2008 Annual Report

GM-CSF

α βc GMR The Hanson Institute Proudly bringing together the best of South Australia’s medical research Postal address PO Box 14 Rundle Mall South Australia 5000

Street address Frome Road Adelaide South Australia 5000

Telephone (618) 8222 3033

Facsimile (618) 8222 3035 [email protected] www.hansoninstitute.sa.gov.au

ISSN 1446-7941

Cover See Highlights, page four THE HANSON INSTITUTE is dedicated to excellence in basic and clinical research on the campus of SA Pathology and Royal Adelaide Hospital. Its primary goals are to make fundamental biological and biomedical discoveries, to provide an environment and world-class facilities necessary for conducting research at an international level, and to establish the important linkage between basic scientists and clinicians, thus facilitating the full development and application of the therapeutic potential of basic science discoveries. The Hanson Institute INCORPORATING Centre for Cancer Research Centre for Bone and Joint Research Clinical Research Centre Centre for Neurological Diseases Centre for Biomedical Research

Proudly bringing together the best of South Australia’s medical research CONTENTS

3 SA Pathology Executive Director’s Report 4 Hanson Highlights 6 Director’s Report Research Themes 10 Cancer 18 Bone & Joint 23 Clinical 30 Neurological Diseases 33 Biomedical 40 Core Facilities 45 Membership 48 Publication 63 Research Grants 79 Patents 80 Research Ethics 81 Clinical Studies 85 Invited Presentations 90 Awards, Appointments and Accolades 94 Research staff – Hanson Institute and Affiliated Laboratories 98 Management and Administration 99 Contributors to the Hanson Institute 100 Research Fund Review 101 How to donate

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best of South Australia’s medical research SA Pathology Director’s Report

SA PATHOLOGY was formed by the State Government in 2008 to amalgamate the several State Government-run Pathology service providers. Unusually for a Pathology provider, SA Pathology also incorporates some very successful research groups including the Hanson Institute PROFESSOR RUTH SALOM and Centre of Cancer Biology based in the city, as well as others based at the Women’s and Children’s Hospital and other Health Units.

As will be clear from the Highlights and the detail in this report, the Hanson Institute is a world-class medical The Hanson Institute provides an We are working through this research organisation. Rather than environment and facilities within which complexity in order to retain and recapitulate the highlights captured in researchers employed by SA Pathology, enhance the successes while reducing this report, I want to emphasise the the Royal Adelaide Hospital, and the any unnecessary duplication. I am success of our researchers in capturing University of Adelaide can focus on looking for transparency in all our highly-competitive funding from their research with minimal decision-making processes. NHMRC and other Commonwealth “distraction” with administrative and schemes, in securing highly sought- infrastructure issues. Facilities range The main characteristics of research in after external Fellowships which in from a Proteomics facility to a SA Pathology are excellence, coupled many cases provide their salaries, in Research Secretariat that ensures with relevance to human health. The publishing their findings in the top grant applications conform with the strong association and in many cases international scientific and medical requirements of the funding bodies; co-localisation of researchers with journals, and in taking their research from an Intellectual Property and Pathologists and other clinicians is through to clinical trial and application. Commercialisation Office to a variety conducive to a “translational” approach These represent the key performance of tissue banks. The provision of such to research which attracts researchers indicators by which medical infrastructure is an essential foundation who want to have an impact on the researchers are evaluated, and our to every successful research study. health of the community. researchers are on a par with the best There remain a variety of groups in Australia and internationally. administrative requirements that I take this opportunity to express my researchers find frustrating; some of appreciation of current and past these are unavoidable and my staff are leadership of the Hanson Institute working to mitigate those that are who have built this excellent research within our control. facility, and to State Government, which has fostered and encouraged The close and synergistic integration its growth. of researchers from SA Pathology, the Royal Adelaide Hospital and Adelaide I am unreservedly proud to have such University within the Hanson buildings, a strong research organisation within together with similar synergistic SA Pathology. interactions that exist at other Health Units, makes for a degree of complexity Professor Ruth Salom in moulding together the research Director groups of SA Pathology. SA Pathology

