInstitute NSW Equipment grant topurchase an in vivo Imaging System forlive imaging of tumour growth andmetastasis in mouse models of cancer
_ Professor Susan Clark was awarded aCancer Institute NSW Equipment grantfor purchase of a real-time cell analyserto dynamically monitor viability andproliferation of cancer cells in cell culture
Dr Toby Hulf, postdoctoralresearcher, using a Sequenommass spectrometer to analyse
the epigenetic profile ofcancer cells.
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_ Several members of the Cancer Program served on grant review panels:Professor Liz Musgrove for NHMRC,Associate Professor Chris Ormandy asChair of the NHMRC CDA ReviewCommittee, Professor Marie Dziadek forNHMRC CDA Awards and the HealthResearch Council NZ, AssociateProfessor Sue Henshall for the ProstateCancer Foundation of Australia, andProfessor Andrew Biankin for the CancerCouncil NSW
_ Senior staff members in the CancerProgram are members of 16 EditorialBoards, including Breast Cancer On-Line,Breast Cancer Research, British Journalof Cancer, Endocrine-Related Cancer,Endocrinology, Epigenomics, MolecularBiotechnology and World Journal ofGastroenterology
_ Associate Professor Chris Ormandy wasappointed Vice-Chair of the GordonResearch Conference on MammaryGland Development in 2009, and Chairof this conference in 2010
_ Professor Rob Sutherland and AssociateProfessor Chris Ormandy were membersof the Organising Committee and
Associate Professor Sue Henshall amember of the International AdvisoryGroup for the 4th PacRim Breast andProstate Cancer Meeting held inWhistler, Canada in August
_ Dr Alison Butt was appointed President-Elect and Honorary Treasurer of theAustralian Society for Medical Research,and was Convener of the 4th AustralianHealth and Medical Research Congressheld in Brisbane in November
_ Professor Susan Clark was presentedwith the WEHI Director's InauguralWomen in Science Lecture Award
_ Professor Andrew Biankin received theHirshberg Award in Pancreatic Cancerfrom the American PancreaticAssociation meeting in November
_ Cancer Program PhD students andpostdoctoral scientists received prizesfor their conference poster presentations:Brian Gloss at the Australian Society forMedical Research NSW ScientificMeeting, Maria Gonzalez at the UNSWFaculty of Medicine Research Day, andDr Toby Hulf at the 4th PacRimConference on Breast and Prostate Cancer
_ Dr Sandra O'Toole was awarded theOverall Conference Prize and Dr EwanMillar and Sarah Zardawi were givenCommendations at the AustralasianDivision of the International Academy ofPathology 33rd Annual Scientific Meeting
_ Elizabeth Shelley, Simon Junankar, DrDavid Chang and Vivienna Ong wereawarded Cancer Institute NSW ResearchScholarships and Warwick Locke wasawarded a National Breast CancerFoundation Research Scholarship
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Basic Cancer Research
Cell Cycle Group Group Leader Professor Liz Musgrove
Female steroid hormones like oestrogen and progesterone strongly influence cellreproduction in the breast. We are particularly interested in how these hormones act onthe cell cycle machinery and how control over the cell cycle is lost in breast cancer cells.Our current work concentrates on the cell cycle genes c-Myc, cyclin D1 and cyclin E2,all of which are targeted by oestrogen and are overexpressed in breast cancer. Incollaboration with the Steroid Hormone Action and Breast Cancer Translational Groupswe are searching for new genes that might link oestrogen action with the cell cycle andso could be involved in resistance of certain breast cancers to the anti-oestrogentamoxifen. We are collaborating with the Peter MacCallum Cancer Institute in Melbourneand the Diamantina Institute in Brisbane to undertake functional screens to identifygenes involved in endocrine resistance.
Steroid Hormone Action GroupGroup Leader Professor Rob Sutherland FAA
Our research aims to determine and characterise the genes that mediate the actions ofthe sex steroid hormones oestrogen, progesterone, and androgens in steroid-responsivecancers (breast, prostate, ovarian and endometrial). These constitute a third of all newlydiagnosed cancers.
In collaboration with the Cell Cycle and Apoptosis Groups we have identified and arecharacterising a number of steroid-regulated genes involved in the control of cellproliferation, cell differentiation and cell death in breast cancer. In partnership with theBreast and Prostate Cancer Groups and the Cancer Development Laboratory we havedemonstrated that some of these genes are new markers of cancer progression andresponse to therapy and candidate targets for the development of new cancer therapies.
Apoptosis Research GroupGroup Leader Dr Alison Butt
Oestrogen not only causes breast cancer cells to proliferate but it also protects themfrom apoptosis (cell death). We are investigating how this occurs and are identifying thegenes that regulate this process. Such studies will enable us to understand how thesegenes may influence the way anti-oestrogens such as tamoxifen can effectively killbreast cancer cells. In other projects we are examining how novel compounds derivedfrom plants induce apoptosis in breast cancer cells. This could lead to their developmentas new therapies for the treatment of breast cancer as well as other cancers.
Signal Transduction GroupGroup Leader Professor Roger Daly
Our research focuses on how signals regulating biological processes such as cellproliferation, survival and motility are transmitted within the cell, and how these signalsare altered in cancer cells. We have determined that the activity of a key signalling
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protein, Gab2, is regulated by a class of binding proteins termed 14-3-3 that 'switch-off' Gab2 and prevent it from transmitting signals within the cell. We have identifiedthat Gab2 promotes cell motility as well as cell proliferation, and demonstrated that it ishighly expressed at very early stages of breast cancer development. In other studies wehave made important discoveries regarding the regulatory mechanisms inside the cellthat modulate the action of insulin and insulin-like growth factors, with implications forthe control of animal metabolism and growth. Finally, we have established newmethodologies to characterise global alterations in protein phosphorylation associatedwith cellular signalling events, and are applying these to the identification of noveltherapeutic targets and prognostic markers in cancers refractory to current treatmentregimens, such as basal-type breast cancers.
Epigenetics GroupGroup Leader Professor Susan Clark
Cancer cells can modify the expression of critical cancer genes independently of theDNA sequence, using two epigenetic biochemical processes called DNA methylation andhistone modification. Our research focuses on understanding the mechanism thattriggers abnormal methylation and histone modification between normal and cancercells. We have developed different methods to detect methylation changes during earlycancer development and have discovered that these epigenetic changes can take placenot only in single genes, but can also occur across very large regions of DNA during thespread of cancer. These changes provide novel tumour "signatures" for cancer diagnosisas well as potential targets for cancer therapy. We are now trying to determine whichchanges are specific to breast and prostate cancer and the sequence of events thattrigger these changes so that we can try to reverse the process. This is a large andcomplex project and our work forms part of the international effort on unravelling thehuman epigenome.
Development GroupGroup Leader Associate Professor Chris Ormandy
Development of the mammary gland occurs in defined stages that are governed by thehormones that regulate reproductive events. We hypothesise that genes controllingnormal mammary development can become mutated or deregulated in breast cancerand thus contribute to the disease process. We have discovered that the transcriptionfactor Elf5 controls the development of the mammary gland during pregnancy and alsoregulates the proliferation and function of breast cancer cells. We are investigating howElf5 exerts these effects to provide a way to therapeutically target this mechanism.
Tumour Progression GroupGroup Leader Dr Alex Swarbrick
Most aggressive cancers have two features in common: they proliferate endlessly (havehigh self renewal) and contain mostly unspecialised, poorly differentiated cells. We areinvestigating genes that control self renewal and differentiation in cancer, with aparticular focus on breast cancer. Together with the Breast Cancer Translational Groupand external collaborators we have discovered that several genes are key controllers ofthe growth and metastasis (spread) of poorly differentiated cancers. These include thetranscriptional regulator Id1, the Hedgehog signalling protein, and also the non-codingmicroRNA-380. Understanding the contribution of these genes to cancer progressionwill help us predict the behaviour of aggressive metastatic cancers and may ultimatelylead to the development of new drugs to stop their growth.
Integrin and Cell Biology GroupGroup Leader Dr Matthew Naylor
Our research aims to understand the mechanisms that regulate cell fate decisions duringthe progression of cancer to metastatic disease. Integrins mediate the adhesion of cellsto the extracellular matrix and provide cells with a positional identity in addition tocoordinating growth factor and hormone signalling to control cell function. Modulationof integrin expression and function can alter the cancer phenotype. We are currentlyinvestigating integrin function during mammary and prostate gland development and inexperimental models of carcinogenesis and metastasis. We are also investigating the roleof several cell fate transcriptional regulators during mammary gland development,cancer and metastasis.
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Translational Cancer Research
Breast CancerGroup Leader Professor Rob Sutherland FAA
In association with clinicians at St Vincent's and other hospitals in Sydney we havedeveloped large tissue banks and patient databases that are being used to identifymarkers of disease subtype, disease progression and response to particular therapies. Amajor joint project with the Cell Cycle and Steroid Hormone Action Groups is identifyingmolecular markers of tamoxifen resistance, since loss of response to tamoxifen is amajor reason for treatment failure. We are also conducting collaborative studies in-house and with other institutions to define the role of newly-discovered breast cancergenes in the disease process.
Lung and Colorectal CancerGroup Leader Dr Maija Kohonen-Corish
Our area of expertise is colorectal and lung cancer genetics and epigenetics. We examinethe gene profiles of resected tumour tissues and correlate them with patient clinicaloutcomes. The challenge is to work out which key gene alterations and biomarkers arethe most useful for determining prognosis and treatment outcomes, in order to improvethe clinical management of patients. We have identified new genes that are inactivatedthrough epigenetic mechanisms in cancer. In lung cancer we have analysed genes onchromosome 3p, an area of the genome important in lung cancer development. Wehave shown that aberrant methylation may be synchronized in this region and that thepresence of this defect in the cancer is associated with poor patient prognosis.
Dr Warren Kaplan,bioinformatics specialist at
Garvan's Peter WillsBioinformatics Centre,
discusses gene expressionprofiles (obtained frommicroarray chips) with
Dr Toby Hulf.
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Ovarian CancerGroup Leader Dr Philippa O'Brien
Our group works in collaboration with the Gynaecological Cancer Centre at the RoyalHospital for Women. Our major research goal is to use our combined expertise andknowledge to identify new ways to diagnose women with early stage curable ovariancancer. To this end we utilise a number of different approaches to identify the genesinvolved in the development of ovarian cancer, particularly its early stages. Our primaryfocus is the identification of genes with altered methylation patterns that have potentialas blood-based diagnostic markers for early stage ovarian cancer. We also aim tounderstand how such genes influence ovarian cancer development, which mayadditionally identify new treatment targets for women with advanced disease.
Prostate CancerGroup Leader Associate Professor Sue Henshall
Our group is concerned with the identification of markers for therapeuticresponsiveness, prognostic markers, and new markers of early prostate disease. We takea multidisciplinary approach that utilises expertise from a number of cancer researcherswithin and outside the Garvan, as well as clinicians and pathologists. We aim to identifygenes and pathways whose expression changes can predict the development ofaggressive life-threatening prostate cancer or resistance to chemotherapy used for thetreatment of advanced stage prostate cancer.
Pancreatic CancerGroup Leader Professor Andrew Biankin
Pancreatic cancer is the fifth leading cause of cancer death in Western societies, with afive year survival rate of less than 10%. The treatment and survival of patients withpancreatic cancer has not changed for over thirty years because there has been littleresearch into the molecular and cell biology associated with it. Our projects focus onimproving outcomes for patients by using biomarkers to guide therapeutic decisions topersonalise therapies for pancreatic cancer. In addition, we are investigating molecularmechanisms of pancreatic carcinogenesis which may lead to the development of noveltherapeutic strategies.
Cancer Therapeutics Development Laboratory
Research Director Professor Marie Dziadek
The Cancer Therapeutics Development Laboratory is investigating the potential fordeveloping cancer therapeutic drugs against molecular targets expressed by cancer cells.Our current project aims to block the activity of a key enzyme that is highly expressedin many different types of cancer. This enzyme allows cancer cells to produce theenergy that is essential for their growth. We developed and completed a highthroughput screen (HTS) of a chemical library in collaboration with the WEHI/Bio21 HTSfacility in Melbourne. This screen identified a number of potent inhibitor compounds thatwill now be evaluated for their efficacy in blocking cancer cell growth. We will determinewhich of these compounds will form the best lead for further drug development.
2D gel showingproteins in mouse liver.
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DIABETES & OBESITY PROGRAMLeader Professor David James FAA
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Program Highlights
_ Demonstrated that the cellular stressresponse known as ER stress (adisruption of the cell's ability to createproteins) is not a major contributor tothe death of insulin-secreting pancreaticcells in Type 1 diabetes, whereas it playsa significant role in Type 2 diabetes
_ Improved insulin resistance of rodentsfed a high fat diet by manipulating thelevels of one key metabolic enzyme inleg muscle
_ Showed that weight reduction in morbidlyobese people with Type 2 diabetesreduces inflammation, which may beimportant in reducing insulin resistance
_ Isolated four promising bioactivecompounds in bitter melon, a vegetableand traditional Chinese medicine, helpingus understand its potential for treatingType 2 diabetes
_ Found that healthy weight, insulin-sensitive, relatives of people with Type2 diabetes secrete less of an appetite-curbing gut hormone after meals thanthose without diabetes in the family,making them more prone to gain weightlater in life
_ Uncovered mechanisms, involving pro-inflammatory molecules, that may helpexplain why people being treated forHIV infection have high rates of diabetesand heart disease, similar to those whoare very overweight and insulin resistant
_ Showed that insulin regulates glucoseentry into cells by activating a motorprotein, known as myo1c, that helpsmove glucose transporters to the cellsurface
_ Reported novel insights into the intricatecell signalling mechanisms behind insulinresistance, a risk factor for Type 2diabetes, in particular reviewing theimportance of a molecule known asIRS1, previously thought to be critical
Program Overview
The growing incidence of obesity is driving a worldwide epidemic in Type 2 diabetes, a disease which alreadyaffects nearly 1 in 10 of the Australian population. Research in this program is focused on the molecularregulation of body weight and fuel metabolism, and obtaining a better understanding of Type 2 diabetes atmultiple levels. There is a particular emphasis both on the release of insulin and its mode of action in normal anddisease states. Research strengths include live cell microscopy, the use of mass spectrometry for the discoveryof new molecules affected by metabolic disease, in vivo gene manipulation and metabolic studies in humans.
Our basic and clinical research efforts are closely linked. We ask ourselves the major questions about whydiabetes develops and what other factors, including dietary and genetic, might be involved. Many of ourstudies focus on humans with a genetic risk for diabetes in an effort to identify factors that occur very early inthe onset of the disease. Such studies have begun to identify blood factors that may be released from immunecells or blood vessels and are examining key differences in fat from different parts of the body.
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People Highlights
_ The Diabetes and Obesity Program wasawarded an NHMRC program grantworth $10.5 million over 5 years
_ Professor David James was invited togive the 2008 Novo NordiskInternational Lectureship at theUniversity of Toronto
_ Dr Kyle Hoehn was awarded the 2009Viertel Fellowship from the DiabetesAustralia Research Trust (DART)
_ Dr Jiming Ye, Dr Bronwyn Hegarty,Professor David James, Dr JerryGreenfield, Dr Carsten Schmitz-Peifferand Associate Professor Trevor Bidenwere awarded NHMRC project grants
_ Dr Katy Raddatz was awarded a GermanResearch Foundation (DFG) Post-Doctoral Fellowship
_ Amanda Preston and James Burchfieldsuccessfully obtained their PhD degrees
_ Associate Professor Katherine Samaraswas invited to participate in theAustralian Academy of Science's TheoMurphy High Flyers Think Tank and alsothe National Preventive HealthcareSummit for the National PreventativeHealth Taskforce, “Curbing the ObesityEpidemic: the role of the individual andthe role of the State”
_ Professor Lesley Campbell was an invitedplenary speaker at the IASO StockConference in March 2008 on "Hormonesand Obesity"; as well as at an InternationalSymposium on Obesity at the Instituteof Preventative Medicine in Copenhagen.
_ Dr Alex Viardot was awarded the inauguralDon Chisholm Fellowship for 2009
Research Groups
Appetite and Adiposity in Pre-diabetes and Prader Willi SyndromeGroup Leader Professor Lesley Campbell AM
Our group studies the basic abnormalities in metabolism in people with disorders ofprediabetes and obesity. One major focus is the study of a genetic disorder that occursfrequently in young children, known as Prader Willi Syndrome (PWS). This disorder iscommonly associated with lower lean body mass, and with relentless childhood weightgain, and so is of great interest in our understanding of the genetics of human bodycomposition. These studies, in collaboration with Royal Prince Alfred Hospital andProfessor Herbert Herzog's laboratory (Garvan Neuroscience), compare hormonal andmetabolic differences to matched obese subjects as well as testing potential therapeuticoptions. Studies are underway to prepare a novel mouse model of PWS based on a veryrecent genetic discovery about the nature of PWS genes. A second major focus of ourgroup is identification of the factors that predispose individuals to Type 2 diabetes.These studies have revealed a predisposition to eat more (low levels of PYY hormone),an increased innate immune and T cell activation (better at fighting primitive organismsbut more tendency to inflammation and possibly atheroma) and a more active "fight andflight" response (but also more central fat, more hypertension and metabolic syndrome).
Fat and Insulin Resistance Group Leader Professor Don Chisholm AO
We have been studying patients with hepatitis C because of their predisposition toinsulin resistance and Type 2 diabetes. We have shown that the insulin resistance ispresent in muscle rather than in liver, contrary to common belief. We have also identifiedfor the first time an elevation in glucagon in these patients, which may also contributeto Type 2 diabetes. The group continues their work on abdominal obesity and, incollaboration with the Cell Biology group, is undertaking studies of adipose tissuetransplantation in mice.
Molecular MetabolismGroup Leader Associate Professor Greg Cooney
Fat accumulation causes problems with metabolism that can lead to Type 2 diabetes,heart disease and stroke. The major focus of the Cooney group is to understand factors(genetic and environmental) that control fat accumulation in muscle and liver and to usethis information to devise strategies to reduce fat. When fat enters a cell from bloodthere are two major choices for its fate. It is either stored as an intracellular lipid or it ischannelled into the mitochondria, where it is burned for energy. We are studying theregulation of glucose and fatty acid metabolism by mitochondria and the changes thatoccur in normal metabolic cycles when tissues are exposed to too much fat at differenttimes of the day. This could help explain the contribution of increased food availabilityand altered eating habits to the rapid increase in obesity and metabolic disease.
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ER Stress and Protein MisfoldingGroup Leader Associate Professor Antony Cooper
Our group aims to understand how cells cope, or fail to cope, with the stress that canresult from the over-production of proteins and misfolding of proteins within a cellularcompartment called the endoplasmic reticulum (ER). ER stress is directly applicable to agrowing number of diseases including diabetes, as well as many diseases of the brain likeHuntington's, Parkinson's, Alzheimer's and motor neuron disease. Either the cell 'burnsout', generates an excess of harmful products, or accumulates unmanageable amountsof unusable proteins, which ultimately lead to cell death. If the mechanism by whichthese stressors induce cell death can be elucidated, this may enable identification ofpotential points of intervention to help cells deal with extra demands.
Human PhysiologyGroup Leader Dr Jerry Greenfield
In collaboration with the Cell Biology group, we are undertaking a major study toidentify defects in insulin signal transduction in skeletal muscle from at-risk individuals.We are also examining the possible role of the autonomic nervous system in thedevelopment of diabetes and obesity. Studies have also been established examining theeffects of glutamine, an amino acid, on metabolism, both in isolation and in combinationwith a new diabetes medication. Glutamine appears to have a promising effect onglucose lowering in the post-meal state and may offer a simple, novel and effectivetreatment in Type 2 diabetes.
Dr Ross Laybutt, head of theIslet Biology Group, andpostdoctoral researcher
Dr Katy Raddatz discuss levelsof particular proteins
(molecules), as shown on a2D gel.