3 Annual Report 2008 Highlights

HANSON INSTITUTE researchers were awarded a total ofa total $20.7 of million $20.7 millionby the Nationalby the National Health andHealth Medical Researchand Medical Council Research (NHMRC) Council to support(NHMRC) 36 to Project Grants commencingsupport 36 Project in 2009. GrantsThis significantcommencing increase in 2009. includes grantsThis significant awarded increaseto SA Pathology includes staffgrants including awarded Women’sto SA Pathology and Children’s staff including Hospital Women’s and Flinders and Medical CentreChildren’s sites. Hospital Professor and Angel Flinders Lopez Medical in collaboration Centre withsites. Professor Professor Michael Angel Lopez Parker in (Stcollaboration Vincent’s Institute with ofProfessor Medical Michael Research, Parker Melbourne) (St Vincent’s was awardedInstitute an NHMRCof Medical program Research, grant Melbourne) valued at $3.7was awardedmillion to supportan NHMRC cancer program research. grant valued at $3.7 million to support cancer research. PROFESSOR ANGEL LOPEZ

BIOSPECTRUM ASIA assessed that two of the three most promising biotechnology companies in Australia were founded on intellectual property generated from the Hanson Institute. Labtech Systems, commercialising the clinical microbiology instrument Microstreak and Mesoblast, the adult stem cell therapy company, were the two companies highlighted. Mesoblast was also recognised as a leading company in Asia in another issue of BioSpectrum Asia during 2008 which was dedicated to stem cell commercialisation.  OUR FRONT COVER features the molecular structure of the cell signalling receptor controlling blood cells which when damaged RESEARCH CONDUCTED by Professor can be responsible for a form of Nick Fazzalari and his team in the leukaemia. The structure was Bone and Joint Research Laboratory published in the highly has been named as one of the ’10 of prestigious science journal, Cell. the Best Research Projects’ by the The work was conducted by NHMRC in 2008. This work is Professor Angel Lopez and his investigating new procedures for colleagues in collaboration with Professor Michael Parker and the early diagnosis of osteoarthritis  which affects 1.6 million Australians colleagues from the St Vincent’s each year.  Medical Research Institute, Melbourne. Using X-ray crystallography the researchers

PROFESSOR NICK FAZZALARI developed the first 3-dimensional image of the receptor bound to its signalling molecule. 

4 Annual Report 2008 Hanson Institute Proudly bringing together the best of South Australia’s medical research

CONGRATULATIONS to Professor Howard Morris for his award as 2009 SA Bioscience Industry Leader from Bio Innovation SA for the achievements of the Hanson Institute and his leadership as Director. On accepting the award Professor Morris said “It recognises the work of our outstanding researchers and our support staff as well as our collaborations with universities and the wider bioscience community in South Australia.” 

HOWARD MORRIS

MOLECULES RESPONSIBLE for the epithelial- mesenchymal transition, which is an initiating event in cancer metastasis have been identified and published in the outstanding science journal Nature Cell Biology. The data were generated by Associate Professor Greg Goodall and Dr Yeesim Khew-Goodall and their teams creating considerable international interest. These molecules, known as microRNAs, are now being investigated in model cancer systems as well as in clinical cancer specimens. 

GREG GOODALL AND YEESIM KHEW-GOODALL

THE HANSON INSTITUTE was pleased to acknowledge the award of Officer in the Order of Australia to Professor Christopher Burrell in the 2008 Queen’s Birthday Honours. Chris received this award for service to medicine as a specialist in infectious diseases, particularly in the field of virology, and as an administrator and educator, in which his research enabled the development of the first diagnostic tools and vaccines for Hepatitis B. Chris also received the award for services to the community of South Australia through the establishment of the Coriole Music Festival of which he has been Co-Founder and Musical Director since 1999. 

CHRIS BURRELL

5 Annual Report 2008 Director’s Report

THE OLD Chinese proverb “A picture’s meaning can express ten thousand words” has been modified and become a cliché but remains as relevant for medical research as for any other activity. Taken together with the recent advances in imaging technologies and their applications to biology, we have opportunities to open a myriad of new avenues for investigating all the PROFESSOR HOWARD MORRIS intricacies of life in health and disease.

The Hanson Institute is pursuing a strategy to ensure South Australian medical researchers have access to the resolution instruments available at the and large animals (sheep and pigs). full range of the latest developments University of Adelaide’s Adelaide It is currently supporting research in imaging technology including high Microscopy facility. This 1174 microCT into spinal disc disease and cardiology. magnification for imaging sub-cellular is a workhorse for researchers These research areas of investigation and cellular structures through to the investigating cancer and bone disease will be expanded during the coming investigation of pre-clinical small and at the Hanson Institute increasing year. Other imaging equipment is large animal models of human disease. the quality and quantity of data while also installed including dual X-ray Many of these instruments have been markedly reducing time. Adelaide absorptiometry for measuring provided through collaborations has become the Australian centre for hard and soft tissue composition. between the three South Australian this microCT technology and as a Extra instrumentation is planned for universities and Bio Innovation SA’s consequence, many national researchers installation during 2009. AIBLabs network as well as the are establishing collaborations with magnificent generosity of the donors our researchers. to the Hanson Institute. The Large Animal Research and The commissioning of the ‘NanoZoomer’ Imaging Facility (LARIF), situated at was completed during the year the Gilles Plains Field Station of SA complementing our extensive array Pathology, was opened by the of microscopes. This instrument allows Honourable Paul Caica (Minister for researchers to increase the number of Science and Information Economy) in tissue sections to be analysed by more November. This facility currently offers than 100 fold. Technology is now the high standard technology of a 1.5 available to place tissue samples from Tesla magnetic resonance imaging 100 to 600 cancer patients on one glass (MRI) instrument suitable for humans The Hon Paul Caica opens LARIF. slide. The ‘NanoZoomer’, can capture high resolution images of 210 glass slides automatically in a single batch. These images provide a number of advantages over traditional microscopy delivering higher quality data in a fraction of the time.

The ‘Skyscan’ 1174 micro-computerised tomography (microCT) analyser was installed within the Hanson Institute to provide low-resolution images of the skeleton and soft tissues of small animals and complements two high-

6 Annual Report 2008 Hanson Institute Proudly bringing together the best of South Australia’s medical research

L>R Howard Morris, Brendon Kearney, Justin Beilby, Kevin Kelly and Graham Spurling at the 2008 Annual General Meeting.

DR MICHELE GRIMBALDESTON

LARIF is a joint venture with the to or greater than 6 which represents and discussed the importance of such University of Adelaide and University the top 5% of all medical research collaborations as that forged between of South Australia and has been funded journals. Research published in these the Hanson Institute and the University through the Federal Government’s journals will continue to attract future to maintain the international National Collaborative Research research grant funding from the very competitiveness of our research effort. Infrastructure Scheme (NCRIS) and competitive funding agencies such as the SA Government. the NHMRC. Once again more than Once again we are grateful for the two thirds of all Hanson Institute support of Beckman-Coulter DSL for The Year in Review publications appeared in the top 25% their generous support for the New Hanson Institute researchers continued of international medical journals. Investigator Awards. The New Basic to be most successful with grants Scientist Award for 2008 was presented awarded by the National Health and General Meeting to Dr Michele Grimbaldeston who is Medical Research Council (NHMRC), It was a great pleasure to host Head of the Mast Cell Laboratory the major medical research funding Professor Justin Beilby, Executive within the Division of Human body in Australia. A significant increase Director of the Faculty of Health Immunology. She has contributed on the value for last year amounting to Sciences at the University of Adelaide significant work on the regulation of a record $23.5 million was awarded in as our guest speaker for the Hanson the immune system within skin tissue 2008 for program and project grants Institute Annual Meeting. Professor associated with the allergic response and fellowships commencing in 2009. Beilby described the strengths of which has been published in A total of 36 projects were funded medical research in South Australia exceptional impact journals including where Hanson Institute researchers and the pressures for change both Nature Immunology. She is also were Chief Investigators. This increase nationally and within the state. exploring the clinical application of includes the contribution from SA He complimented the Hanson Institute this work in collaboration with Pathology researchers working at all researchers on their achievements clinicians of the RAH Allergy Clinic. sites. Congratulations go to Professor Angel Lopez (Hanson Institute) and Professor Michael Parker (St Vincent’s Medical Research Institute, Melbourne) for the award of an NHMRC Program Grant for 5 years commencing in 2010. Total value of Grants This is in addition to the NHMRC 0 $5M $10M $15M $20M $25M Program Grant awarded to Dr Michael Beard in collaboration with a number 08 $20,000,000 79 / 493 of national researchers and commenced 07 $16,000,000 67 / 429 in 2009.