Phospholipid BiologyGroup Leader Dr Will Hughes
Phospholipids are the basic building blocks of cell membranes but, as is becomingclearer, some are also dynamically regulated to enable control of many of the majorfunctions of cells. Two such examples are the stimulated secretion of insulin frompancreatic beta cells after a meal, and the movement of glucose transporter GLUT4 tothe plasma membrane in muscle cells to allow glucose uptake in response to insulin. Wecontinue to use state-of-the-art live cell microscopy to see where and when inindividual cells the dynamic changes in phospholipids occur to determine how they mayregulate insulin release or GLUT4 movement. In collaboration with the Cell Biology andMolecular Metabolism groups, we aim to identify precisely which intracellular processesmay be defective in diabetes.
Cell BiologyGroup Leader Professor David James FAA
A major action of insulin that becomes defective in Type 2 diabetes is the regulatedentry of nutrients into muscle and fat cells. The goal of our group is to use newlydeveloped molecular imaging methods to study the insulin-regulated movement of theGLUT4 glucose transporter as well as other processes in insulin responsive cell types.Also using mass spectrometry, novel molecules involved in insulin action have beenidentified and these represent the focus of many future studies. These studies dovetailwith a major investigation into the mechanism of insulin resistance in muscle and fat,with recent studies from the group highlighting an important role for oxidative stress.
Diabetes and MetabolismGroup Leader Professor Edward Kraegen
Understanding how too much fat causes insulin resistance in muscle and liver is themajor thrust of our work. Various experimental models and state-of-the-art techniquesare being used to identify and manipulate key proteins in muscle that link fat metabolismto insulin action. Important pathways under investigation are those activated by thenewly discovered hormone adiponectin and involving the enzyme AMP-kinase. Studiesusing traditional Chinese medicines with collaborators in Shanghai to identify newinsulin-sensitising agents that could be more useful than current therapeutics are alsounderway. Excitingly, some of these molecules modulate AMP-kinase, a majorintracellular regulator of cellular energy status. Work is also ongoing in partnership withpharmaceutical companies to identify ways of reducing fat accumulation by influencingthe rate of entry of fatty acids into mitochondria for oxidation.
Obesity in Diabetes and Diabetes and HIVGroup Leader Professor Katherine Samaras
Obesity is the major accelerating factor in the pathogenesis of Type 2 diabetes inhumans. We have been studying the progress of obese diabetic patients in response toweight loss regimens, finding 60% will normalise glucose tolerance within 12 weeksafter bariatric surgery. Early results show these rapid improvements in diabetes are notexplained by weight loss, but associated with immune system changes. This workcontinues to dissect the role of circulatory and tissue-based inflammation in response toweight change, thus providing valuable insights into pathogenesis and potentialtherapeutic targets for treating the commonest form of diabetes. Work in people livingwith HIV infection, in collaboration with St Vincent's Hospital and the National Centre forHIV Epidemiology and Clinical Research, showed treatment-induced metabolicsyndrome, predicting subsequent premature development of Type 2 diabetes and heartdisease. Studies of how these drugs affect glucose and lipid metabolism and vascularfunction are now underway. In particular, patients are being followed over a 10 yearperiod, in one of the longest longitudinal cohorts internationally.
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Diabetes Signalling Unit
Beta Cell SignallingGroup Leader Associate Professor Trevor Biden
Identifying and preventing the cellular mechanisms whereby fatty acids disrupt beta cellfunction is one of our major goals. These processes are fundamental to the progressionof Type 2 diabetes, yet are poorly understood. We are piecing together the mechanismof action of protein kinase C epsilon (PKCe), an enzyme they found to be a keydeterminant of defective insulin secretion. Studies are underway to identify inhibitors ofthis enzyme as a possible future therapy for Type 2 diabetes. Another major project isexamining the molecular links between fatty acids and beta cell death, with particularemphasis on ER stress. Most notably, with colleagues in the Islet biology group, we haverecently shown for the first time that ER stress occurs in beta cells of human subjectswith Type 2 diabetes.
Islet BiologyGroup Leader Dr Ross Laybutt
Pancreatic beta-cell failure is fundamental to the development of diabetes. Our goal isto identify mechanisms responsible for the beta-cell destruction and the loss of insulinsecretion that cause diabetes. The major hypothesis under investigation is that in Type 2diabetes a gradual rise in blood glucose (hyperglycaemia) and lipid levels leads to a lossof the unique expression pattern of genes necessary for appropriate insulin secretion.This worsens hyperglycaemia, which causes further beta-cell dedifferentiation andeventually beta-cell death. In models of Type 1 diabetes, investigations into the role ofendoplasmic reticulum (ER) stress as a mechanism responsible for beta-cell destructionare being conducted. Recent work from our group argues against a role for ER stress asa mechanism for beta-cell destruction in Type 1 diabetes, in contrast to the situation inType 2 diabetes.
Insulin SignallingGroup Leader Dr Carsten Schmitz-Peiffer
We focus on the lipid metabolites that disrupt insulin signaling and how these contributeto insulin resistance. A new study area has been initiated by the discovery that di-linoleoyl phosphatidic acid is an important inhibitor of insulin signaling. In collaborationwith industry partners, studies to block production of this metabolite are in progressfollowed by verification in human subjects. Another focus of our group is kinase C epsilon(PKCe), which exerts action on liver to decrease whole-body availability of insulin. This,in addition to its actions in beta cells, constitutes a second reason for inhibiting PKCe, asa potential therapy for Type 2 diabetes. In addition, a proteomics approach is being usedto understand the mechanisms through which blocking of the lipid-activated inhibitorymolecule PKCe improves glucose metabolism in insulin target tissues.
Decanting medium offadherent spleen cells.
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IMMUNOLOGY & INFLAMMATION PROGRAMLeader Professor Charles Mackay FAA
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Program Overview
Our researchers study aspects of immune function in normal anddiseased situations. We hope to understand the basis for diseases suchas rheumatoid arthritis, autoimmune diseases, diabetes and asthma, andalso to develop new therapies to treat disease. We also collaborate withGarvan scientists in other programs on cross-discipline projects such asfinding links between immunology and metabolic systems, cancer andthe nervous system.
Program Highlights
_ Showed that T follicular helper cells (acertain class of immune cell), which playa key role in triggering the production ofantibodies, need the molecule IL-21both to survive and to function
_ Identified the basic biochemistry andstructural features of IL-21, a keyregulatory molecule of the immunesystem, with the aim of developing newdrugs to treat certain cancers andautoimmune diseases
_ Elucidated the molecular mechanismsbehind the action of Stat3, a gene thatworks in all immune cell types to helpkeep fungal and bacterial infections at bay
_ Human trials began in Europe of anantibody we developed to block C5aR -a molecule implicated in inflammatoryconditions such as rheumatoid arthritis,autoimmune diseases, eye diseases and sepsis
_ Established in mice that the cytokineGM-CSF, which has many differentactions in various immune andinflammatory responses, plays animportant role in asthmatic airwayinflammation
_ In collaboration with the CRC forasthma, developed a therapeuticantibody against GM-CSF
_ Identified CXCR7 as a gene for heartdevelopment
_ Identified IL-21 as an inducer of theproduction of IgE by B cells. IgE isresponsible for many of the symptomsof allergy. This represented a novelunderstanding of the way IgE productionis regulated
_ Characterised the basic biochemistryand structural features of IL-21, a keyregulatory molecule of the immunesystem, with the aim of developing newdrugs to treat certain cancers andautoimmune diseases
_ Demonstrated that raised levels ofimmunoregulatory CD4+ T cells caninduce long-term acceptance ofpancreatic islet allografts withoutimmunosuppression
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_ Helen McGuire received the followingawards: St Vincents & Mater HealthResearch Symposium Award for Excellencein Oral Presentation; ASI travel bursaryto FIMSA Taiwan conference; and CastleHarlan Award - most outstanding earlycareer PhD student
_ Professor Jonathan Sprent gave invitedpresentations in Davos and Lausanne inSwitzerland, Florence in Italy, Tokyo andTokushima in Japan, and Havana in Cubaas well as meetings in Melbourne,Brisbane and Canberra
_ Dr Di Yu was invited to the followingconferences: The 10th InternationalWorkshop on Auto-antibodies andAutoimmunity, Mexico and the AmericanCollege of Rheumatology AnnualScientific Meeting, San Francisco, TheUnited States. He was also awarded aC.J. Martin Fellowship
_ Dr Jenny Gunton was an invited speakerat the Endocrine Society of Australia/Australian Academy of Science rising starsymposium; an invited speaker at theEndocrine Society of Australia ClinicalSymposium weekend, is honorarysecretary of the Australian DiabetesSociety and is the chair of the programorganising committee for the ADS annualscientific meeting. She was awarded aJDRF ITP research grant and a a DiabetesAustralia Research Trust grant
_ Professor William Sewell was an invitedspeaker at the Australian DermatologyUpdate Symposium in Sydney and theFrontiers in OtorhinolaryngologyConference in Noosa
_ Dr Sue Lynn Lau won the dance yourPhD competition, and was awarded a aDiabetes Australia Research Trust grant
People Highlights
_ Sandra Gardam was invited to present at the annual scientific meeting of theRussian Society of Immunology held inSt Petersburg. Sandra was awarded anNHMRC Training Fellowship - OverseasBased Biomedical Fellowship
_ Alexis Vogelzang was awarded NewInvestigator of the Year at the annualscientific meeting of the AustralasianSociety of Immunology held in Canberra
_ Dr Daniel Christ was an invited speakerat the following meetings: the annualProtein Engineering Summit (Boston),CBSM (Perth) and at researchinstitutions and companies (Monash,CSL). He was awarded a CDA Fellowshipfrom the National Health and MedicalResearch Council (NHMRC)
_ Kip Dudgeon received a postgraduatescholarship from the NHMRC
_ Dr Tri Phan, NHMRC CJ Martin Fellowfrom UCSF, returned to Garvan in Dr Rob Brink's laboratory. Tri was previouslyworking with Dr Jason Cyster on 2Photon Microscopy
_ Kylie Webster won a St Vincent'sResearch Symposium Award for OralPresentation and a TSANZ (TransplantSociety of Australia and New Zealand)Young Investigator Award
_ Emeritus Professor Antony Basten wasan invited speaker at the followingmeetings: The Kunkel Society annualmeeting on autoimmunity (SantaMargherita, Italy), International B cellWorkshop on vaccination (Oxford, UK)and the 12th Australasian AutoimmunityWorkshop( Sydney)
_ Dr Stuart Tangye was invited to presentseminars at conferences held in NewZealand, Brisbane, New York, and atresearch institutes in Bethesda (NIH),Melbourne (WEHI), New York(Rockefeller University), and California(DNAX Research Institute)
_ Kendle Maslowski received an NH&MRCPhD Scholarship and received thefollowing awards: Transplant Society ofAustralia and New Zealand (TSANZ)Travel Grant; Best Presentation Award,TSANZ ASM (for best oral presentationin the Cell Biology SIG); AustralianSociety for Immunology travel grant. He gave Oral presentations at the 2ndWorld Immune Regulation Meeting,Davos Switzerland; the Thoracic Societyof Australia and New Zealand AnnualScientific Meeting in Melbourne; and theAustralian Society for Medical Research,N.S.W. branch
_ Stacey Walters received a NovartisYoung Investigator Travel Award;Transplant Society of Australia and NewZealand (TSANZ) New Key OpinionLeader Best Abstract Award; TSANZPresident's Prize Award; and St. Vincent'sSymposium Poster Prize
_ Stacey Walters, Rebecca Stokes, KylieWebster and David Liuwantara receiveda Transplant Society of Australia andNew Zealand Young Investigator Award
_ Alexis Vogelzang, Helen McGuire andSanti Suriyani received an ASI Travel Awardas well as FIMSA travel bursary to Taiwan
_ Dr Sue Mei Lau received the NovartisJunior Scientist Prize at the EndocrineSociety of Australia Annual Meeting anda Diabetes Australia Research Trust grant.
_ David Liuwantara received a MerckCompany Foundation Fellowship
_ Dr Cecile King was invited speaker at the Australasian Diabetes Society AnnualMeeting. CK received an Innovativegrant from the Juvenile DiabetesResearch Foundation and an NHMRCproject grant
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Research Groups
Immunology and InflammationGroup Leader Professor Charles Mackay FAA
Immunology lies at the heart of many human diseases. Poor immune responses can leadto the development of cancers or infections. Over-zealous immune responses lead toallergies, or autoimmune diseases such as Type 1 diabetes, rheumatoid arthritis andmultiple sclerosis. We are trying to understand all of the cellular and molecular processesof immune responses, and what goes wrong to cause disease. Increasingly, we arediscovering integral connections between the immune system and the metabolicsystem, the nervous system and cancer. One important activity of our program hasbeen to translate discoveries into new treatments that will impact on the health ofmankind. Our studies have led to development of antibodies that can intervene in theinflammatory process and these are being developed by Garvan spin-off G2 TherapiesLtd. We are studying the link between diet, fatty acid binding proteins and asthma; andlooking more broadly at the links between inflammatory and metabolic diseases becausewe now know that inflammatory cells release factors that can affect various aspects ofmetabolism. We are also exploring a new hypothesis that gut microbes, and our diet,determine the nature of inflammatory responses.
Asthma Group Leader Dr David Zahra**Part of the CRC for Asthma and Airways
Our group focuses on the development of a promising therapeutic that neutralises thefunction of the cytokine GM-CSF. GM-CSF has been linked to a number ofinflammatory diseases including asthma and rheumatoid arthritis, and we havedeveloped an antibody that blocks GM-CSF. This antibody has been successfully'humanised' and the epitope that our antibody binds on GM-CSF has been defined. Thepotential therapeutic is protected by two provisional patents and is now ready for pre-clinical and toxicology studies. A feasibility study is being conducted in collaboration witha major pharmaceutical company with the aim of fully licensing the therapeutic for pre-clinical and clinical development by the end of 2009.
Dr Cecile King, head of theMucosal Immunity Group,
with PhD student HelenMcGuire using a Magnetic
Activated Cell Sorter (MACS).The MACS uses magnetic
beads coated with antibodyto bind to surface molecules
on cells of interest - in thiscase purifying T cells (white
blood cells) from spleen cells. Dr King's lab studies a subset
of T cells (T follicular helpercells) which direct antibody
production in the lymphnodes and spleen.
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Cellular ImmunityGroup Leader Professor Jonathan Sprent FRS FAA
Our team is interested in the development and fate of T cells - white blood cells thatparticipate in a variety of immune responses but are able to somehow distinguishbetween self and foreign antigens. One of the unknown questions that is central tomaintaining the immune system's homeostasis is how are these cells destroyed oncetheir mission is complete and infections are overcome? We know that most self-destruct and a few live on to become memory T cells, which are activated by a re-infection, but we don't know the factors that determine their destiny. Application of ourwork lies in harnessing the immune system to boost its attack on cancerous tumoursand, conversely, dampening down the immune response to treat autoimmune diseases.
Diabetes and Transcription FactorsGroup Leader Dr Jenny Gunton
The causes of beta-cell failure are not well understood, but we know there are changesin these cells' gene expression that can yield clues about what is going wrong. Throughthe use of a variety of tissue-specific knockout and transgenic mice we hope to identifywhy beta cell failure occurs as well as ways to improve beta cell function and therebytreat human diabetes. We are currently focusing on a gene called ARNT, which isdecreased by 90% in the beta cell containing islets of people with Type 2 diabetes. Itseems to be a master gene that controls other genes involved in beta-cell function,including glucose breakdown and insulin production. We are now looking at ways tocontrol ARNT.
Gene Therapy & AutoimmunityGroup Leader Dr Shane Grey
Our laboratory is interested in the how and why of the immune system's attack on the body's tissues as it occurs during the rejection of organ grafts and in autoimmunedisorders like Type 1 diabetes where the insulin-producing beta cells are destroyed.Approaches include examining factors that regulate the immune attack on our own cells and investigating the molecular changes that occur in the tissue being attacked inthe hope of, one day, being able to genetically engineer tissues that could withstand the assault. This strategy would alleviate the need for the toxic immunosuppressivedrugs currently required to promote successful organ transplantation and, in the case of Type 1 diabetes, enable creation of a 'death-defying' beta cell as a novel cure.
ImmunobiologyGroup Leader Dr Stuart Tangye
Our focus is on understanding the development of B cells - the population of whiteblood cells responsible for the production of protective antibodies - and the regulationof antibody responses. We are particularly interested in understanding how the immunesystem responds to infections or vaccinations by providing us with a 'memory' of theresponse so that we cope faster and better with subsequent exposure from the sameinfectious agent. The development of immunological memory involves interactionsbetween B cells and 'helper' T cells - another subset of immune cells. Thus, a majorfocus of our work is to understand exactly how helper T cells instruct B cells to produceantibodies. We also study several genetic conditions of the immune system, andcorresponding mouse models, that result in immunodeficiencies - disorders wherebyaffected individuals are unable to mount appropriate immune responses followingexposure to some infections or pathogens. These diseases include X-linkedlymphoproliferative disease, common variable immunodeficiency and hyper-IgEsyndrome. Overall, we hope to identify means to improve the immune response inindividuals with immunodeficiencies and, conversely, ways in which the immune systemof patients with autoimmune diseases could be attenuated.
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Mucosal AutoimmunityGroup Leader Dr Cecile King
In Type 1 diabetes, the insulin-producing beta cells of the pancreas are destroyed byself tissue-destructive T cells. These cells express markers that help us to determine,for example, their dependence upon growth factors and where they have been in thebody. We are particularly interested in the relationship between the cells that causeType 1 diabetes and other autoimmune diseases that develop at the mucosal interfacebetween our bodies and the environment. Broad-based immunosuppression iscommonly used to treat autoimmune diseases and transplant recipients but it has anobvious drawback since we need a functioning immune system in order to thrive. Theaim of our research is to identify target molecules for selective suppression of theseself-tissue-destructive cells.
Antibody Engineering Group Leader Dr Daniel Christ
Our laboratory is working on the development of novel antibody therapeutics. Inparticular, we are interested in the engineering of human antibody fragments, whichare considerably smaller than current monoclonal antibodies. Human antibodyfragments (such as domain antibodies) can be generated by genetic engineeringtechnology, completely bypassing the use of animals. These fragments can beproduced in large quantities in bacteria and open up promising new routes for non-intravenous applications, imaging and therapy. We are applying our technology totargets in cancer and inflammatory diseases.
Spinal X-ray with fractures.
_ Participated in the first multi-nationgenome-wide search to find geneslinked to osteoporosis and fracture,resulting in the identification of severalchromosomal regions that could harbournovel osteoporosis-risk genes
_ Showed, by combining our own studywith studies by other research groups,that individuals with specific variants ofa major bone regulating gene are atincreased risk of reduced bone mass andfracture, information which can beincluded in fracture risk calculation
_ Demonstrated, through a study on morethan 600 men, that those with levels oftestosterone below specific levels are atgreater risk of fracture
_ Demonstrated that men with prostatecancer, particularly those who receivedandrogen deprivation therapy, had anincreased fracture risk
_ Used a Bayesian (statistical) method toestimate the probability of sport doping;based on certain blood hormone levels(a collaborative study with colleaguesfrom Garvan's Pituitary Research Unit)
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OSTEOPOROSIS AND BONE BIOLOGY PROGRAM 39
OSTEOPOROSIS & BONE BIOLOGY PROGRAMLeader Professor John A Eisman AO
IIIIIIIII IIII
Program Highlights
_ Data from the Dubbo OsteoporosisEpidemiology Study demonstrated theassociation between fragility fractureand premature mortality in both menand women for all types of osteoporoticfractures
_ Developed prognostic models forpredicting an individual's fracture riskand incorporated them into a web-basedcalculator, atwww.fractureriskcalculator.com, used bydoctors and patients worldwide
_ Collaborated with several majorinternational and national research teamsall seeking to validate and use our riskcalculator in their data
_ Demonstrated the central (brain) controlof bone cell function, the relief (orreduction) of which leads to a doublingof bone volume
_ Further characterised the neuralsignalling pathway in bone that allowsthe brain to control bone mass andstrength (a collaborative project with theGarvan Neuroscience Program)
Program Overview
Osteoporosis affects older men and women. It brings with it major coststo the individual and community, serious impacts on being able to liveproductively and also premature mortality. As prevention is the beststrategy for reducing this large human and financial burden, we need toimprove our knowledge of the risk factors from fracture; find ways tobetter assess treatments; increase our understanding of bone biology;and help identify new treatment possibilities.