06 $12,000,000 61 / 424 The number of research publications continued to increase with 492 05 $8,000,000 44 / 328 manuscripts published during 2008, 04 $3,000,000 42 / 320 a 15% increase over that published in 2007. Importantly 79 (16%) were 0 50 100 150 200 250 300 350 400 450 500 published in journals of outstanding Number of Publications quality with an Impact Factor equal Impact factor >=6 / Annual Total

7 Annual Report 2008 Hanson Institute Proudly bringing together the best of South Australia’s medical research

The 2008 Clinical Scientist Award was presented to Associate Professor Sandra Hodge of the Lung Research ASSOCIATE PROFESSOR PROFESSOR HEDDY ZOLA SANDRA HODGE Laboratory for her research conducted in collaboration with members of the Department of Thoracic Medicine, The Coming Year The Shine Young Review recommended Royal Adelaide Hospital. Her research 2009 will continue as a year of marked that the Hanson Institute be a node of into Chronic Obstructive Pulmonary change to public health administration the SAHMRI and we look forward to Disease (COPD) has made significant in South Australia with particular an active collaboration with this new contributions to our understanding of attention to medical research. The entity to ensure SA medical this condition and led to new concepts launch of SA Pathology on 1 July 2008 researchers have the best resources regarding its cause. Her work has been is providing opportunities for research to enhance their internationally published in the leading journal in the collaborations across the campuses of competitive work. field and she plays a major role in Flinders Medical Centre, Women’s and clinical trials to apply this new concept Children’s Hospital and the Royal The Royal Adelaide Hospital along to treatment of the human disease. Adelaide Hospital. Research within SA with all the CNAHS health units will Pathology is being reviewed under the undergo their ACHS EQuIP 4 The Best Publication Award for 2008 expert guidance of Professor Heddy accreditation audits during 2009. was presented to Associate Professor Zola appointed as Director of Research Importantly research is now one of Greg Goodall on behalf of PA Gregory, for SA Pathology. Professor Zola will the essential components of the audit. AG Bert, EL Paterson, SC Barry, review the role of research The Hanson Institute is responsible A Tsykin, G Farshid, MA Vadas, administration, research activity and for research administration at the Y Khew-Goodall for their manuscript research infrastructure and recommend RAH and as such is responsible for titled “The miR-200 family and miR-205 policies for SA Pathology in each of the preparation of all the EQuIP 4 regulate epithelial to mesenchymal these areas. During this review period audit documents in this area. We look transition by targeting ZEB1 and SIP1” the operation of the Hanson Institute forward to a successful outcome published in the journal Nature Cell Advisory Board has been suspended. in 2009. Biology. The paper described a I am most grateful for the demanding mechanism by which epithelial and and conscientious work conducted by I am most grateful for the excellent mesenchymal tissues transition from the Board’s Chair, Mr Graham Spurling service and support of the staff of the one form to the other which was found and Board Members Mr Kevin Kelly, Hanson Institute Administration to be relevant to human breast cancer. Ms Virginia Deegan, Professor Bik To including the Research Secretariat and Professor Brendon Kearney who and the Intellectual Property and played such an important role in Commercialisation Office. The overseeing the Hanson Institute during establishment of SA Pathology has its formative intial 5 years and the increased research activity exceptional success that it has enjoyed administered by the Hanson Institute during this period. by some 25%. This increase in workload is such that it has required The SA Government has adopted the the introduction of new procedures, recommendation of the Shine Young all of which have been accommodated Review into Medical Research including by our staff. We look forward to a most the establishment of an independent successful year in 2009 and further ASSOCIATE PROFESSOR GREG GOODALL SA Health and Medical Research interaction of researchers within SA Institute (SAHMRI). The assessment Pathology, the RAH campus and the of current medical research resources universities to improve the health of within SA continues to provide a our community. foundation for the considerable consultation that is taking place with regard to its governance, scope and interaction with institutions currently undertaking medical research. Professor Howard Morris Director

8 Annual Report 2008 The Hanson Institute Research Themes Cancer Bone & Joint Clinical Neurological Biomedical

Proudly bringing together the best of South Australia’s medical research Hanson Institute Research Themes

WHILE THE NUMBER of people diagnosed and dying with cancer in South Australia continues to increase it is encouraging that the number of cancer deaths per 100,000 of the population, when adjusted for age, has been decreasing for more than 10 years. Cancer is a disease predominantly affecting older people with more than 60% of cancers occurring in people 65 years or older. Very often we seem to be becoming more aware of cancer in our community and this is due to the fact that every year our families and friends are getting older. Cancer

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best CYTOKINE RECEPTOR LABORATORY of South Australia’s medical research

L>R Barbara McClure, Hayley Ramshaw, Lin Dai (Daisy), Frank Stomski, Jarrod Sandow, Anna Sapa, Rebecca Krake, Prof Angel Lopez, Tim Hercus, Mara Dottore, Smita Hiwase, Melanie Pudney

Much of the success with decreasing Identifying targets in the fight against This publication provides essential the age-adjusted death rate from cancer information for pharmaceutical research cancer has been achieved by identifying A myriad of growth factors and to progress development of such and executing successful public health cytokines regulate cell growth and they therapeutics. campaigns to change life styles. have been found to provide many sites Thus the campaigns to reduce smoking of pathology leading to uncontrolled cell Fibroblast Growth Factor (FGF) and its can be credited with the almost 25% growth and cancer. This area is a fertile cell surface receptor (FGFR) is another reduction in the diagnosis of lung area for cancer researchers. Each of such system regulating the survival and cancer and deaths from lung cancer these factors initiate their biological growth of fibroblast cells. Research by recorded amongst males over the last response through binding to a specific the Cell Growth and Differentiation 25 years. These gains are yet to be receptor usually located on the surface Laboratory has identified a new mode achieved for women. Increasing of the cell. The biological response is of signalling involving phosphorylation exercise and increasing fruit and then propagated through the cell by a at specific sites on the FGFR which vegetables in our diet are also variety of biochemical reactions, many provides a docking site for another considered to have contributed to involving the transfer of phosphate intracellular signalling protein and is decreasing the risk of cancer. Improved moieties from protein to protein. essential for the full activation of these medical and surgical procedures have pathways. This important work also contributed to decreasing the A major finding in this area was continues the identification of death rate. published in the highly prestigious intracellular mechanisms regulating cell journal Cell by researchers of the growth and was published in the high Unfortunately as our population ages, Cytokine Receptor Laboratory impact factor journal Molecular and some 250 extra people are diagnosed working in collaboration with colleagues Cellular Biology. The research has with cancer in South Australia each at the St.Vincent’s Institute of Medical identified a common mechanism year and there are approximately an Research in Melbourne. The involving the phosphorylation of a extra 50 deaths from cancer each year. granulocyte-macrophage colony number of intracellular proteins that Consequently our research effort stimulating factor (GM-CSF) is one exert a variety of effects on cell growth continues at an increased level to such cytokine. It controls the providing a potential target for a drug identify the various causes of cancer production and function of blood cells, to disrupt this phosphorylation step and and the means to nullify their effects. its regulation is disrupted in rheumatoid could be found to be useful as a cancer 2008 has been a year where significant arthritis and leukaemia, and it is used therapeutic. research findings have been reported as a therapeutic agent in other diseases. by our cancer researchers. Cancer These researchers identified the Discovery of cellular messengers involved research at the Hanson Institute molecular structure of the binding in cancer metastasis encompasses the full spectrum of between GM-CSF and the two sub-units Epithelial tumours (carcinomas) studies from basic biochemical of its cell surface receptor as account for more than 80% of tumours mechanisms that regulate cell growth, determined by X-ray crystallography. in humans. The vast majority of deaths changes to the genetic code, to human Thus the research provides a 3- are due to metastasis, which is the studies of anticancer drugs and their dimensional picture of this structure formation of secondary tumours at sites side effects. with information on the essential remote from the primary tumour. chemical bonds which if targeted Metastasis involves conversion of some can stabilise or disrupt the structure. tumour cells to an invasive, migratory In this way the activity of GM-CSF can form in a process known as epithelial to be controlled by potential therapeutic mesenchymal transition (EMT). agents targeting these bonds.