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Montreal, Canada. She was alsoawarded a Novo Nordisk clinical grantexamining effects of vitamin D
_ Dr Paul Baldock was invited to join areview panel for NHMRC Project Grants,and to present to the Kings Cross RotaryClub, following from their Excellence inWorkmanship Award. He was awarded atravel grant from the International Boneand Mineral Society to present at theexclusive Davos Workshop: BoneBiology & Therapeutics in Switzerland;invited to present at a Symposium tothe Australasian PaediatricEndocrinologist Group (APEG) AnnualMeeting in Broome and to give aSymposium Presentation at the 2008European Society for ClinicalInvestigation. He has been invited topresent in the opening symposium atthe 2009 annual conference of theAmerican Society of Bone and MineralResearch in Denver Colorado
_ Osteoporosis and Bone Biology programstudents successes include: Steve Frostgiven best presentation award, UNSWStudent Conference; Bich Tran awardeda Solander Program scholarship forcollaborative work with Lund University,Sweden and a Harvey Carey MemorialTrust Scholarship; Ayse Zengin awardedan APA Scholarship; Iris Wong and BichTran awarded travel grants to attend theAustralian and New Zealand Bone andMineral Society Meeting, Melbourneand Bich Tran a UNSW travelling grant to attend the ASBMR Scientific Meetingin Montréal
_ Dr Nina Emaus from Norway joined theEpidemiology group for six months andDr Frank Driessler from Berlin joined theBaldock Group
People Highlights
_ Professor John Eisman chaired thedevelopment group for Guidelines forOsteoporosis Management supported bythe Federal Department of Healththrough the Royal Australian College ofGeneral Practitioners. He was invited asa key opinion leader to the Departmentof Health and Ageing funded Quality Useof Medicines (QUM) in Osteoporosis,Osteoarthritis and Rheumatoid Arthritis(QUM OPORA) Workshops in Sydney(November 2007). He is chair of theLocal Organising Committee for theInternational Bone and Mineral Societyto meet in Sydney in 2009
_ Professor Tuan Nguyen was promoted tofull Professor at the University of NewSouth Wales and was awarded a SeniorResearch Fellowship by the NationalHealth and Medical Research Council. Hesuccessfully convened the internationalosteoporosis meeting Strong Bone Asiain Ho Chi Minh City, Vietnam, whichattracted 500 participants from Asiaand Pacific region. He was also invited topresent his work in 3 symposia onosteoporosis in Hanoi, Ho Chi Minh City,and Can Tho (Vietnam), and with DrNguyen Nguyen was invited to conducta workshop in epidemiological methodsin Hanoi. He also presented his work onthe individualisation of fracture risk atthe 13th National Health OutcomesConference in Canberra
_ Dr Jackie Center was promoted toAssociate Professor (Conjoint) at theUniversity of New South Wales. She haspioneered the Dubbo study's work onpremature mortality after osteoporoticfractures in men and women. This workgained two prestigious oral presentationsat the recent American Society for Boneand Mineral Research meeting in
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OSTEOPOROSIS AND BONE BIOLOGY PROGRAM 41
Research Groups
Population, Individual and Genetic Determinants of Osteoporotic Fracture Risk and their OutcomesGroup Leaders Professor Tuan Nguyen and Associate Professor Jackie Center
The Dubbo Osteoporosis Epidemiology Study (DOES) began in 1989 and is the world'slongest running large-scale epidemiological study of osteoporotic fractures in men andwomen. We are using the DOES data to develop predictive models, based on multiplerisk factors, to identify men and women at high risk of fracture and to determine whowould benefit most from preventative interventions. We are also continuing to searchfor new osteoporosis genes that may predict those who are at low risk of osteoporosisand fractures - taking into account environmental factors such as physical activity, falls-related, nutrition, medication and hormonal factors. Finding and understanding howclinical factors and genetic factors affect bone biology and how they interact with eachother will help identify individuals for optimal use of existing therapies as well as identifytargets for novel therapies.
Bone Regulation Group Leader Dr Paul Baldock
The hallmark of osteoporosis is a reduction in bone density and therefore strength. It iscaused by an imbalance between bone formation and bone loss. Our group is, primarily,investigating the role of brain hormones, which influence bone formation and strength.Much of this work makes use of transgenic mouse models and is carried out incollaboration with researchers in the Neuroscience Program. The effect of this pathwayon bone is larger than any previously reported and this suggests a major approach tonew treatment.
Fracture Prevention - Clinical StudiesGroup Leader Professor John Eisman AO
Our clinical studies group continues to participate in multicentre international clinicaltrials evaluating potential osteoporosis treatments that are in the final stages ofpharmaceutical development. Involvement in these studies helps ensure we remain atthe cutting edge of knowledge of novel therapies and provides an entry pathway topharmaceutical interest in our novel developments.
Associate ProfessorJacqueline Center, headof the Bone Clinical andEpidemiology ResearchGroup, advises a patienton treatment for lowbone density.
Mouse olfactoryneuroepithelial sectionsprepared for adult stemcell analysis.
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NEUROSCIENCE PROGRAM 43
NEUROSCIENCE PROGRAMLeader Professor Herbert Herzog
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Program Highlights
_ Discovered that a brain chemicalNeuropeptide Y and its receptor arecritical for the proliferation of olfactorystem cells, so by blocking Y1 receptorstherapeutically, it may be possible tostimulate stem cells to differentiate intonew tissue when required
_ Demonstrated that mice geneticallyengineered to produce high levels ofPYY, a hormone that subdues appetiteafter a meal, were protected againstdiet-induced and genetic obesity
_ Discovered that people with low levelsof PYY have a higher risk of developingType 2 diabetes
_ Demonstrated a critical interplaybetween Neuropeptide Y and sexsteroids (oestrogen and testosterone),which both in turn regulate bonestrength and body fat
_ Showed that adult mouse tongue stemcells, an abundant and accessible sourceof stem cells, transplanted into the innerear of mice, improved noise-inducedhearing loss
_ Identified that different soundprocessing neurons in the brain showdifferent levels of excitation andinhibition, which affects how we hearsounds in a noisy room
_ Demonstrated that a hormone calledactivin-A stimulates stem cellproliferation and repair to the neuraldamage in Parkinson's disease,Alzheimer's and spinal cord injury, whichhas important therapeutic implications
Program Overview
The Neuroscience Research Program aims to increase our understandingof the neuronal systems involved in Eating Disorders, neurodegenerativedisorders such as Parkinson's disease and Alzheimer's disease as well ashearing loss. We aim to identify new therapeutic approaches for thesediseases with a special interest in regeneration of the nervous system fortherapeutic purposes with a specific emphasis on adult stem cells. A keyfocus is also the better understanding of the brain's control of energyhomeostasis (balancing energy intake and expenditure), which affectsfertility, mood, and weight gain.
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People Highlights
_ Professor Herbert Herzog was an invitedspeaker at the 9th International NPYCongress in Okinawa, Japan. He was alsoa presenter at the Keystone Symposia on Obesity, Fairmont Banff Springs,Alberta, Canada
_ Dr Amanda Sainsbury-Salis waspromoted to Associate Professor. Shewas an invited Conference Chair andspeaker at the International Associationfor the Study of Obesity (IASO) StockConference 2008 on Gender Aspects of Obesity, Bangkok, Thailand. She wasalso invited to present at the AustralianHealth and Medical Research Congress in Brisbane
_ Dr Sharon Oleskevich was an invitedspeaker at the international Adult StemCell-Biology and Clinical ApplicationsConference, Griffith University, Brisbane,and at the International College ofGeriatric Psychoneuropharmacology atthe University of NSW, Sydney
_ Andrea Abdipranoto and James Danielreceived their PhDs and Sandy Staytecompleted her honors year
_ Dr Bryce Vissel was a keynote speaker at the National Parkinson's Conferenceand is a founding member of theAustralian and New Zealand Spinal CordInjury Network
Dr Kharen Doyle, post-doctoral researcher, uses a'microtome' to slice wax-embedded tissue samples.Kharen investigates thepotential of adult neural stemcells for treatment ofneurodegenerative diseases.
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NEUROSCIENCE PROGRAM 45
Research Groups
Adult Stem Cell ResearchGroup Leader Professor John Shine AO FAA
Neural stem cells can be isolated from the adult olfactory neuroepithelium (situated inthe nose) and grown in the laboratory in the form of olfactory neurospheres. Thesestructures are three-dimensional aggregates of cells that are able to grow into neuronaland non-neuronal cells. The identity of the cell type within the olfactoryneuroepithelium that gives rise to these neural stem cells remains elusive. Our groupstudies the basic biology of adult olfactory stem cells with the aim of identifying,isolating and propagating these cells and in determining the conditions needed totransform them into the different types of nerve cells found in the brain, for example,those lost in Parkinson's or Alzheimer's disease.
Eating Disorders Research Group Leaders Professor Herbert Herzog and Associate Professor Amanda Sainsbury-Salis
Imbalances in the normal regulation of food intake can lead to obesity or severe weightloss. One of our laboratory's major goals is to understand how appetite and body weightare regulated. Defects in brain pathways that regulate these processes may be responsiblefor causing wasting conditions such as anorexia nervosa and cancer cachexia as well asthe metabolic resistance to weight loss occurring in overweight or obese people.
Our main focus is on the role of the appetite stimulating molecule neuropeptide Y (NPY)and the satiety inducing hormone PYY and how these molecules coordinate theregulation of appetite and body weight. Our research findings have implications for thetreatment of obesity, infertility, dwarfism, and osteoporosis, as well as anorexia nervosaand cancer cachexia.
Hearing Research Group Leader Dr Sharon Oleskevich
Our research strives to understand the mechanisms of hearing from the inner ear to thebrain. In the inner ear, degeneration of the hearing receptors (hair cells) leads to manyforms of deafness. We are exploring whether stem cell transplantation can provide apotential therapy for the treatment of hearing loss. Adult stem cells from sensoryorgans (taste, balance, smell) are being transplanted into mouse models of congenitaldeafness, age-related deafness, and noise-induced deafness. Specialised techniques instem cell biology, transplantation surgery, and hearing testing are combined todetermine if transplantation results in functional recovery of hearing. Taste stem cellshave shown a moderate effect on hearing levels following transplantation. Collaborationwith the National Centre for Adult Stem Cell Research and St Vincent's Hospital extendsour animal research to human tissue. An international collaboration is underway todetermine the anatomy and physiology of this synaptic plasticity usingelectrophysiology and electron microscopy.
Neurodegenerative Disorders - Repair & Regeneration Group Leader Dr Bryce Vissel
We are working on approaches to better understand and treat Parkinson's disease,Alzheimer's disease and spinal disorders, all of which are devastating neurodegenerativediseases. Our goal is to understand how to harness the brain's natural stem cells and/ormodulate nerve cells' connections. We investigate approaches to block nerve cell lossand we work to utilize the nervous system's own repair systems, to stimulate theformation of new nerve cells and their connections. We have identified newmechanisms to stimulate brain repair and we discovered potential approaches to blockneurodegeneration. Our research outcomes have significant implications for impactingthe well-being of people with brain and spinal cord disorders.
Post-doctoral researcher, Dr Nae Shiozawa-West,examines tissue samples.
Pipetting spleen cells.
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AUTOIMMUNITY RESEARCH UNIT 47
AUTOIMMUNITY RESEARCH UNITLeader Professor Fabienne Mackay
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Program Highlights
_ Discovered a new form of lupus in mice,which may correspond to a treatment-resistant form of lupus in humans andsuggests alternative kinds of treatmentfor some people
_ Identified a mechanism in the immunesystem (regulating the death of Blymphocytes activated by microbes)which is impaired in some autoimmuneconditions, leading to the survival ofactivated harmful cells
_ Sequenced the CXCR7 gene of childrenborn with congenital heart defects andidentified a mutation which impairs thegene's function, suggesting it is the likelycause of defects
_ Identified genetic regions containingdiabetes susceptibility genes associatedwith the pathogenic action of B cells
_ Analysed new genes that determine thelevels of NKT cells in mice, an importantimmune cell population that is able toprevent certain autoimmune diseasesand cancers
_ Performed whole genome expressionarrays on B cells from diabetic mice andnon-diabetic mice to aid identification ofnew genes that may contribute to thepathogenic activity of B cells causingType 1 diabetes
Program Summary
Autoimmune diseases affect approximately one in twenty people. Forsome unknown reason, they affect almost three times as many womenas men. Almost all autoimmune diseases appear without warning and can have serious consequences on morbidity and quality of life. They are the result of our immune system mounting a response against ourown body. More than forty human diseases are defined as havingautoimmunity as their definitive or probable cause and many treatmentscan be ineffective. Examples include Type 1 diabetes, systemic lupuserythematosus (SLE), Sjögren's syndrome, and Hashimoto's disease - all of which our unit investigates.
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People Highlights
_ Professor Fabienne Mackay was aninvited plenary speaker at the ResearchCenter for Allergy and Immunology - theJapanese Society for Immunology(RCAI-JSI) International Symposium onImmunology, in Yokohama, Japan. Shewas also an invited plenary speaker atthe Keystone conference en chemokinein Aussois, France; the Tri-conference onCytokines in San Francisco; and theannual American Immunology meeting inSan Diego. She gave the Ian Mackayoration at the 12th Australian workshopon Autoimmunity, and was a Chair andinvited symposium speaker at theAustralasian Immunology (ASI)conference in Canberra
_ Dr Martijn Bijker was awarded a Rubicon post-doctoral fellowship fromThe Netherlands
_ Sandra Gardam was awarded the Garvanthesis prize
_ Tyani Chan won the NSW Flowcytometry prize for her work on early Blymphocyte responses
_ Jessica Stolp from Dr Silveira's groupwas awarded the travel award to attendthe Australasian Society ImmunologyConference in Canberra. Dr Silveira co-organised the NSW branch AustralasianSociety Immunology Conference
Post-doctoral researcher DrMartijn Bijker undertakes flowcytometry analysis of spleencells to determine the size ofT cell populations. Dr Bijkerresearches the role of T cellsin autoimmune diseases. He isparticularly interested in howstress molecules affect theimmune system and thepotency of T cells.
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AUTOIMMUNITY RESEARCH UNIT 49
Research Groups
Autoimmune Disease MechanismsGroup Leader Professor Fabienne Mackay
One of our main areas of study concerns the unappreciated role of B lymphocytes inautoimmune diseases - uncovered from our work on the B cell activating factor (BAFF)- and how immune responses are affected by stress. When there is too much BAFF,harmful B cells live longer than they should and can damage healthy tissue. We want toknow how the oversupply of BAFF corrupts immune defences to drive autoimmunedisorders and why in other conditions it appears to be protective.
Our collaborative research on the link between stress, neuropeptide Y (NPY), and theimmune system continues to work towards building a better understanding of thecircumstances of NPY release and its effect on immune cells.
Unexpected data with some new B cell molecules had ramifications with heart researchand also cancer, which are now new areas of focus in the group via collaborations.
B Cell ImmunobiologyGroup Leaders Dr Robert Brink and Emeritus Professor Antony Basten AO FAA
Autoimmune diseases such as lupus, myasthenia gravis and hemolytic anemia can arisewhen B cells produce rogue antibodies that attack the body. We aim to identify thespecific genes and signaling pathways that regulate B cell survival, proliferation, anddifferentiation; as well as the molecules and cells that drive antibody production againstforeign structures and prevent antibody responses against ourselves. By understandinghow B cells function we hope to reveal new strategies for improving vaccines,controlling autoimmune disease, and treating B cell malignancies.
B Cell Tolerance & AutoimmunityGroup Leader Dr Pablo Silviera
Our ultimate goal is to prevent the immune system attacking the insulin producing betacells of the pancreas, which leads to Type 1 diabetes. Our research aims to identify thefaulty mechanisms that allow the B cells that recognise beta cell proteins to persist andthus activate the destructive T cells. We also aim to identify novel genes that controlthe generation and function of this aberrant population of B cells, findings that couldform the basis for new therapies to prevent or reverse Type 1 diabetes in humans.
PET (Positron EmissionTomography) scanshowing brown fat
distribution in a person.
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PITUITARY RESEARCH UNIT 51
PITUITARY RESEARCH UNITLeader Professor Ken Ho
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Program Highlights
_ Showed that growth hormone canreverse the breakdown of proteininduced by glucocorticoids and that this therapeutic potential is enhanced by co-treatment with an androgen
_ Completed the first demonstration of a placebo effect in sport in an evaluation on recreational athletes who wrongly thought they had beengiven growth hormone
_ Collected the first evidence that growth hormone enhances a selectiveaspect of physical performance, that of sprint capacity
_ In collaboration with the Bone Program,developed a mathematical (Bayesian)model for a growth hormone doping test (although it could be applied to anydiagnostic test) that incorporatesbiological and measurement variability of diagnostic markers
_ Continued to explore the feasibility of atest for growth hormone doping basedon the detection of gene expression inperipheral blood cells
_ Showed that ß-blockers, medicationused for treating blood pressure, may beadding to the burden of obesity throughits effects on energy metabolism
_ Demonstrated that the liver does notplay a role in the burning of body fatinduced by testosterone, a surprisingfinding given that it does play a roleburning fat induced by the femalehormone oestrogen
Program Overview
The pituitary gland produces key hormones that control body growth,strength, appetite, metabolism, mood and reproduction. An over or underactive pituitary gland can lead to a range of diseases from dwarfism inchildren to infertility, mood disorders, muscle wasting, obesity anddiabetes in adults. The Unit's major focus is understanding the role of thepituitary gland in controlling body metabolism, composition and physicalfunction. Its effects underlie the many key health problems such asobesity, osteoporosis and sarcopaenia (muscle wasting).
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Dr Paul Lee, endocrinologistand PhD student, reviews a
PET (Positron EmissionTomogoraphy) scan. Dr Lee
analyses RNA in brown fat tounderstand how it develops.
One day, brown fat may be atarget for treating obesity.
_ Professor Ken Ho was awarded the Asia-Oceania Medal by the British EndocrineSociety, invited as Keynote Speaker bythe Irish Endocrine Society, invited toserve on the Annual Meetings SteeringCommittee of the US Endocrine Societyand joined the Editorial Board ofEndocrinology
_ Dr Paul Lee was awarded a PostgraduateMedical Scholarship by the NHMRC forstudies towards a PhD on the metaboliceffects of ß-blockers. He was therecipient of the Wiley Blackwell ClinicalExcellence Award from the RoyalAustralasian College of Physicians; theYoung Investigators Award by theInternal Medicine Society of Australiaand New Zealand; and received TravelGrants from Royal Australasian Collegeof Physicians, The Endocrine Society ofAustralia and the Growth HormoneResearch Society
_ Dr Vita Birzniece received a Poster Prizefrom the US Endocrine Society, theAustralasian Branch of Women inEndocrinology Award from TheEndocrine Society of Australia and atravel award from the Growth HormoneResearch Society
_ Dr Udo Meinhardt, a Postdoctoral Fellow,was awarded a prize for the best ClinicalResearch at the International GrowthHormone and IGF Congress in Genoa
_ Ms Jennifer Hansen's work was selectedby the US Endocrine Society for SpecialMedia Interest. The work was reportedby a range of agencies including theTimes, CBS News, Fox News, TheAustralian, Discovery and Forbes magazine
_ Dr Akira Sata was awarded an AustralianGovernment Endeavour Fellowship toundertake Postdoctoral studies on sexsteroid modulation of Growth Hormonesignalling
_ Dr Jing Ting Zhao filled the position ofScientific Head, bringing strongmolecular skills to the Unit
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PITUITARY RESEARCH UNIT 53
Research Groups
Hormones, Metabolism and Health
Work from the Unit has shown that Growth Hormone (GH) plays a major role as ametabolic hormone throughout adult life. The ongoing work investigates how the GHsystem is controlled, what health problems arise from its disturbance and what diseasestates can benefit from the use of GH. We have discovered that sex hormones exert amajor effect on the GH system and we postulate that these are likely to influence howGH controls the metabolic process. We have shown that the female hormone oestrogenblocks, while male hormone testosterone boosts, the action of GH. Under activeinvestigation are the metabolic consequences of compounds called SERMs, which aresynthetic oestrogen-like compounds, widely used for the treatment of osteoporosis andbreast cancer. The work also explores the potential benefit of combining GH with malehormones to treat muscle wasting.
Complementary work in the laboratory addresses the cellular and molecular mechanismsby which sex steroids modify the action of GH action and identifying novel GHregulated genes. A parallel project extends our understanding of how female hormonesinteract with prolactin, a pituitary hormone that is structurally related to GH, in theregulation of lactation and mammary development in collaboration with theDevelopment Group of the Cancer Program.
Growth Hormone (GH) Doping
We are aiming to develop new approaches for the detection of GH doping and studyingits effects on performance.
We have evaluated the merits of GH responsive blood proteins and the different formsof GH, called isoforms, for detection of GH abuse. We have found that the mostpromising of these markers can detect GH for several weeks after GH is taken and thatone marker is even more sensitive when testosterone is also used. This should enablemore cheats to be detected using these tests. In collaboration with the CSIRO, we areutilising microarray gene profiling and gene pathway analysis aiming to develop a genefingerprint test based on gene expression profiling of white blood cells. We have foundfor the first time that GH enhances performance but this benefit is confined only tosprint capacity and not strength, power or endurance.
The Unit has also received major funding worth over one million dollars over 3 yearsfrom the World Anti-Doping Agency for the gene expression study.
Sympathetic Nervous System, Drugs and Obesity
We are addressing the metabolic significance of therapeutic blockade of thesympathetic nervous system, which plays a major role in providing energy for vitalfunctions. Stimulation of the sympathetic nervous system increases a host ofcardiovascular and metabolic responses that lead to increased cardiac output and fuelutilisation. These actions are mediated by the beta-adrenergic stimulation. Our projecttests the hypothesis that beta-blockers increase adiposity by reducing metabolic rate,fat oxidation and exercise capacity. Because of their widespread use, their actions onenergy metabolism may worsen the burden of obesity in the community. Conversely,judicious use of agents that activate the system may cause weight loss.
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CORE RESEARCH FACILITIES 55
CORE RESEARCH FACILITIES
Technology is an important component of being competitive in medicalscience. Garvan's core research facilities contain state-of-the-art equipmentthat enables our scientists to perform the necessary experiments tobetter understand disease processes. A highly trained manager overseesthe facilities which are also available to external researchers.
Australian Cancer Research Foundation (ACRF) Facility for the Molecular Geneticsof Cancer houses equipment that can detect and analyse genetic sequence variationssuch as gene losses, mutations, expression, and methylation on a large scale. A diversityof platforms is available within the facility to facilitate research within and outside theGarvan Institute. The goals of the facility are aimed at high-throughput, sensitivity,accuracy and cost effectiveness. In addition to sequencing and methylation analysisservices, there is now a mouse genotyping service available for all researchers in NSW.
Gene Chip Facility contains the Affymetrix Microarray System that is used to comparethe levels of gene transcripts in tissue samples. It is used to find potential genes ofinterest, the subsets of which can then be further analysed in the ACRF Unit that canhandle large numbers of samples. Garvan was the first in Australia to establish the system.
Australian BioResources (ABR) holds mouse production colonies under clean roomconditions for Garvan and other medical research organisations in NSW. The BiologicalTesting Facility receives mice from ABR for holding in specialised experimental zones toenable quality animal-based research.
Clinical Research Facility runs Garvan clinical research projects such as those that lookat the effect of hormones (e.g. growth hormone, sex steroid hormones, insulin) ondifferent metabolic systems. Staff also monitor volunteers involved in pharmaceuticalclinical trials, such as those for osteoporosis medications.
Peter Wills Bioinformatics Centre applies techniques derived from disciplines such asapplied mathematics, statistics and computer science to understand, organise andanalyse biological data. This includes the housing of both clinical and microarray data,and the building of computer programs for querying and analysing these datasets.Examples of these programs include Cansto for managing clinical cancer data, Stuart for animal records management and Garvan's GeneSpring WorkGroup - a microarrayarchiving and analysis environment. CanSto is used across Australia by the AustralianProstate Cancer Collaboration for all their clinical information management. Garvan'sGeneSpring WorkGroup server houses microarray experiment results for researchersacross Australia.
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Flow Cytometry Facility encompasses instruments used for cell analysis and provides acell sorting service to allow the separation of up to four populations of cell types fromany body fluid or tissue suspension. Through the use of laser, optical and fluidicstechnology the pure population of cells can be separated on the basis of multiplephenotypic and functional characteristics, and then grown as pure cultures, used toextract RNA or DNA for genetic analyses, or implanted into animal models, for functionalassays and therapeutics.
Pieter Huveneers Molecular Imaging Facility consists of a number of state-of-the-artmicroscopes which, using a variety of fluorescence based techniques, are capable ofimaging tissue, cells, intracellular organelles and even multiple individual molecules in livecells. Using techniques such as Total Internal Reflection Fluorescence (TIRF) microscopywe are able to image events occurring on or near the surface of a cell. Using laserscanning confocal microscopy we can precisely image 'slices' of samples which can bereconstructed into a 3D representation for analysis. These provide our scientists withthe best possible means of identifying where and when molecules of interest are innormal tissue and how this may differ in disease.
Manager of the FlowCytometry Facility, MrChristopher Brownlee, checksthe laser alignments onFACSVantage (a cell sortingflow cytometer).
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MANAGEMENT HIGHLIGHTS
_ As an integral part of the developmentof the St Vincent's Research Precinct,Garvan participated in the completionand occupancy of the Lowy PackerBuilding, housing the Victor ChangCardiac Research Institute and several of St Vincent's research groups
_ Developed a Precinct ManagementAgreement outlining the operation ofvarious essential services, which will beshared between the Garvan and LowyPacker Buildings, such as the loadingdock, stores and emergency generators
_ Relocated and significantly enhancedGlass Wash and Media Prep facilities asintegral facilities for the Precinct
_ Focused on energy saving initiatives toreduce our carbon footprint, including:upgrade of lighting to energy efficientfluorescent tubes; installation ofmovement detectors to activate lightingin irregular use spaces; and adjustmentto the central air conditioning systems
_ Redeveloped space (vacated by GlassWash and Media Prep) for variousgroups within Operations, including anexpanded Engineering space, improvedInstrument Repair Workshops andexpanded desk space for other groups
_ Received two 90,000 vial capacityvapour phase cryogenic vessels inresponse to the demand fromresearchers for more secure and stablestorage for biological samples. Thisleading edge technology is supported bya software application (for tracking andmanaging samples), designed anddeveloped by Garvan IT
_ Developed and implemented an on-lineOccupational Health and Safetyinduction system to ensure that Garvanremains a safe working environment,including: installation of two automatedexternal defibrillator (AED) units tofurther enhance a safe workingenvironment; development of a sitespecific emergency flip chart, which hasbeen installed at key points; andcompletion of risk assessments for allchemicals on the Institute's knownchemical inventory
_ Opened our new animal facility,Australian BioResources, near Moss Vale,involving the staged relocation of 14Garvan staff, 12,000 mice andmiscellaneous equipment, as well as theco-ordinated receipt of another 1,500mice from seven partner institutes. Thebuilding utilises state-of-the-artoperating and caging systems.
_ Received two prestigious awards fromthe NSW Master Builders Association(MBA) for the Moss Vale facility. One for the best health building, $10 - 25million. The other as the NSW MBA'sEnergy Efficiency Building Award,reflecting Garvan's express desire tohave a low impact, environmentallyfriendly facility.
_ Upgraded operating and data /communication systems prior to openingthe new animal facility, to supportefficient large-scale operations and toprovide improved data access
_ Upgraded the PABX telephone system at Garvan to include voice-over-IP(VOIP) services to the animal breedingfacility in Moss Vale, building in capacityfor future growth
_ Helped support a growing, geographicallydispersed research community byreleasing new and upgraded versions ofthe Publications, Grants and Cryogenicsstorage systems. Additionally, Garvan'sown cancer research solution, CanSto,was installed at Royal North ShoreHospital, Concord Hospital and CharlesGardner Hospital in Perth
_ Expanded the technologies available toGarvan researchers by establishing appliedcollaborations with CSIRO in the area ofmolecular imaging and structural biology
_ Completed several agreements withinternational biotech and diagnosticcompanies to develop therapeuticresponse tests for neurodegenerativedisease and to discover novel cancerbiomarkers
_ Submitted two funding proposals to the$30m pre-seed Medical ResearchCommercialisation Fund to advance apromising therapeutic and a diagnosticproject in the area of Type 2 diabetes
_ Continued training of Garvan researchersin intellectual property matters includingpatent searching and what is necessaryto develop early stage findings intoclinically attractive projects
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BUSINESS DEVELOPMENT 59
BUSINESS DEVELOPMENT
Overview
The Business Development team, under the leadership of Christina Hardy, engages withthe pharmaceutical and biotech sector and partners with other academic organisationsto take Garvan's research discoveries one step closer towards the development of newtreatments and diagnostic tests. Working closely with Garvan scientists, the BusinessDevelopment team is responsible for all aspects of commercialisation from monitoringresearch activities to maximising early capture of intellectual property, identifyingpharma/biotech market opportunities, and negotiating and managing commercialagreements. Importantly the Business Development team establishes appliedcollaborations with organisations who have additional technologies which greatlyincrease the potential for Garvan's breakthroughs to be developed for clinical use.
The Garvan patent portfolio comprises 39 patent families covering treatment,diagnostics and screening categories.
G2 Therapies and Novo Nordisk G2 Therapies is a private company, chaired by Dr John Schubert, which develops andcommercialises antibody-based therapeutics for inflammation. Founded at Garvan in2002, major investors include AMWIN and Baron Nominees.
In early 2006, G2 announced the signing of a major research, development andlicensing agreement with Danish healthcare company Novo Nordisk. The terms of theagreement include an upfront payment, success-based milestone payments, androyalties on commercialised therapeutics.
Novo Nordisk and G2 Therapies have recently advanced the lead anti-C5aR monoclonalantibody to human clinical trials in late 2008. Anti-C5aR antibody treatment holdspromise for a number of inflammatory conditions including lupus, rheumatoid arthritisand other autoimmune diseases.
Business Development Advisory Council
The Business Development AdvisoryCouncil (BDAC) includes severalrepresentatives from the biotech andpharmaceutical industries.
Dr Lisa McIntyre (Chair) Director, L.E.K. Consulting
Bill Ferris AC, Board Chairman, Garvan
Professor John Shine AO FAA, Executive Director, Garvan
Dr George MooreExternal Director
Dr Merilyn Sleigh, External Director
Peter Carre, CEO, Burrill Australia
Christina Hardy, Director, Business Development & Legal Affairs, Garvan
John Dakin, Chief Operating Officer, Garvan
Dr Robert BrinkGroup Leader, Immunology Program,Garvan
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60 GARVAN COMMUNITY
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GARVAN COMMUNITY
Life Governors
Allind Pty LimitedAmadeus Energy LimitedMr John ArmatiAustralian Cancer Research FoundationASX-Reuters Charity FoundationAustralian Deafness Research FoundationAustralian Securities ExchangeThe Blundy FamilyCoca-Cola AmatilMr Charles P Curran AC
The Curran FoundationLady (Mary) Fairfax AC OBE
Ferris Family FoundationMr Laurence S Freedman AM
Miss Felicia D GarvanMr James Patrick Garvan & FamilyGeorge Patterson Pty LimitedMr and Mrs B & A GingesMr Paul & Mrs Judy HennessyHIH Insurance LtdMr Pieter H HuveneersMrs Virginia KahlbetzerMr T Kennedy AM & Mrs C KennedyMr Ralph and Mrs Lorraine KeyesThe Kinghorn FoundationMrs Mabs MelvilleMLC Community FoundationNational Australia Bank LtdDr Graham O'NeillOrder of the Eastern Star Chapter No. 38Mr K Packer AC
The Paramor FamilyThe Ritchie FamilyMr Tim and Mrs Sally SimsMr Robert Strauss MBE
Mr Laurie SuttonThe Lady Proud FoundationThe Petre FoundationWestfield Holdings LtdE J Whitten FoundationMr Ray Williams
Partners for the Future
Mrs M AbercrombieMrs Margaret AdamsDr W Michael BakerMs James BelgerMr Peter BinnieKen BloxsomMs Linda BoothMr Earle & Mrs Marlene BoutwellMr Alan & Mrs Anne BoyleKen & Betty BrownMrs Judith ClarkMrs Madeline CoelhoMr Jock CrooksMr Rodney F DarkeMs Cristine DavisonMrs Marlene DixonMr John DobiesMrs Phillipa DorinMs Daile FalconerMr Gabriel & Mrs Joan FaragoMs Jan FosterMr Michael & Mrs Joy FoulshamElizabeth FyffeMrs Carmel GillettMiss Flo GreeneDr A.N. GyoryMrs Jean B HaleDr Bronia HatfieldMs Heather Patricia HindleMr J K L HootonMiss V JenkinsByram & Deborah JohnstonMrs Florence JonesMrs Virginia KahlbetzerMs Lili KochRoberta Lauchlan and Barry ThompsonMr Keith LineMrs Adell LittlejohnMs Maria LydakiDenise MaddocksWJ and PA McNamaraMrs Mabs Melville
Mr John & Mrs Mary MillerMiss Helen MorganMr Peter OliveMrs Lesley PowellMr George QuiggMrs Judy RadeckiTanya RoddanIn memory of Sonia Gabrielle Saba-LoseyMiss Vi SaintMs Coral SaundersMiss Thelma ShepherdMrs Cynthia SouthwellMiss H StockmanMr Leonard TowersMrs Judith Wheeldon AM
Mrs Jean WhittakerDr Eva WickiMs Faye Margaret WilliamsMary and Herbert MorrisMs Jacquie ColeDr Norman Marshall
Volunteers
Janet BarkellKaye BlaiklockDeirdre BlakemoreGraham CurtisMargarita FieldLyndie HemeryMrs Edna HuttonLynne JonesJuliet KirkpatrickJanice LeeJohn McInerneyMargaret McInnesBob NeilsonJoan NeilsonJean PushongJulie ReidPhilip TwiggBill Upton
A thank you also to the volunteers fromASIC, MLC, NAB, and BNP Paribas whoassisted us with the 2008 Open Day.
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GARVAN COMMUNITY 61
Garvan Supporters
A W Edwards Pty LimitedMr Chris M AbbottAccentureAGL Energy LimitedMichael AhrensMr Len AinsworthAke Ake FundAlcoa Australia Rolled ProductsAlcoa FoundationAllen & Unwin Pty LtdAmadeus Energy LimitedAmerican ExpressAMP FoundationMr Neil AndersonAnti-doping Research Program of the
Australian Government Department ofCommunications, InformationTechnology and the Arts (DCITA)
ARC/NHMRC Network - FABLS Support Scheme
Ascham SchoolAustralian Cancer Research FoundationAustralian Deafness Research FoundationThe Australian Ladies Variety Association IncAustralian Research CouncilAustralian Rotary Health Research FundAustralian Securities & Investments
CommissionAustralian Securities ExchangeAvalon QuiltersBain & CompanyMr Klaus BartoschProfessor Antony BastenMr Douglas BattersbyMrs Marie BennettMiss Tania BettsBHP Billiton Community ProgramMrs Kaye BlaiklockBNP ParibasBNP Paribas FoundationMr Roy L BockholtMrs Gay Boersma
Mrs Thelma Susan BonnerMrs D BonserMs Margaret BowersMs Louisa BoyleMr and Mrs G & C BradleyDr Ruth Bright & Dr Desmond BrightKen & Betty BrownMrs Kate BuchananMr G BushbyIn Memory of Yvonne BuwaldaCAF AustraliaCancer Council NSWCancer Institute NSWMrs Helen CallanderCarol and Steve Rogers Memorial
Charity DayCastle Harlan IncMr Andrew ChapmanMr Chris Chapman & Dr Cath ChapmanMr Craig ChapmanMs Janet ChesterClive and Vera Ramaciotti FoundationMs Melinda ConradThe Corio FoundationMr Stanley CostiganBrett & Susan CourtenayMr Richard CropleyCSR LimitedCure Cancer Australia Foundation Mr & Mrs R CusickDairy Farmers Co-operative Limited
Employees' Provident FundMr Rodney F DarkeMr Peter DavidProfessor J G & Dr J R DavisMr Robert DavisMr & Mrs Tony & Coleen De SaxeDepartment of Foreign Affairs and TradeDepartment of Innovation, Industry,
Science and Research Diabetes Australia Research Trust Geoff and Dawn DixonMs Rochelle DizonDominion Private Clients
Mrs J DoyleMr Phil DurneyMr Andrew EgerEli Lilly Australia Mr Patrick J ElliottErnest Heine Family Foundation and
Mrs Janice GibsonMr Andrew EvansMrs Margaret EvansLady (Mary) Fairfax AC OBE
Mr Jonathon A FellerMr Tom G FentonFerris Family FoundationMs Jane ForsterMr Michael & Mrs Joy FoulshamFoundation for Prader-Willi ResearchElizabeth FyffeGadens Lawyers Sydney Pty LtdEric & Tonia GaleMr Justin H GardenerDr William GarrettGlaxoSmithKline AustraliaJohn GlennieCherie Glick and family for JoeMr Cyril GoldingMrs Elizabeth Goldsmithgraysonline.comThe Greatorex FoundationSharon GreenGresham Partners LimitedMr J GriceMrs Enid GriffinMrs R A GrossWilliam A and Laura H GruyMr & Mrs G F & B C GschwenterDr Jenny GuntonGynaecological Oncology (GO)
Research FundAlan HellicarH Kallinikos Pty LimitedMrs Jean B HaleThe Jessica & Wallace Hore FoundationMrs Ann HansonMr Loftus Harris AM
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Ms Betty HaughMr & Mrs Bill & Alison HaywardMr Alan HeggieMeredith HellicarMr Paul & Mrs Judy HennessyDr G J HiattMr I HolmesDr & Mrs Francis & Marie HooperMr J K L HootonMs Jessica HoreMrs Sue HowiesonMrs L A HudsonStanley Hunt OAM
Mr Robin & Mrs Beatrice HutcheonMr Pieter H HuveneersMr & Mrs M IsaacsMr Phill IsaacsThe Hon Justice Peter M. JacobsonMr R JarvisJohn & Connie Kennedy Charitable TrustJohn Lamble FoundationJohn T Reid Charitable TrustsMrs Sheila M JohnstoneMr Alan JoyceThe Juvenile Diabetes Research
Foundation (JDRF)Mrs Virginia KahlbetzerLady Catherine Kater AM
Mr & Mrs Patrick & Beryl KeaneMrs Helen KeirProfessor Geoffrey Kellerman AO
The Ken & Alse Chilton Charitable TrustMr T Kennedy AM & Mrs C KennedyMr Raymond KentMr Ralph and Mrs Lorraine KeyesThe Kinghorn FoundationMrs A KirbyMr W Bruce Kirkpatrick & Mrs Juliet
KirkpatrickMr John T KneeshawMr Philip KnoxKPMGMs Josie La SpinaThe Lady Proud Foundation
Mr Robert LanderosIn Memory of Michael Ison LargeMs Nita LavigneMr Jeremy LaymanLions Club of Hawkesbury Bells Line Inc.Lord Mayor's Charitable Foundation
(Melbourne)Mr Michael LoweMr Bramwell LucasMs Maria LydakiMrs Ann MacintoshMacquarie Group FoundationMallesons Stephen JaquesMr A J & Mrs S A MaloufMr Roy ManassenThe Mandarin ClubMr R & Mrs S Maple-BrownDr Karen MardelMr Philip Mason & Ms Alexandra JoelThe Hon John & Mrs Dympna MatthewsMr Peter McGovernWJ and PA McNamaraMedical Benefits Fund (MBF)Medtronic Australasia Pty LtdMrs Mabs MelvilleMerck Sharp & Dohme (Aust) Pty LimitedThe Michael & Andrew Buxton FoundationMr Neill MillerMrs Wendy MillhouseMLC Community FoundationMr & Mrs R & A MoleGeoff & Jan MolesMr Warren MorleyMs Lesley MorrisonMotor Neurone Disease Research Institute
of Australia MSM Milling Pty LtdMr Peter MurphyMr S MurrayMr J MuyskenNational Breast Cancer FoundationNational Health and Medical Research
CouncilNational Institute of Complementary
Medicine
National Institutes of Health The N E Pendergast Charitable Trust FundMr James NilsonMr & Mrs Leigh & Binnie NormanNovartis Pharmaceuticals AustraliaThe NSW Cancer CouncilNSW Department of Health & AgeingNSW Office for Science and Medical
ResearchNuclear Medicine and Bone Densitometry,
SVHMr Michael O'Dea AM & Mrs Marianne
O'DeaMr J O'FarrellDr Graham O'NeillOrange & District Breast Cancer SupportOrder of the Eastern Star Chapter No. 67Mr Wayne O'ToolePacific Equity PartnersMiss Winnie PangThe Paramor FamilyPark Hyatt SydneyIan PaulPerpetual TrusteesPfizer Australia Pfizer Global Research and DevelopmentPfizer InternationalPrader-Willi Syndrome Association of
NSW (Aust) IncPremier Media GroupPricewaterhouse Coopers FoundationProstate Cancer Centre, St Vincent's
HospitalProstate Cancer Foundation of AustraliaPublic Trustee NSWQantas Airways LimitedQuota InternationalMrs E RamsdenMr Roy RandallRebecca L Cooper Medical Research
Foundation Mr Jean RedmanBrad & Lisa ReesRetire@Ease Financial Planning
Garvan Research FoundationCEO, Ms Carole Renouf, withMLC CEO, Mr Steve Tuckerand Manager of Garvan's FlowCytometry Facility, MrChristopher Brownlee. TheMLC Community Foundationhas pledged $1 million to thefacility over 5 years.
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Mr George RiskMrs Judy RoachThe Rodney & Judith O'Neil FoundationMrs Deanne RoozRosemary Pryor FoundationMs Kelly RosmainRotary Club of HurstvilleRoth Charitable FoundationMr Garry RothwellRoy Young ChemistRT Hall TrustMrs G RyanMr Martin SachsSanofi-aventisMr D & Mrs A SaulMr L SeamanMr Graham SeeJan ShaddockMr & Mrs T & J ShanahanMrs D ShannonMrs Lindsey ShawMr David ShmithMr Richard SimonsSkipper-Jacobs Charitable TrustJoseph Skrynski AO and Roslyn HorinMr M SlavichMr Graham SmithMr Barry SmorgonMrs Shirley SmythMr Frank SnoeysMr & Mrs George & Sabrina SnowMr Neil SpitzerSt Vincent's Clinic Foundation Miss Alison StephenStrategic IndustriesMs Joyce StrongProfessor Rob Sutherland FAA
Swiss National FundSydney Ultrasound for WomenMr Nick Tait OBE & Mrs Mimi TaitThomas Hare Investments LimitedMrs Margaret TurnerMrs A UdyUniversity of NSW
Mr Peter UnwinVictor Chang Cardiac Research InstituteVittoria CoffeeVoice & DataJohn & Megan WadeWade Civil Engineering Pty LtdMrs Caroline WalderDr JR WarnefordMs Alexandra WedutenkoWestpac Banking CorporationMrs Judith Wheeldon AM
Mr Alan WhitfieldE J Whitten FoundationIn Memory of the Late Kathrin Nell A
WilshireMr William WilsonWitcheryEmil WittonWood Family FoundationMr J & Mrs L WoolfMr Andrew WrightMs Pamela WrightDr Stan J WrightXLP Research Trust (UK)Mr Ralph W YoungMr Stanley Young
Bequests
Estate of the Late Gloria M BackhusEstate of the Late Brenda M BismireEstate of the Late Denzil de Ferrars
CarringtonEstate of the Late Milly DinjaskiEstate of The Late Charles Edward Lawn
and Marjorie Grace LawnEstate of the Late Leslie McAllisterEstate of the Late Henry R McQuirkEstate of the Late Phyllis Maude O'HanlonEstate of the Late Babette Josephine RyanEstate of the Late George W SteedEstate of the Late Charlotte M TrunshnigEstate of the Late Betty A Williams
Dr Nae Shiozawa-Westdiscusses her research withMrs Rosemary Pryor, who hasdonated $1 million to Garvan'sNeuroscience Program.
GOVERNANCE
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GOVERNANCE 65
Garvan Institute Board
Bill Ferris AC
ChairmanNominated by the Trustees of St Vincent'sHospital
Bill Ferris is Executive Chairman of theCHAMP Private Equity Group, one ofAustralia's leading private capital groups,providing venture capital, expansioncapital and management buyout funding in Australasia. Mr Ferris is Chair of theGarvan Institute of Medical Research andrecently appointed Chair of the Health and Hospitals Fund Advisory Board as part of the Federal Government's Nation-Building Funds initiative. Formerdirectorships include: Chairman, AustralianTrade Commission (Austrade), AustarUnited Communications Limited andBradken Resources Pty Ltd. Other currentdirectorships include: Director, GarvanResearch Foundation.
Mr Ferris was made an Officer in theOrder of Australia in 1990 for services tothe export industry and in 2008 wasmade Companion in the Order of Australiafor his philanthropic activities and his rolein the establishment of the private equitysector in Australia.
Martin Hoffman TreasurerNominated by the Sisters of Charity
Martin Hoffman is the principal of UlyssesVentures, a provider of advisory servicesand seed investment to early-stage digitalmedia and technology companies. He waspreviously CEO of Loop Mobile Limited, alisted provider of mobile chat andcommunity services internationally, and of NineMSN, Australia's largest internetmedia company. He has also held seniormanagement roles with Fairfax Media and Optus.
Graham J BradleyNominated by the Garvan ResearchFoundation
Graham Bradley is a professional companydirector. Mr Bradley is Chairman ofStockland Corporation Limited, HSBC BankAustralia Limited and Anglo AmericanAustralia Limited. From 1995 to 2003 hewas Managing Director of PerpetualAustralia. He is a former partner ofMcKinsey & Company, managementconsultants, and a former nationalmanaging partner of Blake Dawson. MrBradley was appointed Chairman ofGarvan Research Foundation in June 1999and joined the Garvan Institute Board inNovember 1999.
Nicholas CurtisNominated by the Trustees of St Vincent's Hospital
Nicholas Curtis has a background ininvestment banking and the resourcesindustry. He is Executive Chairman ofLynas Corporation Limited, an Australianpublic company specialising in rare earths.Mr Curtis was appointed as Chairman ofthe Board of St Vincents & Mater HealthSydney in August 2004 and also serves as a director of the Sisters of CharityHealth Service.
Mary FoleyNominated by the Sisters of Charity
Mary Foley held the position of the ChiefExecutive Officer, St Vincents & MaterHealth Sydney until early 2008. Ms Foleyis currently the National Health PracticeLeader at PricewaterhouseCoopers.Previous positions include Deputy Head,NSW Department of Health and ExecutiveDirector, NSW Office of Health Policy andsenior executive management positionsfor Mayne Nickless private health carebusiness. Ms Foley is Deputy Chancellor
and a member of the Board of Trustees,University of Western Sydney as well as amember of the Board of Governors ofUniversity of Notre Dame Australia. MsFoley was NSW Telstra Businesswoman ofthe Year in 1998 and was awarded theCentenary Medal in 2003 for service toAustralian society in business leadership.Ms Foley stepped down from the Boardsof the Garvan Institute and GarvanResearch Foundation in March 2008.
Lisa McIntyreNominated by the Federal Minister forHealth
Dr Lisa McIntyre is a partner with thestrategy consulting firm LEK Consultingand head of LEK’s Asia Pacific Life Sciencespractice. She has over 15 years consultingexperience for the biotechnology sectorand has worked with over 100 differentbiotechnology and life sciences clientsprimarily focusing on the challengesassociated with commercialising innovation.Dr McIntyre relocated to Sydney in 2002after nine years in the United States co-heading LEK’s Life Sciences practice whereshe advised many of the world’s leadingbiotechnology companies. She is also adirector of Biotech Capital Ltd and AtCorMedical Pty Ltd.
Greg ParamorNominated by the Garvan ResearchFoundation
Greg Paramor has been involved in the realestate and property funds managementindustry for approximately 35 years. Mr Paramor was appointed ManagingDirector of the Mirvac Group followingthe acquisition of the James FieldingGroup in January 2005. He is the pastPresident of the Property Council ofAustralia and the Investment FundsAssociation of Australia. He is currently a
Bill Ferris AC
Martin Hoffman
Graham J Bradley
Nicholas Curtis
Mary Foley
Lisa McIntyre
Greg Paramor
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director of a number of companies,including the National Breast CancerFoundation. He is a Fellow of the AustralianProperty Institute and a Fellow of TheRoyal Chartered Institute of Surveyors.
Sister Carol Pedersen RSC
Nominated by the Sisters of Charity
Sister Carol Pedersen graduated as atrained nurse at St Vincent's Sydney in1963 and is a Sister of Charity. She holdsa PhD from UNSW and a BSW (Hons 1)from the same institution. She also holdsan Advanced Diploma from the SydneyCollege of Homoeopathic Medicine, andhas completed postgraduate work,obtaining an Associate Diploma inAdvanced Homoeopathic Medicine. Forover 20 years Sr Carol was a member ofvarious Human Research EthicsCommittees, and was active at national,state and local levels in the developmentof Alcohol and Drug Services.
Warren ScottNominated by the NSW Minister for Health
Warren Scott is a director of Citigroup and is General Counsel and ManagingDirector in Australia. He is Chairman,Woolcock Institute of Medical Research, as well as a delegate to the AustralianAmerican Leadership Dialogue, the LawSociety of New South Wales, theAmerican Bar Association, the New YorkBar Association and the California BarAssociation. Warren is admitted as asolicitor in New South Wales and as alawyer in New York and California.
John Shine AO FAA
Appointed by the Garvan Institute Board
Professor John Shine is Executive Directorof the Garvan Institute of MedicalResearch and a board member of theGarvan Research Foundation. He isProfessor of Molecular Biology andProfessor of Medicine at the University of NSW, and a director of many scientific,research and medical bodies throughoutAustralia, including the recent ex-Chairman of the National Health andMedical Research Council (NHMRC) anduntil 2006 a member of the PrimeMinister's Science, Engineering &Innovation Council (PMSEIC).
Peter J SmithNominated by the University of NSW
Professor Smith is Dean, Faculty ofMedicine, the University of New SouthWales. He specialised in cancer medicineand research following study in Australia,USA and Germany. He has held seniorhospital management posts in Brisbaneand Melbourne, and senior academicappointments at the Universities ofQueensland, Melbourne and Auckland. He has served in a consulting role toGovernment, including as Chair of therecent Inquiry into Vietnam VeteransCancer Incidence and Mortality. ProfessorSmith is currently a Director of St Vincents& Mater Health Sydney, NewSouthInnovations, MedSys Assurance (NZ) and anumber of research centres and institutes.
Bernadette TobinNominated by the Trustees of St Vincent's Hospital
Associate Professor Bernadette Tobin isDirector of the Plunkett Centre for Ethicsat St Vincent's Hospital, Sydney, andReader in Philosophy at the AustralianCatholic University. Dr Tobin is HonoraryEthicist at the Children's Hospital atWestmead, Honorary Associate Professorin the Faculty of Medicine at the Universityof Sydney, and Conjoint AssociateProfessor in the School of Medicine at theUniversity of New South Wales. Sheserved for three triennia on the AustralianHealth Ethics Committee, a principalcommittee of the NHMRC. She alsochaired the drafting group which preparedthe first Code of Ethics for Catholic Healthand Aged Care Services in Australia.
Ronald TrentNominated by the Federal Minister for Health
Ronald Trent is Professor of MolecularGenetics, University of Sydney and Headof the Department of Molecular andClinical Genetics, Royal Prince AlfredHospital. He is the Chairman of theAdvisory Committee for the University'srecently formed Forensic Medicine &Science Network. He has been a memberof the NHMRC Research Committee since1997 and has been Chairman of theNHMRC Human Genetics AdvisoryCommittee as well as a member of theNHMRC Council since 2006.
Sister Carol Pedersen RSC
Warren Scott
John Shine AO FAA
Peter J Smith
Bernadette Tobin
Ronald Trent
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Graham J Bradley Chairman
Graham Bradley is a professional companydirector. Mr Bradley is Chairman ofStockland Corporation Limited, HSBC BankAustralia Limited and Anglo AmericanAustralia Limited. From 1995 to 2003 hewas Managing Director of PerpetualLimited. He is a former partner ofMcKinsey & Company, managementconsultants, and a former nationalmanaging partner of Blake Dawson. MrBradley was appointed Chairman ofGarvan Research Foundation in June 1999 and joined the Garvan InstituteBoard in November 1999.
Jane AllenJane is the Managing Partner of EgonZehnder International's Sydney office, and co-leader of their Australian Practice,where she focuses on CEO and Boardappointments in Australia. EZI is theworld's largest privately held search firmwith more than 380 consultants located in63 wholly owned offices in 38 countries.The firm specialises in senior levelexecutive search, board consulting anddirector search, management appraisals,and talent management. Jane has been atEgon Zehnder International for 10 years.In addition to her local role she also holdsa global strategy leadership role in one ofthe Firm's core client practices, after
leading the practice group in Asia Pacificfor 3 years. Prior to joining Egon ZehnderInternational Jane worked at Procter &Gamble in sales and then marketing inboth the US and Australia. Jane has anMBA from Harvard Business School and aBachelor of Arts from Smith College. MsAllen joined the Foundation Board in 2007.
Alec Brennan Alec Brennan pursues a portfolio ofbusiness and not for profit interests. UntilMarch 2007, he was CEO and ManagingDirector of CSR Limited. He is Chairman ofpublicly listed Emeco Limited, Chairmanand co-investor in privately owned PPILimited and Chairman of TomagoAluminium Pty Ltd. He is a Fellow of theSenate of Sydney University and Chair ofseveral of its committees. Mr Brennanjoined the Foundation Board in 2000 andstepped down in 2008.
Philip Marcus Clark AM
Originally trained in law and management,Philip Clark has led the successful growthand development of two of Australia’slargest law firms, Minter Ellison andMallesons Stephen Jaques as ManagingPartner and CEO. Mr Clark is a member ofthe JP Morgan Advisory Council, Chairmanof the Higher Education Endowment FundAdvisory Board and a director of INGManagement Ltd, CRI Asset ManagementLimited, M+K Lawyers Holdings Ltd, St
James Ethics Centre and two scholarshipfoundations. Mr Clark joined theFoundation Board in 2005 and steppeddown in 2008.
Melinda Conrad Melinda Conrad is former ManagingDirector and Founder of the retail storechain, Conrads Warehouse. Prior to herestablishment of Conrads, she heldmanagement roles at Harvard BusinessSchool and Colgate-Palmolive. Ms Conradis also a director of the AustralianBrandenburg Orchestra. Ms Conrad joinedthe Foundation Board in 2003.
Geoff DixonGeoff Dixon is on the Boards ofConsolidated Media Holdings Limited andCrown Limited. He is also Chairman of theRisk Committees of both ConsolidatedMedia Holdings and Crown Limited.
Mr Dixon stepped down in November2008 after eight years as ManagingDirector and Chief Executive Officer ofQantas Airways Limited. Mr Dixon joinedthe Foundation Board in 2008.
Garvan Research Foundation Board
Garvan Research Foundation was established in 1981 to provide the Garvan Institute with an additional sourceof research funds by attracting financial support from companies and individuals. Over the years, theFoundation has evolved to become Garvan's marketing, communications and fundraising arm.
The Foundation's Board is empowered as the governing body to determine the Foundation's policy and controlits affairs subject to the ultimate direction of the Garvan Institute Board.
Graham J Bradley
Jane Allen
Melinda Conrad
Geoff DixonPhilip Marcus Clark AM
Alec Brennan
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Gabriel FaragoGabriel Farago is a company director andconsultant advising corporations onlitigation management. Prior toestablishing his consultancy, he practisedas a solicitor and barrister for over 30years, specialising in commercial disputesboth in Australia and overseas. Mr Faragohas extensive business interests, and hasbeen involved in property developmentfor more than 20 years. A passion forphilanthropic and charitable causes alsoreaches back many years, and in 1984 he was made a member of the Knightly Order of Vitez. Mr Farago joined theFoundation Board in 2008.
Bill Ferris AC
Bill Ferris is Executive Chairman of theCHAMP Private Equity Group, one ofAustralia's leading private capital groups,providing venture capital, expansion capital and management buyout funding in Australasia. Mr Ferris is Chairman of theGarvan Institute of Medical Research andrecently appointed Chair of the Health andHospitals Fund Advisory Board as part ofthe Federal Government's Nation-BuildingFunds initiative. Former directorshipsinclude: Chairman, Australian TradeCommission (Austrade), Austar UnitedCommunications Limited and BradkenResources Pty Ltd.
Mr Ferris was made an Officer in theOrder of Australia in 1990 for services tothe export industry and in 2008 wasmade Companion in the Order of Australiafor his philanthropic activities and his rolein the establishment of the private equitysector in Australia.
Mary FoleyNominated by the Sisters of Charity
Mary Foley held the position of the ChiefExecutive Officer, St Vincents & MaterHealth Sydney until early 2008. Ms Foleyis currently the National Health PracticeLeader at PricewaterhouseCoopers.Previous positions include Deputy Head,NSW Department of Health and ExecutiveDirector, NSW Office of Health Policy andsenior executive management positionsfor Mayne Nickless private health carebusiness. Ms Foley is Deputy Chancellorand a member of the Board of Trustees,University of Western Sydney as well as a member of the Board of Governors ofUniversity of Notre Dame Australia. MsFoley was NSW Telstra Businesswoman of the Year in 1998 and was awarded theCentenary Medal in 2003 for service toAustralian society in business leadership.Ms Foley stepped down from the Boardsof the Garvan Institute and GarvanResearch Foundation in 2008.
Lyn Gearing Lyn Gearing was appointed to the GarvanFoundation Board in 2005 as arepresentative of the Sisters of Charity.Ms Gearing was a Director of StocklandCorporation Limited up until December2008 and is currently a Director ofQueensland Investment CorporationLimited, Hancock Natural Resource GroupAustralasia Pty Limited, IMB Limited andtwo other not for profit organisations. Ms Gearing was the CEO of the NSWState Superannuation schemes from 1997 to 2002, and has substantialexperience in superannuation, fundsmanagement, corporate finance andmanagement consulting. Ms Gearingjoined the Foundation Board in 2005.
Loftus Harris AM
Loftus Harris is a non-executive directoron boards in NSW, Victoria andQueensland, a national director of theAustralian Institute of Export, and holdsthe appointment of Special TradeRepresentative to the Middle East andIndia for the Queensland Government. He previously held chief executive positionsin the NSW and Queensland public sectorswith responsibility for whole-of-government activities including internationaltrade, investment, innovation, businessand regional development. He also servedextensively overseas as an AustralianTrade Commissioner. Mr Harris joined theFoundation Board in 2008.
Meredith Hellicar Meredith Hellicar is a company directorand consultant in strategy and change.She is Chairman of AMP Life and adirector of AMP Limited, AMP Bank,Amalgamated Holdings and the SydneyInstitute. She is a member of the AdvisoryBoard of the Marsh McLennan Group inAustralia and of the Board of Governors ofCEDA. Meredith was awarded a CentenaryMedal for Business Leadership. Her formerdirectorships include James HardieIndustries, HLA Envirosciences, SouthernCross Airports Group, NSW TreasuryCorporation, AurionGold, HCS Limited andthe NSW Environment Protection Authority.She was a member of the Takeovers Paneland the Foreign Affairs Council and herprevious executive roles include ManagingDirector of InTech Financial Services, ChiefExecutive Officer of Corrs ChambersWestgarth and Managing Director of TNTLogistics Asia. Ms Hellicar joined theFoundation Board in 2002.
Loftus Harris AM
Lyn Gearing Meredith HellicarBill Ferris AC
Mary FoleyGabriel Farago
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Byram Johnston OAM
Byram Johnston is the Chief ExecutiveOfficer of MainstreamBPO, a companyproviding back office processing andadministration services to fund managersand superannuation funds. Prior toestablishing this business he spent over30 years as a management consultant. He serves on the board of a number ofcompanies. Mr Johnston joined theFoundation Board in 1997.
Ross KingRoss King is a Managing Director atGoldman Sachs JBWere where he hasspent the last 16 years providinginvestment banking and financing advice.He has worked across numerous productareas including investment banking, equitysales and research and was made aPartner in 1994. He fulfilled senior roles in both the New York and London officesbefore returning to Sydney in 2001 asCo-Head of the Healthcare, Consumer &Industrial Divisions of the InvestmentBanking department. Ross now hasresponsibility for the Natural Resourcesdivision. Mr King joined the FoundationBoard in 2005 and stepped down in 2008.
John Koch John Koch is Chief Representative of theHong Kong based Forma Group ofCompanies, a former board member of StVincent's Hospital and Chair of its FinanceCommittee. He is also the former Chair ofWoods Cottage Foundation which assistsintellectually disabled young adults. He had a 32 year career with the CommonwealthBank assuming a range of domestic andinternational responsibilities. Mr Kochjoined the Foundation Board in 2000.
John Landerer AM
John Landerer is a solicitor specialising incorporate advisory work and is also aprofessional company director. He iscurrently Chairman of Goldsearch Limitedand other private companies. He hasserved as Chairman of the HomePurchase Assistance Authority and is onthe Board of Life Education Australia andthe Royal Institute for Deaf and BlindChildren as well as on the Boards ofvarious charitable institutions. Mr Landererwas appointed a Visiting Professor atMacquarie University in Business andCommercial Law and holds an honorarydoctorate from that University. He is alsoa Fellow of Sydney University. MrLanderer is a Member of the Order ofAustralia and a Commander of the MostExcellent Order of the British Empire. He is also a Commander in the Order of theStar of Italian Solidarity. Mr Landererjoined the Board in 2007.
Sister Paulina Pilkington RSC AM
Sister Paulina has a broad background inhealth policy formation, having been amember of the Hospitals and HealthServices Commission (Sax Commission)and Assistant Director General, NursingBranch, Federal Department of Health.Sister Paulina resigned from the GarvanInstitute Board in February 2000 and hasbeen a member of the Foundation Boardsince 1994.
Brad ReesBrad Rees is involved in a number ofcharitable, arts and educational interests.Until 2007, he was a managing directorand equity partner of the investmentbanking firm Goldman Sachs JBWere. Brad was with the firm for 23 years andworked in the Melbourne, Sydney andLondon offices providing financial andinvestment banking advice to corporationsand governments in Australia andoverseas. Mr Rees joined the FoundationBoard in 2008.
Steven RubicSteven Rubic was appointed CEO of StVincents & Mater Health Sydney in April2008. Prior to this he was ExecutiveDirector of St Vincent's Private Hospital aposition he held since 1997. He iscurrently a Board Member of SV&MHS,the Health Industry (Superannuation) Plan,the Garvan Research Foundation, amember of Australian Commission onSafety and Quality Health Care (PrivateHospital Sector Committee) and is a pastChairman of the NSW Private HospitalsAssociation. He has completed an MBAand is a fellow of the Australian Instituteof Company Directors.
Byram Johnston OAM
John Koch
John Landerer AM
Sister Paulina Pilkington RSC AM
Brad Rees
Steven RubicRoss King
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John Shine AO FAA
Professor Shine is Executive Director ofthe Garvan Institute of Medical Research,Professor of Medicine and Professor ofMolecular Biology at the University ofNSW. He is also the recent ex-Chairmanof the National Health and MedicalResearch Council, past president of theAustralian Genome Research Facility, and a past Vice President of the AustralianAcademy of Science. He is an Officer inthe Order of Australia and until 2007 was a Member of the Prime Minister's Science,Engineering and Innovation Council.
Ian SmithIan Smith was until recently ChiefExecutive of Yahoo!7. He has more than20 years experience as a companydirector and advisor in the advertising,marketing communications and mediaindustries. Prior to leading themanagement buyout of theCommunications Group in 2003, MrSmith spent five years in New York asPresident International of Bates Worldwide and Director of the publiclylisted Cordiant Communications PLC. Healso led the development of Cordiant'sglobal e-business consultancy, which now operates in most major marketsaround the world. Mr Smith has served on a number of government andphilanthropic advisory groups including the Whitney Museum in New York and the State Library of New South Wales. Mr Smith joined the Foundation Board in2005 and stepped down in 2008.
The Hon Warwick L Smith AM
Warwick Smith is Chairman of theAdvisory Board of Australian Capital Equitygroup of companies, as well as the ANZBank for NSW and the ACT, and ofE*TRADE Limited. Formerly, Warwick wasan Executive Director with MacquarieBank. In a 15 year Parliamentary career he served as a Federal GovernmentMinister and in a variety of public roles. Hewas Australia's first TelecommunicationsOmbudsman. Warwick has a strong focuson international affairs. He is Chair of theGlobal Foundation, Immediate Past Chairof the Australia China Business Council and Deputy Chair of the Asia Society ofAustralia. Mr Smith joined the FoundationBoard in 2007 and stepped down in 2008.
Karim TemsamaniKarim Temsamani manages Google'sdomestic business and strategicpartnerships in Australia and New Zealand.Karim joined Google from Fairfax Media,where he was most recently GroupDirector, Fairfax General Magazines(responsible for growing the profile andadvertising revenue of Fairfax's suite ofinserted magazines) and CommercialDirector for Newspapers (responsible foragency and group sales, trade marketingand business development). Prior to thishe was the publisher and Vice President ofWho Weekly at Time Inc South Pacific. Hehas previously served in a variety of seniorcapacities with Hachette, including thepositions of regional business publisher inHong Kong, associate publisher for Koreain Seoul, and managing director forHachette in Sydney. Mr Temsamani joinedthe Foundation Board in 2008.
Peter WadePeter Wade is currently a consultant to amajor financial services organisation and acompany director. Peter previously spentover 25 years providing investmentbanking and financial advice with JBWereand its current form, Goldman SachsJBWere; more recently he was withJPMorgan. He worked for nearly 15 yearsin Europe and the United States beforereturning to Australia. He is a Director ofMMC Contrarian Limited, an ASX listedcompany. Mr Wade joined the FoundationBoard in 2002 and stepped down in 2008.
Richard FE Warburton AO
Dick Warburton is currently Chairman ofthe Board of Taxation, Magellan FlagshipFund, and Tandou Limited. He is a directorof Citibank, Chairman of theCommonwealth Studies Conference and aMember of the Advisory Council of theCentre for Social Impact. Mr Warburton isa former Chairman and CEO of DuPontAustralia and New Zealand, whom he hadworked with for 30 years. Mr Warburtonjoined the Foundation Board in 1999 andstepped down in 2008.
The Hon Warwick L Smith AM
Ian Smith
Peter Wade
Karim Temsamani Richard FE Warburton AO
John Shine AO FAA
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PUBLICATIONS
Abdipranoto A, Wu S, Stayte S, Vissel B.The role of neurogenesis inneurodegenerative diseases and itsimplications for therapeutic development.CNS Neurol Disord Drug Targets 2008;7:187-210.
Achuthan A, Masendycz P, Lopez JA,Nguyen T, James DE, Sweet MJ, HamiltonJA, Scholz GM. Regulation of theendosomal SNARE protein syntaxin 7 bycolony-stimulating factor 1 inmacrophages. Mol Cell Biol 2008;28:6149-59.
Ahlborg HG, Nguyen ND, Center JR,Eisman JA, Nguyen TV. Incidence and riskfactors for low trauma fractures in menwith prostate cancer. Bone 2008;43:556-60.
Akerfeldt MC, Howes J, Chan JY, StevensVA, Boubenna N, McGuire HM, King C,Biden TJ, Laybutt DR. Cytokine-inducedbeta-cell death is independent ofendoplasmic reticulum stress signaling.Diabetes 2008; 57:3034-44.
American Association for Cancer ResearchHuman Epigenome Task Force; EuropeanUnion, Network of Excellence, ScientificAdvisory Board. Moving AHEAD with aninternational human epigenome project.Nature 2008; 454:711-5.
Anton SD, Martin CK, Redman L, York-Crowe E, Heilbronn LK, Han H, WilliamsonDA, Ravussin E. Psychosocial andbehavioral pre-treatment predictors ofweight loss outcomes. Eat Weight Disord
2008; 13:30-7.
Avery DT, Bryant VL, Ma CS, de WaalMalefyt R, Tangye SG. IL-21-inducedisotype switching to IgG and IgA byhuman naive B cells is differentiallyregulated by IL-4. J Immunol 2008;181:1767-79.
Avery DT, Ma CS, Bryant VL, Santner-Nanan B, Nanan R, Wong M, Fulcher DA,Cook MC, Tangye SG. STAT3 is requiredfor IL-21-induced secretion of IgE fromhuman naive B cells. Blood 2008;112:1784-93.
Bao Y, Lopez JA, James DE, Hunziker W.Snapin Interacts with the Exo70 Subunitof the Exocyst and Modulates GLUT4Trafficking. J Biol Chem 2008; 283:324-31.
Barton CA, Clark SJ, Hacker NF, O'BrienPM. Epigenetic markers of ovarian cancer.Adv Exp Med Biol 2008; 622:35-51.
Barton CA, Hacker NF, Clark SJ, O'BrienPM. DNA methylation changes in ovariancancer: implications for early diagnosis,prognosis and treatment. Gynecol Oncol
2008; 109:129-39.
Basten A. The evolution of clinicalimmunology and allergy in Australia.Immunol Cell Biol 2008; 86:16-21.
Basten A, Fazekas de St Groth B. Specialregulatory T-cell review: T-cell dependentsuppression revisited. Immunology 2008;123:33-9.
Bennett HL, Brummer T, Jeanes A, Yap AS, Daly RJ. Gab2 and Src co-operate inhuman mammary epithelial cells topromote growth factor independence and disruption of acinar morphogenesis.Oncogene 2008; 27:2693-704.
Biankin AV, Nguyen NQ, Merrett ND. Post-pancreatectomy management. Medical
Observer 2008:27-29.
Biden TJ, Schmitz-Peiffer C, Burchfield JG,Gurisik E, Cantley J, Mitchell CJ, CarpenterL. The diverse roles of protein kinase C inpancreatic beta-cell function. Biochem
Soc Trans 2008; 36:916-9.
Boey D, Lin S, Enriquez RF, Lee NJ, Slack K,Couzens M, Baldock PA, Herzog H,Sainsbury A. PYY transgenic mice areprotected against diet-induced andgenetic obesity. Neuropeptides 2008;42:19-30.
Bogaerts S, Douglas S, Corlette T, Pau H,Saunders D, McKay S, Oleskevich S.Microsurgical access for cell injection intothe mammalian cochlea. J Neurosci
Methods 2008; 168:156-63.
Bolton K, Segal D, McMillan J, Jowett J,Heilbronn L, Abberton K, Zimmet P,Chisholm D, Collier G, Walder K. Decorin isa secreted protein associated with obesityand type 2 diabetes. Int J Obes (Lond)
2008; 32:1113-21.
Bossen C, Cachero TG, Tardivel A, IngoldK, Willen L, Dobles M, Scott ML, MaquelinA, Belnoue E, Siegrist CA, Chevrier S,Acha-Orbea H, Leung H, Mackay F,Tschopp J, Schneider P. TACI, unlike BAFF-R, is solely activated by oligomeric BAFFand APRIL to support survival of activatedB cells and plasmablasts. Blood 2008;111:1004-12.
Boyman O, Ramsey C, Kim DM, Sprent J,Surh CD. IL-7/anti-IL-7 mAb complexesrestore T cell development and inducehomeostatic T Cell expansion withoutlymphopenia. J Immunol 2008;180:7265-75.
Bradbury RA, Samaras K. Antiretroviraltherapy and the human immunodeficiencyvirus--improved survival but at whatcost? Diabetes Obes Metab 2008;10:441-50.
Brink R, Phan TG, Paus D, Chan TD.Visualizing the effects of antigen affinityon T-dependent B-cell differentiation.Immunol Cell Biol 2008; 86:31-9.
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Brummer T, Larance M, Abreu MT, LyonsRJ, Timpson P, Emmerich CH, Fleuren ED,Lehrbach GM, Schramek D, Guilhaus M,James DE, Daly RJ. Phosphorylation-dependent binding of 14-3-3 terminatessignalling by the Gab2 docking protein.Embo J 2008; 27:2305-2316.
Burt MG, Gibney J, Hoffman DM, UmplebyAM, Ho KK. Relationship between GH-induced metabolic changes and changes inbody composition: a dose and time coursestudy in GH-deficient adults. Growth
Horm IGF Res 2008; 18:55-64.
Burt MG, Johannsson G, Umpleby AM,Chisholm DJ, Ho KK. Impact of growthhormone and dehydroepiandrosterone onprotein metabolism in glucocorticoid-treated patients. J Clin Endocrinol Metab
2008; 93:688-95.
Butt AJ. Review of "Tamoxifen and TRAILsynergistically induce apoptosis in breastcancer cells." Breast Cancer Online 2008;11:e4.
Butt AJ, Caldon CE, McNeil CM, SwarbrickA, Musgrove EA, Sutherland RL. Cell cyclemachinery: links with genesis andtreatment of breast cancer. Adv Exp Med
Biol 2008; 630:189-205.
Butt AJ, Sergio CM, Inman CK, AndersonLR, McNeil CM, Russell AJ, Nousch M,Preiss T, Biankin AV, Sutherland RL,Musgrove EA. The estrogen and c-Myctarget gene HSPC111 is over-expressedin breast cancer and associated with poorpatient outcome. Breast Cancer Res
2008; 10:R28.
Caldon CE, Lee CS, Sutherland RL,Musgrove EA. Wilms' tumor protein 1: anearly target of progestin regulation in T-47D breast cancer cells that modulatesproliferation and differentiation. Oncogene
2008; 27:126-38.
Caldon CE, Swarbrick A, Lee CS,Sutherland RL, Musgrove EA. The helix-loop-helix protein Id1 requires cyclin D1 to promote the proliferation of mammaryepithelial cell acini. Cancer Res 2008;68:3026-36.
Calmy A, Carey D, Mallon PW, Wand H,Law M, Cooper DA, Carr A. Early changesin adipokine levels and baseline limb fatmay predict HIV lipoatrophy over 2 yearsfollowing initiation of antiretroviral therapy.HIV Med 2008; 9:101-10.
Campbell LV. The thrifty gene hypothesis:maybe everyone is right? Int J Obes
(Lond) 2008; 32:723-4; author reply725-6.
Cao XR, Lill NL, Boase N, Shi PP, CroucherDR, Shan H, Qu J, Sweezer EM, Place T,Kirby PA, Daly RJ, Kumar S, Yang B. Nedd4controls animal growth by regulating IGF-1 signaling. Sci Signal 2008; 1:ra5.
Chaganti S, Ma CS, Bell AI, Croom-CarterD, Hislop AD, Tangye SG, Rickinson AB.Epstein-Barr virus persistence in theabsence of conventional memory B cells:IgM+IgD+CD27+ B cells harbor the virusin X-linked lymphoproliferative diseasepatients. Blood 2008; 112:672-9.
Chang DK, Merrett ND, Biankin AV.Improving outcomes for operablepancreatic cancer: is access to safersurgery the problem? J Gastroenterol
Hepatol 2008; 23:1036-45.
Chetcuti A, Adams LJ, Mitchell PB,Schofield PR. Microarray gene expressionprofiling of mouse brain mRNA in a modelof lithium treatment. Psychiatr Genet
2008; 18:64-72.
Christ D, Chin JW. Engineering Escherichiacoli heat-resistance by synthetic geneamplification. Protein Eng Des Sel 2008;21:121-5.
Clarke E, Rahman N, Page N, Rolph MS,Stewart GJ, Jones GJ. Functionalcharacterization of the atopy-associatedgene PHF11. J Allergy Clin Immunol
2008; 121:1148-1154 e3.
Colvin EK, Chang DK, Merrett ND, KenchJG, Biankin AV. Individualizing therapy forpancreatic cancer. J Gastroenterol Hepatol
2008; 23:1779-82.
Cooper WA, Kohonen-Corish MR, Chan C,Kwun SY, McCaughan B, Kennedy C,Sutherland RL, Lee CS. Prognosticsignificance of DNA repair proteins MLH1,MSH2 and MGMT expression in non-small-cell lung cancer and precursorlesions. Histopathology 2008; 52:613-22.
Cooper WA, Kohonen-Corish MR, ZhuangL, McCaughan B, Kennedy C, Screaton G,Sutherland RL, Lee CS. Role and prognosticsignificance of tumor necrosis factor-related apoptosis-inducing ligand deathreceptor DR5 in nonsmall-cell lung cancerand precursor lesions. Cancer 2008;113:135-42.
Croucher DR, Saunders DN, Lobov S,Ranson M. Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev
Cancer 2008; 8:535-45.
Czernichow S, Greenfield JR, Safar ME.Impact of abdominal adiposity oncardiovascular disease predictors: what isthe missing link? Am J Hypertens 2008;21:851.
Danaher RN, Loomes KM, Leonard BL,Whiting L, Hay DL, Xu LY, Kraegen EW,Phillips AR, Cooper GJ. Evidence that{alpha}-Calcitonin Gene-Related Peptide Isa Neurohormone that Controls SystemicLipid Availability and Utilization.Endocrinology 2008; 149:154-60.
Das A, Chang D, Biankin AV, Merrett ND.Pancreatitis following humanpapillomavirus vaccination. Med J Aust
2008; 189:178.
Dean B, Karl T, Pavey G, Boer S, Duffy L,Scarr E. Increased levels of serotonin 2Areceptors and serotonin transporter in theCNS of neuregulin 1 hypomorphic/mutantmice. Schizophr Res 2008; 99:341-9.
Deenick EK, Tangye SG. Immunology:Helpful T cells are sticky. Nature 2008;455:745-7.
Doyle KL, Karl T, Hort Y, Duffy L, Shine J,Herzog H. Y1 receptors are critical for theproliferation of adult mouse precursor cellsin the olfactory neuroepithelium. JNeurochem 2008; 105:641-52.
Duffy L, Cappas E, Scimone A, SchofieldPR, Karl T. Behavioral profile of aheterozygous mutant mouse model forEGF-like domain neuregulin 1. Behav
Neurosci 2008; 122:748-59.
Dufour FD, Baxter AG, Silveira PA.Interactions between B-lymphocytes andtype 1 NKT cells in autoimmune diabetes.J Immunotoxicol 2008; 5:249-57.
Duncan CE, Chetcuti AF, Schofield PR.Coregulation of genes in the mouse brainfollowing treatment with clozapine,haloperidol, or olanzapine implicatesaltered potassium channel subunitexpression in the mechanism ofantipsychotic drug action. Psychiatr Genet
2008; 18:226-39.
Eid JP, Martinez-Arias AM, Robertson H,Hime GR, Dziadek M. The DrosophilaSTIM1 orthologue, dSTIM, has roles in cellfate specification and tissue patterning.BMC Dev Biol 2008; 8:104.
Eisman JA. Osteoporosis prevention andtreatment in elderly men--a cost-effective strategy. Nat Clin Pract
Endocrinol Metab 2008; 4:198-9.
Eisman JA, Civitelli R, Adami S, CzerwinskiE, Recknor C, Prince R, Reginster JY, ZaidiM, Felsenberg D, Hughes C, Mairon N,Masanauskaite D, Reid DM, Delmas PD,Recker RR. Efficacy and tolerability ofintravenous ibandronate injections inpostmenopausal osteoporosis: 2-yearresults from the DIVA study. J Rheumatol
2008; 35:488-97.
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Elder GJ. Nephrotic syndrome: don't forgetthe bones! Nephrology (Carlton) 2008;13:43-4.
Famm K, Hansen L, Christ D, Winter G.Thermodynamically stable aggregation-resistant antibody domains throughdirected evolution. J Mol Biol 2008;376:926-31.
Frangioudakis G, Cooney GJ. Acuteelevation of circulating fatty acids impairsdownstream insulin signalling in rat skeletalmuscle in vivo independent of effects onstress signalling. J Endocrinol 2008;197:277-85.
Gardam S, Sierro F, Basten A, Mackay F,Brink R. TRAF2 and TRAF3 signal adaptersact cooperatively to control thematuration and survival signals deliveredto B cells by the BAFF receptor. Immunity
2008; 28:391-401.
Gatt JM, Kuan SA, Dobson-Stone C, PaulRH, Joffe RT, Kemp AH, Gordon E,Schofield PR, Williams LM. Associationbetween BDNF Val66Met polymorphismand trait depression is mediated via restingEEG alpha band activity. Biol Psychol
2008; 79:275-84.
Govers R, James DE, Coster AC. High-throughput analysis of the dynamics ofrecycling cell surface proteins. Methods
Mol Biol 2008; 440:129-46.
Greenfield JR, Campbell LV. Role of theautonomic nervous system andneuropeptides in the development ofobesity in humans: targets for therapy?Curr Pharm Des 2008; 14:1815-20.
Greenfield JR, Moore J, Hill D, Brenner P,Delprado W, Turner J, Taylor J, Campbell L,Wong LY. Cushing's syndrome canprecipitate diabetes but mask non-Hodgkin's lymphoma. Med J Aust 2008;188:262.
Grey ST. Regulating inflammation: The yingand yang of NF-kappaB activation.Immunol Cell Biol 2008; 86:299-300.
Groom J, Mackay F. B cells flying solo.Immunol Cell Biol 2008; 86:40-6.
Grunfeld C, Kotler DP, Arnett DK, FalutzJM, Haffner SM, Hruz P, Masur H, MeigsJB, Mulligan K, Reiss P, Samaras K.Contribution of metabolic andanthropometric abnormalities tocardiovascular disease risk factors.Circulation 2008; 118:e20-8.
Guerrero-Bosagna CM, Sabat P,Valdovinos FS, Valladares LE, Clark SJ.Epigenetic and phenotypic changes resultfrom a continuous pre and post nataldietary exposure to phytoestrogens in anexperimental population of mice. BMC
Physiol 2008; 8:17.
Harmer AR, Chisholm DJ, McKenna MJ,Hunter SK, Ruell PA, Naylor JM, MaxwellLJ, Flack JR. Sprint training increases muscleoxidative metabolism during high-intensityexercise in patients with type 1 diabetes.Diabetes Care 2008; 31:2097-102.
Heilbronn LK, Campbell LV. Adipose tissuemacrophages, low grade inflammation andinsulin resistance in human obesity. Curr
Pharm Design 2008; 14:1225-30.
Heiser PW, Cano DA, Landsman L, Kim GE,Kench JG, Klimstra DS, Taketo MM, BiankinAV, Hebrok M. Stabilization of beta-catenin induces pancreas tumor formation.Gastroenterology 2008; 135:1288-300.
Hill NJ, King C, Flodstrom-Tullberg M.Recent acquisitions on the genetic basis ofautoimmune disease. Front Biosci 2008;13:4838-51.
Hilton HN, Stanford PM, Harris J, OakesSR, Kaplan W, Daly RJ, Ormandy CJ. KIBRAinteracts with discoidin domain receptor 1to modulate collagen-induced signalling.Biochim Biophys Acta - Mol Cell Res
2008; 1783:383-93.
Hinshelwood RA, Clark SJ. Breast cancerepigenetics: normal human mammaryepithelial cells as a model system. J Mol
Med 2008; 86:1315-28.
Ho KK. Can a single growth hormone levelbe used to assess disease activity aftertreatment of acromegaly? Nat Clin Pract
Endocrinol Metab 2008; 4:74-5.
Ho KKY. Effect of gonadal steroids ongrowth hormone action. In: Web SM,Chanson P, editors. A Decade of HypoCCS:The Changing Face of Pituitary Disease.Bristol UK: BioScientifica LTD; 2008. p.129-142.
Ho LL, Kench JG, Handelsman DJ, SchefferGL, Stricker PD, Grygiel JG, Sutherland RL,Henshall SM, Allen JD, Horvath LG.Androgen regulation of multidrugresistance-associated protein 4(MRP4/ABCC4) in prostate cancer.Prostate 2008; 68:1421-9.
Hocking SL, Chisholm DJ, James DE.Studies of regional adipose transplantationreveal a unique and beneficial interactionbetween subcutaneous adipose tissue andthe intra-abdominal compartment.Diabetologia 2008; 51:900-2.
Hoehn KL, Hohnen-Behrens C, CederbergA, Wu LE, Turner N, Yuasa T, Ebina Y,James DE. IRS1-independent defectsdefine major nodes of insulin resistance.Cell Metab 2008; 7:421-33.
Hokfelt T, Stanic D, Sanford SD, Gatlin JC,Nilsson I, Paratcha G, Ledda F, Fetissov S,Lindfors C, Herzog H, Johansen JE, UbinkR, Pfenninger KH. NPY and itsinvolvement in axon guidance,neurogenesis, and feeding. Nutrition
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Hoy AJ, Turner N. New insight into themechanism by which acute physicalexercise ameliorates insulin resistance. J Physiol 2008; 586:2251-2.
Hubert FX, Kinkel SA, Webster KE, CannonP, Crewther PE, Proeitto AI, Wu L, HeathWR, Scott HS. A specific anti-Aireantibody reveals aire expression isrestricted to medullary thymic epithelialcells and not expressed in periphery. J Immunol 2008; 180:3824-32.
Karl T, Duffy L, Herzog H. Behaviouralprofile of a new mouse model for NPYdeficiency. Eur J Neurosci 2008; 28:173-80.
Karlstrom H, Brooks WS, Kwok JB, BroeGA, Kril JJ, McCann H, Halliday GM,Schofield PR. Variable phenotype ofAlzheimer's disease with spasticparaparesis. J Neurochem 2008;104:573-83.
Katsoulotos GP, Qi M, Qi JC, Tanaka K,Hughes WE, Molloy TJ, Adachi R, StevensRL, Krilis SA. The Diacylglycerol-dependent translocation of ras guaninenucleotide-releasing protein 4 inside ahuman mast cell line results in substantialphenotypic changes, including expressionof interleukin 13 receptor alpha2. J Biol
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Kebede M, Favaloro J, Gunton JE, LaybuttDR, Shaw M, Wong N, Fam BC, Aston-Mourney K, Rantzau C, Zulli A, Proietto J,Andrikopoulos S. Fructose-1,6-bisphosphatase overexpression inpancreatic beta-cells results in reducedinsulin secretion: a new mechanism forfat-induced impairment of beta-cellfunction. Diabetes 2008; 57:1887-95.
Kench JG, Cosman PH, Merrett ND,Biankin AV. Pathology and molecularbiology of intraductal papillary mucinousneoplasms. In: Lowy AM, Leach SD, PhilipPA, editors. Pancreatic Cancer. New York:Springer Verlag; 2008. p. 63-64.
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King C. T helper cell differentiation: IL-21and T helper cell differentiation: Jack of all trades? Immunol Cell Biol 2008;86:554-6.
King C, Tangye SG, Mackay CR. TFollicular Helper (T(FH)) Cells in Normaland Dysregulated Immune Responses.Annu Rev Immunol 2008; 26:741-66.
Kraegen EW, Cooney GJ. Free fatty acidsand skeletal muscle insulin resistance. Curr
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Kraegen EW, Cooney GJ, Turner N. Muscleinsulin resistance: a case of fatoverconsumption, not mitochondrialdysfunction. Proc Natl Acad Sci U S A
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Kwok JB, Loy CT, Hamilton G, Lau E,Hallupp M, Williams J, Owen MJ, Broe GA,Tang N, Lam L, Powell JF, Lovestone S,Schofield PR. Glycogen synthase kinase-3beta and tau genes interact inAlzheimer's disease. Ann Neurol 2008;64:446-54.
Larance M, Ramm G, James DE. TheGLUT4 Code. Mol Endocrinol 2008;22:226-33.
Larson-Meyer DE, Newcomer BR,Heilbronn LK, Volaufova J, Smith SR,Alfonso AJ, Lefevre M, Rood JC,Williamson DA, Ravussin E. Effect of 6-month calorie restriction and exercise onserum and liver lipids and markers of liverfunction. Obesity (Silver Spring) 2008;16:1355-62.
Lee H, Whitfeld PL, Mackay CR. Receptorsfor complement C5a. The importance ofC5aR and the enigmatic role of C5L2.Immunol Cell Biol 2008; 86:153-60.
Lee NJ, Enriquez RF, Boey D, Lin S, Slack K,Baldock PA, Herzog H, Sainsbury A.Synergistic attenuation of obesity by Y2-and Y4-receptor double knockout in ob/obmice. Nutrition 2008; 24:892-9.
Lee NJ, Wong IP, Baldock PA, Herzog H.Leptin as an endocrine signal in bone. Curr
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Lee P, Campbell LV. Diabetic ketoacidosis:the usual villain or a scapegoat? A novelcause of severe metabolic acidosis in type1 diabetes. Diabetes Care 2008; 31:e13.
Lee P, Greenfield JR, Campbell LV. "Mindthe gap" when managing ketoacidosis intype 1 diabetes. Diabetes Care 2008;31:e58.
Lee P, Jones GR, Center JR. Successfultreatment of adult cerebral salt wastingwith fludrocortisone. Arch Intern Med
2008; 168:325-6.
Lee P, Milliken S, Center JR.Hypocalcaemic cardiac failure post BMTsecondary to unrecognized vitamin Ddeficiency. Bone Marrow Transplant
2008; 42:363-4.
Lee P, Samaras K. Coeliac disease in anIndian patient: an important diagnosis toconsider. Med J Aust 2008; 189:336-7.
Leong RW, Nguyen NQ, Meredith CG, Al-Sohaily S, Kukic D, Delaney PM, Murr ER,Yong J, Merrett ND, Biankin AV. In vivoconfocal endomicroscopy in the diagnosisand evaluation of celiac disease.Gastroenterology 2008; 135:1870-6.
Li H, Heilbronn LK, Hu D, Poynten AM,Blackburn MA, Shirkhedkar DP, KaplanWH, Kriketos AD, Ye J, Chisholm DJ. Islet-1: a potentially important role for an isletcell gene in visceral fat. Obesity (Silver
Spring) 2008; 16:356-62.
Llado A, Timpson P, Vila de Muga S,Moreto J, Pol A, Grewal T, Daly RJ, EnrichC, Tebar F. Protein Kinase C{delta} andCalmodulin Regulate Epidermal GrowthFactor Receptor Recycling from EarlyEndosomes through Arp2/3 Complex andCortactin. Mol Biol Cell 2008; 19:17-29.
Lloret-Linares C, Greenfield JR,Czernichow S. Effect of weight-reducingagents on glycaemic parameters andprogression to Type 2 diabetes: a review.Diabet Med 2008; 25:1142-50.
Lobov S, Croucher DR, Saunders DN,Ranson M. Plasminogen activator inhibitortype 2 inhibits cell surface associatedtissue plasminogen activator in vitro:potential receptor interactions. Thromb
Haemost 2008; 100:319-29.
Lopez JA, Kwan EP, Xie L, He Y, James DE,Gaisano HY. The RalA GTPase Is a CentralRegulator of Insulin Exocytosis fromPancreatic Islet Beta Cells. J Biol Chem
2008; 283:17939-45.
Lovis P, Roggli E, Laybutt DR, Gattesco S,Yang JY, Widmann C, Abderrahmani A,Regazzi R. Alterations in microRNAexpression contribute to fatty acid-induced pancreatic beta-cell dysfunction.Diabetes 2008; 57:2728-36.
Luty AA, Kwok JB, Thompson EM,Blumbergs P, Brooks WS, Loy CT, Dobson-Stone C, Panegyres PK, Hecker J,Nicholson GA, Halliday GM, Schofield PR.Pedigree with frontotemporal lobardegeneration--motor neuron disease andTar DNA binding protein-43 positiveneuropathology: genetic linkage tochromosome 9. BMC Neurol 2008; 8:32.
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Ma CS, Chew GY, Simpson N, PriyadarshiA, Wong M, Grimbacher B, Fulcher DA,Tangye SG, Cook MC. Deficiency of Th17cells in hyper IgE syndrome due tomutations in STAT3. J Exp Med 2008;205:1551-7.
MacArthur DG, Seto JT, Chan S, QuinlanKG, Raftery JM, Turner N, Nicholson MD,Kee AJ, Hardeman EC, Gunning PW,Cooney GJ, Head SI, Yang N, North KN. An Actn3 knockout mouse providesmechanistic insights into the associationbetween alpha-actinin-3 deficiency andhuman athletic performance. Hum Mol
Genet 2008; 17:1076-86.
Mackay CR. Moving targets: cell migrationinhibitors as new anti-inflammatorytherapies. Nat Immunol 2008; 9:988-98.
Mackay F, Schneider P. TACI, an enigmaticBAFF/APRIL receptor, with newunappreciated biochemical and biologicalproperties. Cytokine Growth Factor Rev
2008; 19:263-76.
Mallon PW, Sedwell R, Rogers G, Nolan D,Unemori P, Hoy J, Samaras K, Kelleher A,Emery S, Cooper DA, Carr A. Effect ofRosiglitazone on Peroxisome Proliferator-Activated Receptor gamma GeneExpression in Human Adipose Tissue IsLimited by Antiretroviral Drug-InducedMitochondrial Dysfunction. J Infect Dis
2008; 198:1794-1803.
Marino E, Batten M, Groom J, Walters S,Liuwantara D, Mackay F, Grey ST.Marginal-zone B-cells of nonobesediabetic mice expand with diabetes onset,invade the pancreatic lymph nodes, andpresent autoantigen to diabetogenic T-cells. Diabetes 2008; 57:395-404.
Marino E, Grey ST. A new role for an oldplayer: do B cells unleash the self-reactiveCD8+ T cell storm necessary for thedevelopment of type 1 diabetes? JAutoimmun 2008; 31:301-5.
Meier C, Nguyen TV, Handelsman DJ,Schindler C, Kushnir MM, Rockwood AL,Meikle AW, Center JR, Eisman JA, SeibelMJ. Endogenous sex hormones andincident fracture risk in older men: thedubbo osteoporosis epidemiology study.Arch Intern Med 2008; 168:47-54.
Merrett ND, Cosman P, Biankin AV.Education of imaging. Hepatobiliary andpancreatic: iatrogenic hemobilia. JGastroenterol Hepatol 2008; 23:821.
Murphy NC, Scarlett CJ, Kench JG, SumEY, Segara D, Colvin EK, Susanto J,Cosman PH, Lee CS, Musgrove EA,Sutherland RL, Lindeman GJ, Henshall SM,Visvader JE, Biankin AV. Expression ofLMO4 and outcome in pancreatic ductaladenocarcinoma. Br J Cancer 2008;98:537-541.
Musgrove EA, Sergio CM, Anderson LR,Inman CK, McNeil CM, Alles MC,Gardiner-Garden M, Ormandy CJ, Butt AJ,Sutherland RL. Identification ofdownstream targets of estrogen and c-myc in breast cancer cells. Adv Exp Med
Biol 2008; 617:445-51.
Musgrove EA, Sergio CM, Loi S, Inman CK,Anderson LR, Alles MC, Pinese M, CaldonCE, Schutte J, Gardiner-Garden M,Ormandy CJ, McArthur G, Butt AJ,Sutherland RL. Identification of functionalnetworks of estrogen- and c-Myc-responsive genes and their relationship toresponse to tamoxifen therapy in breastcancer. PLoS ONE 2008; 3:e2987.
Nelson AE, Ho KK. A robust test forgrowth hormone doping--present statusand future prospects. Asian J Androl
2008; 10:416-25.
Nelson AE, Meinhardt U, Hansen JL,Walker IH, Stone G, Howe CJ, Leung KC,Seibel MJ, Baxter RC, Handelsman DJ,Kazlauskas R, Ho KK. Pharmacodynamicsof growth hormone abuse biomarkers andthe influence of gender and testosterone:a randomized double-blind placebo-controlled study in young recreationalathletes. J Clin Endocrinol Metab 2008;93:2213-22.
Ng Y, Ramm G, Lopez JA, James DE. Rapidactivation of Akt2 is sufficient tostimulate GLUT4 translocation in 3T3-L1adipocytes. Cell Metab 2008; 7:348-56.
Nguyen ND, Frost SA, Center JR, EismanJA, Nguyen TV. Development ofprognostic nomograms for individualizing5-year and 10-year fracture risks.Osteoporos Int 2008; 19:1431-44.
Nguyen NK, Sartori SB, Herzog H, Tasan R,Sperk G, Singewald N. Effect ofneuropeptide Y Y2 receptor deletion onemotional stress-induced neuronalactivation in mice. Synapse 2008;63:236-246.
Nguyen TV, Center JR, Eisman JA.Pharmacogenetics of osteoporosis andthe prospect of individualized prognosisand individualized therapy. Curr Opin
Endocrinol Diabetes Obes 2008;15:481-8.
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PUBLICATIONS 77
Nguyen TV, Nelson AE, Howe CJ, SeibelMJ, Baxter RC, Handelsman DJ, KazlauskasR, Ho KK. Within-subject variability andanalytic imprecision of insulinlike growthfactor axis and collagen markers:implications for clinical diagnosis and dopingtests. Clin Chem 2008; 54:1268-76.
Nossent JC, Lester S, Zahra D, MackayCR, Rischmueller M. Polymorphism in the5' regulatory region of the B-lymphocyteactivating factor gene is associated withthe Ro/La autoantibody response andserum BAFF levels in primary Sjogren'ssyndrome. Rheumatology (Oxford) 2008;47:1311-6.
O'Brien PM, Davies MJ, Scurry JP, SmithAN, Barton CA, Henderson MJ, SaundersDN, Gloss BS, Patterson KI, Clancy JL,Heinzelmann-Schwarz VA, Scolyer RA,Zeng Y, Williams ED, Scurr L, Defazio A,Quinn DI, Watts CK, Hacker NF, HenshallSM, Sutherland RL. The E3 ubiquitin ligaseEDD is an adverse prognostic factor forserous epithelial ovarian cancer andmodulates cisplatin resistance in vitro. Br J Cancer 2008; 98:1085-93.
Oakes SR, Naylor MJ, Asselin-Labat ML,Blazek KD, Gardiner-Garden M, Hilton HN,Kazlauskas M, Pritchard MA, Chodosh LA,Pfeffer PL, Lindeman GJ, Visvader JE,Ormandy CJ. The Ets transcription factorElf5 specifies mammary alveolar cell fate.Genes Dev 2008; 22:581-6.
Oakes SR, Rogers RL, Naylor MJ, OrmandyCJ. Prolactin regulation of mammary glanddevelopment. J Mammary Gland Biol
Neoplasia 2008; 13:13-28.
Ormandy CJ. Prolactin Receptor. Current
Biodata - Target Protein Database 2008.
Painsipp E, Herzog H, Holzer P. Implicationof neuropeptide-Y Y2 receptors in theeffects of immune stress on emotional,locomotor and social behavior of mice.Neuropharmacology 2008; 55:117-26.
Painsipp E, Wultsch T, Edelsbrunner ME,Tasan RO, Singewald N, Herzog H, HolzerP. Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4receptor knockout mice. Genes Brain
Behav 2008; 7:532-42.
Palendira U, Chinn R, Raza W, Piper K,Pratt G, Machado L, Bell A, Khan N, HislopAD, Steyn R, Rickinson AB, Buckley CD,Moss P. Selective accumulation of virus-specific CD8+ T cells with unique homingphenotype within the human bonemarrow. Blood 2008; 112:3293-302.
Pedersen DJ, Lessard SJ, Coffey VG,Churchley EG, Wootton AM, Ng T, WattMJ, Hawley JA. High rates of muscleglycogen resynthesis after exhaustiveexercise when carbohydrate is coingestedwith caffeine. J Appl Physiol 2008;105:7-13.
Petersen DC, Severi G, Hoang HN, PadillaEJ, Southey MC, English DR, Hopper JL,Giles GG, Hayes VM. No associationbetween common chemokine andchemokine receptor gene variants andprostate cancer risk. Cancer Epidemiol
Biomarkers Prev 2008; 17:3615-7.
Polkinghorne E, Lau Q, Cooney GJ,Kraegen EW, Cleasby ME. Local activationof the I{kappa}K-NF-{kappa}B pathway inmuscle does not cause insulin resistance.Am J Physiol Endocrinol Metab 2008;294:E316-E325.
Ramanathan P, Martin IC, Gardiner-Garden M, Thomson PC, Taylor RM,Ormandy CJ, Moran C, Williamson P.Transcriptome analysis identifies pathwaysassociated with enhanced maternalperformance in QSi5 mice. BMC
Genomics 2008; 9:197.
Ramsey C, Rubinstein MP, Kim DM, ChoJH, Sprent J, Surh CD. The lymphopenicenvironment of CD132 (commongamma-chain)-deficient hosts elicits rapidhomeostatic proliferation of naive T cellsvia IL-15. J Immunol 2008; 180:5320-6.
Rittirsch D, Flierl MA, Nadeau BA, Day DE,Huber-Lang M, Mackay CR, Zetoune FS,Gerard NP, Cianflone K, Kohl J, Gerard C,Sarma JV, Ward PA. Functional roles forC5a receptors in sepsis. Nat Med 2008;14:551-7.
Rosen DB, Cao W, Avery DT, Tangye SG,Liu YJ, Houchins JP, Lanier LL. Functionalconsequences of interactions betweenhuman NKR-P1A and its ligand LLT1expressed on activated dendritic cells andB cells. J Immunol 2008; 180:6508-17.
Sakko AJ, Butler MS, Byers S, Reinboth BJ,Stahl J, Kench JG, Horvath LG, SutherlandRL, Stricker PD, Henshall SM, Marshall VR,Tilley WD, Horsfall DJ, Ricciardelli C.Immunohistochemical level of unsulfatedchondroitin disaccharides in the cancerstroma is an independent predictor ofprostate cancer relapse. Cancer Epidemiol
Biomarkers Prev 2008; 17:2488-97.
Samaras K. Metabolic consequences andtherapeutic options in highly activeantiretroviral therapy in humanimmunodeficiency virus-1 infection. JAntimicrob Chemother 2008; 61:238-45.
Samra JS, Biankin AV, Merrett ND. Role ofendoscopic ultrasound in the managementof pancreatic lesions. ANZ J Surg 2008;78:315-6; author reply 316-7.
Sasaki Y, Calado DP, Derudder E, Zhang B,Shimizu Y, Mackay F, Nishikawa S,Rajewsky K, Schmidt-Supprian M. NIKoverexpression amplifies, whereas ablationof its TRAF3-binding domain replacesBAFF:BAFF-R-mediated survival signals inB cells. Proc Natl Acad Sci U S A 2008;105:10883-8.
Schmitz-Peiffer C, Biden TJ. Protein kinaseC function in muscle, liver, and beta-cellsand its therapeutic implications for type 2diabetes. Diabetes 2008; 57:1774-83.
Seng TJ, Currey N, Cooper WA, Lee CS,Chan C, Horvath L, Sutherland RL,Kennedy C, McCaughan B, Kohonen-Corish MR. DLEC1 and MLH1 promotermethylation are associated with poorprognosis in non-small cell lung carcinoma.Br J Cancer 2008; 99:375-82.
Severi G, Hayes VM, Tesoriero AA,Southey MC, Hoang HN, Padilla EJ, MorrisHA, English DR, Sutherland RL, Boyle P,Hopper JL, Giles GG. The rs743572common variant in the promoter ofCYP17A1 is not associated with prostatecancer risk or circulating hormonal levels.BJU Int 2008; 101:492-6.
Shum BO, Rolph MS, Sewell WA.Mechanisms in allergic airwayinflammation - lessons from studies in themouse. Expert Rev Mol Med 2008;10:e15.
Sims AM, Shephard N, Carter K, Doan T,Dowling A, Duncan EL, Eisman J, Jones G,Nicholson G, Prince R, Seeman E, ThomasG, Wass JA, Brown MA. Genetic analysesin a sample of individuals with high or lowBMD shows association with multiple Wntpathway genes. J Bone Miner Res 2008;23:499-506.
Sonderegger I, Kisielow J, Meier R, King C,Kopf M. IL-21 and IL-21R are notrequired for development of Th17 cellsand autoimmunity in vivo. Eur J Immunol
2008; 38:1833-8.
Sprent J, Cho JH. Self/non-selfdiscrimination and the problem of keepingT cells alive. Immunol Cell Biol 2008;86:54-6.
Sprent J, Cho JH, Boyman O, Surh CD. Tcell homeostasis. Immunol Cell Biol 2008;86:312-9.
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Stanic D, Paratcha G, Ledda F, Herzog H,Kopin AS, Hokfelt T. Peptidergic influenceson proliferation, migration, and placementof neural progenitors in the adult mouseforebrain. Proc Natl Acad Sci U S A 2008;105:3610-5.
Stockli J, Davey JR, Hohnen-Behrens C, Xu A, James DE, Ramm G. Regulation ofGlut4 Translocation by the RabgapAs160/Tbc1d4. Role of Phosphorylationand Membrane Association. Mol
Endocrinol 2008; 22:2703-2715.
Stone ML, Walker JL, Chisholm D, CraigME, Donaghue KC, Crock P, Anderson D,Verge CF. The addition of rosiglitazone toinsulin in adolescents with type 1 diabetesand poor glycaemic control: a randomized-controlled trial. Pediatr Diabetes 2008;9:326-34.
Styrkarsdottir U, Halldorsson BV,Gretarsdottir S, Gudbjartsson DF, WaltersGB, Ingvarsson T, Jonsdottir T,Saemundsdottir J, Center JR, Nguyen TV,Bagger Y, Gulcher JR, Eisman JA,Christiansen C, Sigurdsson G, Kong A,Thorsteinsdottir U, Stefansson K. Multiplegenetic loci for bone mineral density andfractures. N Engl J Med 2008;358:2355-65.
Su YC, Rolph MS, Hansbro NG, MackayCR, Sewell WA. Granulocyte-macrophagecolony-stimulating factor is required forbronchial eosinophilia in a murine model ofallergic airway inflammation. J Immunol
2008; 180:2600-7.
Sue N, Jack BH, Eaton SA, Pearson RC,Funnell AP, Turner J, Czolij R, Denyer G,Bao S, Molero-Navajas JC, Perkins A,Fujiwara Y, Orkin SH, Bell-Anderson K,Crossley M. Targeted disruption of thebasic Kruppel-like factor gene (Klf3)reveals a role in adipogenesis. Mol Cell Biol
2008; 28:3967-78.
Sutherland RL, Sergio CM, Anderson LR,Inman CK, Butt AJ, Musgrove EA.Estrogens, cell proliferation and breastcancer. In: Melmed S, Rochefort H,Chanson P, Christen Y, editors. Research
and Perspectives in Endocrine
Interactions: Hormonal Control of Cell
Cycle. Berlin Heidelberg: Springer-Verlag;2008. p. 123-138.
Suttor VP, Biankin AV, Chin WK, Chow C,Biankin SA, Merrett ND, Alrubaie A.Pancreatic anomaly with multipleendocrine neoplasia type 1: a case ofpancreas divisum and hemosuccuspancreaticus (santorinirrhage). Pancreas
2008; 36:314-5.
Swarbrick A. Review of: Tumour invasionand metastasis initiated by microRNA-10bin breast cancer. Breast Cancer Online
2008; 11.
Swarbrick A, Roy E, Allen T, Bishop JM. Id1cooperates with oncogenic Ras to inducemetastatic mammary carcinoma bysubversion of the cellular senescenceresponse. Proc Natl Acad Sci U S A 2008;105:5402-7.
Tan MJ, Ye JM, Turner N, Hohnen-BehrensC, Ke CQ, Tang CP, Chen T, Weiss HC,Gesing ER, Rowland A, James DE, Ye Y.Antidiabetic activities of triterpenoidsisolated from bitter melon associated withactivation of the AMPK pathway. Chem
Biol 2008; 15:263-73.
Tran BN, Nguyen ND, Eisman JA, NguyenTV. Association between LRP5polymorphism and bone mineral density: aBayesian meta-analysis. BMC Med Genet
2008; 9:55.
Trapp EG, Chisholm DJ, Freund J, BoutcherSH. The effects of high-intensityintermittent exercise training on fat lossand fasting insulin levels of young women.Int J Obes (Lond) 2008; 32:684-91.
Tumes DJ, Wong AC, Sewell WA, McCollSR, Connolly A, Dent LA. Differential ratesof apoptosis and recruitment limiteosinophil accumulation in the lungs ofasthma-resistant CBA/Ca mice. Mol
Immunol 2008; 45:3609-17.
Turner N, Heilbronn LK. Is mitochondrialdysfunction a cause of insulin resistance?Trends Endocrinol Metab 2008; 19:324-30.
Turner N, Li JY, Gosby A, To SW, Cheng Z,Miyoshi H, Taketo MM, Cooney GJ,Kraegen EW, James DE, Hu LH, Li J, YeJM. Berberine and its more biologicallyavailable derivative, dihydroberberine,inhibit mitochondrial respiratory complex I:a mechanism for the action of berberineto activate AMP-activated protein kinaseand improve insulin action. Diabetes 2008;57:1414-8.
van der Poorten D, Milner KL, Hui J,Hodge A, Trenell MI, Kench JG, London R,Peduto T, Chisholm DJ, George J. Visceralfat: a key mediator of steatohepatitis inmetabolic liver disease. Hepatology 2008;48:449-57.
Viardot A, Heilbronn LK, Herzog H,Gregersen S, Campbell LV. Abnormalpostprandial PYY response in insulinsensitive nondiabetic subjects with astrong family history of type 2 diabetes.Int J Obes (Lond) 2008; 32:943-8.
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PUBLICATIONS 79
Vince JE, Chau D, Callus B, Wong WW,Hawkins CJ, Schneider P, McKinlay M,Benetatos CA, Condon SM, Chunduru SK,Yeoh G, Brink R, Vaux DL, Silke J. TWEAK-FN14 signaling induces lysosomaldegradation of a cIAP1-TRAF2 complex tosensitize tumor cells to TNFalpha. J Cell
Biol 2008; 182:171-84.
Vogelzang A, King C. The modulatorycapacity of interleukin-21 in thepathogenesis of autoimmune disease.Front Biosci 2008; 13:5304-15.
Vogelzang A, McGuire HM, Yu D, Sprent J,Mackay CR, King C. A fundamental rolefor interleukin-21 in the generation of Tfollicular helper cells. Immunity 2008;29:127-37.
Wadley GD, Siebel AL, Cooney GJ,McConell GK, Wlodek ME, Owens JA.Uteroplacental insufficiency and reducinglitter size alters skeletal musclemitochondrial biogenesis in a sex-specificmanner in the adult rat. Am J Physiol
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Walsh JP, Attewell R, Stuckey BG, HooperMJ, Wark JD, Fletcher S, Ferrari V, EismanJA. Treatment of Paget's disease of bone:a survey of clinical practice in Australia.Bone 2008; 42:1219-25.
Wang Y, Dean JL, Millar EK, Tran TH,McNeil CM, Burd CJ, Henshall SM, UtamaFE, Witkiewicz A, Rui H, Sutherland RL,Knudsen KE, Knudsen ES. Cyclin D1b isaberrantly regulated in response totherapeutic challenge and promotesresistance to estrogen antagonists.Cancer Res 2008; 68:5628-38.
Watt MJ, van Denderen BJ, Castelli LA,Bruce CR, Hoy AJ, Kraegen EW, MacaulayL, Kemp BE. Adipose triglyceride lipaseregulation of skeletal muscle lipidmetabolism and insulin responsiveness.Mol Endocrinol 2008; 22:1200-12.
Wong IP, Zengin A, Herzog H, Baldock PA.Central regulation of bone mass. Semin
Cell Dev Biol 2008; 19:452-8.
Yazdi M, Ahnmark A, William-Olsson L,Snaith M, Turner N, Osla F, Wedin M,Asztely AK, Elmgren A, Bohlooly YM,Schreyer S, Linden D. The role ofmitochondrial glycerol-3-phosphateacyltransferase-1 in regulating lipid andglucose homeostasis in high-fat diet fedmice. Biochem Biophys Res Commun
2008; 369:1065-70.
Ye J, Kraegen T. Insulin resistance: centraland peripheral mechanisms. The 2007Stock Conference Report. Obes Rev
2008; 9:30-4.
Yip MF, Ramm G, Larance M, Hoehn KL,Wagner MC, Guilhaus M, James DE.CaMKII-mediated phosphorylation of themyosin motor Myo1c is required forinsulin-stimulated GLUT4 translocation inadipocytes. Cell Metab 2008; 8:384-98.
Youn DH, Royle G, Kolaj M, Vissel B, RandicM. Enhanced LTP of primary afferentneurotransmission in AMPA receptorGluR2-deficient mice. Pain 2008;136:158-67.
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FINANCIAL HIGHLIGHTS 81
FINANCIAL HIGHLIGHTS
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Garvan Institute of Medical Research
2004 2005 2006 2007 2008 Income Statement $'000 $'000 $'000 $'000 $'000
NHMRC Grants 9,244 12,080 13,832 16,682 18,695 Other Peer Reviewed Grants 6,222 6,865 8,184 8,530 9,159 Other Grants 481 200 655 1,068 4,811 NSW Government Grant 2,880 3,720 12,174 4,063 4,026 Commonwealth Government Grant - - 4,700 1,193 - Commercial Collaborations 1,269 2,043 4,091 2,714 1,289 Garvan Research Foundation 1,671 2,343 2,562 3,817 4,689 Other Income 2,579 2,774 2,916 3,543 4,050
Total Operating Income 24,346 30,025 49,114 41,610 46,719
Remuneration Costs 14,879 17,377 21,983 23,621 27,337 Research Expenditures* 4,935 4,571 5,879 7,640 9,377 Administration and Information Technology 2,394 2,931 3,913 3,771 5,331 Building and Scientific Operations 1,891 2,378 2,438 2,461 2,753
Total Operating Expenses 24,099 27,257 34,213 37,493 44,798
Building Asset Amortisation (1,171) (1,171) (1,171) (1,180) (1,189)Property, Plant and Equipment Depreciation (1,235) (2,178) (2,449) (2,433) (2,390)Transfer from/(to) Building Reserve 1,047 1,047 (1,353) 1,047 1,047 Endowment Grants 1,250 745 10,965 2,210 3,953 Endowment Earnings 463 1,011 2,181 2,589 1,700 Donations & Bequests direct to Endowment Fund - - - - 5,393 Unrealised loss on Endowment Fund Investments - - - - (7,407)
Net Income 601 2,222 23,074 6,350 3,028
Accumulated Surplus Brought Forward 1,486 922 308 9,914 11,109
Transfer from/(to) Research Program Reserve (583) (1,110) (107) (2,526) 380 Transfer from/(to) Endowment Reserve (582) (1,726) (11,809) (3,664) 1,847 Transfer from/(to) Infrastructure Expense Reserve - - (1,552) 1,035 207
Accumulated Surplus Carried Forward 922 308 9,914 11,109 16,571
*The figures in 2006 and 2007 have been adjusted to improve the comparability with 2008.
82 FINANCIAL HIGHLIGHTS
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Garvan Instititute of Medical Research
2004 2005 2006 2007 2008 Balance Sheet $'000 $'000 $'000 $'000 $'000
Current Assets 3,672 5,632 18,236 19,405 30,012 Property, Plant and Equipment 41,540 40,022 40,903 45,160 60,085 Investments at Market Value 9,903 11,630 20,536 26,008 16,441
Total Assets 55,115 57,284 79,675 90,573 106,538
Current Liabilities* 2,949 3,547 6,900 8,343 7,860 Provisions 2,061 2,457 3,069 3,042 3,545 Borrowings 6,000 6,000 - 4,179 18,144
Total Liabilities 11,010 12,004 9,969 15,564 29,549
Accumulated Surplus 922 308 9,914 11,109 16,571 Reserves 43,183 44,972 59,792 63,900 60,419
Total Net Funds 44,105 45,280 69,706 75,009 76,990
*The figures in 2006 and 2007 have been adjusted to improve the comparability with 2008.
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FINANCIAL HIGHLIGHTS 83
Garvan Research Foundation
2004 2005 2006 2007 2008 Statement of Funds $'000 $'000 $'000 $'000 $'000
Donations & Pledges 3,276 2,524 3,826 4,961 6,861 Events 263 266 332 409 105 Bequests 4 928 10,315 1,847 3,132 Interest and Other income 17 42 21 25 55
Total Income 3,560 3,760 14,494 7,242 10,153
Fundraising Expenses (642) (607) (1,018) (1,184) (1,114)
Public Awareness Program (56) (66) - - -
Net Funds Raised 2,862 3,087 13,476 6,058 9,039
Accumulated Funds Prior Years 189 130 129 78 109
Funds Available for Grants to Institute: 3,051 3,217 13,605 6,136 9,148
General Research 567 850 871 750 926 Specific Research 1,104 1,493 1,691 3,067 3,762 Endowment Funds 1,250 745 10,965 2,210 3,953
Total Grants 2,921 3,088 13,527 6,027 8,641
Accumulated Funds Carried Forward 130 129 78 109 507
Represented By:Assets 197 182 251 311 1,391 Liabilities (67) (53) (173) (202) (884)
Net Assets 130 129 78 109 507
84
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Garvan Institute of Medical Research384 Victoria Street Darlinghurst Sydney NSW 2010 Australia
T +61 2 9295 8100 F +61 2 9295 8101
www.garvan.org.au
Project Manager Alison HeatherDesign Jason McDonaldPhotography Penelope Clay
Published April 2009
Copies of the Annual Report can beobtained by contacting:
Gabriella O’[email protected] +61 2 9295 8120