11 Annual Report 2008 Hanson Institute Proudly bringing together the best MOLECULAR REGULATION LABORATORY of South Australia’s medical research

L>R Joey Puccini, Sonia Shalini, Briony Davenport, Loretta Dorstyn, Hazel Dalton, Yew Ann Leong, Kristen Ho, Scott Townley, Sharad Kumar, Natasha Boase, Donna Denton, Saman Ebrahimi

Highly novel results from the Cytokine as the stroma. Verifying that these cells This protein binds to sphingosine kinase Research Laboratory working in have down-regulated miR-200 will within cells and increases its activity by collaboration with researchers of the establish whether loss of miR-200 3-fold. When EF1A was reduced in cells Cell Signalling Laboratory have found always, or occasionally, coincides with sphingosine kinase activity was that EMT is controlled by small genetic the EMT in colorectal tumours, significantly reduced. A second protein regulators known as microRNAs and providing further evidence that EMT that modulates sphingosine kinase identified that the levels of a particular and stromal invasion involves down- activity is protein phosphatase 2A family of microRNA molecules (miR- regulation of the microRNAs. (PP2A). These researchers have found 200) were reduced in cells receiving a that PP2A reduces activity by removing specific signal to pass through the EMT. Sphingosine kinase; a key to controlling a phosphate moiety from a specific site This work was published in the highly blood vessel permeability in cancer on the enzyme, serine 225. Their data prestigious journal Nature Cell Biology Other messenger molecules act within indicate that a subunit of PP2A binds to and has generated considerable the cell to propagate and amplify signals sphingosine kinase to function as an international interest. received from the blood. One of these endogenous regulator. Both these signals is sphingosine-1-phosphate (S-1- reports appeared in the Journal of MicroRNA molecules have only recently P) which is synthesised by sphingosine Biological Chemistry. been discovered to exert important kinase. S-1-P plays a vital role in the effects on living processes. They are development of cancer and Unraveling the regulation of cell-death relatively small molecules that can inflammation because it regulates many genes using the common fruit fly regulate the expression of particular cell functions involved in regulation of In the healthy body the number of cells genes and often reduce the expression cell survival and motility, angiogenesis, is kept relatively constant through cell of genes. The researchers found that and inflammatory responses. Studies in division and programmed cell death. the reduction in the levels of miR-200 the Molecular Signalling Laboratory The unregulated control of cell numbers molecules was necessary to induce the have identified an important role for within the body results in cancer. EMT and is an important step in tumour sphingosine kinase in regulating the Programmed cell death, known as progression. In current work, proof of permeability of endothelial cells that apoptosis, is responsible for the death principle experiments in mice are being provides the barrier function for blood of some 50 billion cells per day in the conducted to determine whether vessels. Loss of sphingosine kinase average adult human. Dysregulation of forcing the presence of this microRNA activity in mice resulted in leaky blood apoptosis results in uncontrolled cell in cancer cells blocks the progression of vessels, while increasing the activity of proliferation and cancer. The apoptotic the tumour to metastasis. A number of this enzyme reduced their leakiness. pathways are complex and highly models of breast cancer are being used This work was published in the regulated. Considerable research is and their results will consolidate the prestigious journal Blood. underway to identify the various factors evidence for a role of miR-200 in breast involved in these pathways in order to cancer metastasis. These results will Further work has been conducted identify specific factors responsible for provide a basis for the design of larger during 2008 to identify the molecular cancer as well as to identify potential scale investigations of microRNA family signals inside cells that control targets for cancer therapeutics. members as prognostic indicators or sphingosine kinase activity. This is an therapeutic prospects. important area of work as there is little Studies conducted in the Molecular information and the identity of Regulation Laboratory have made Colorectal tumours are also being intracellular proteins that interact with significant contributions to this field. investigated for loss of miR-200 in sphingosine kinase will provide During 2008, further information on the invasive regions of the tumour likely to potential targets for the design of processes required for the activation of have undergone EMT. In a proportion of therapeutic agents to modulate specific the caspase enzymes was published in tumours, mesenchymal-like cells can be disease processes. One such protein the key scientific journal in this field seen invading the adjacent area known was Elongation Factor 1A (EF1A). Cell Death and Differentiation.

12 Annual Report 2008 Hanson Institute Proudly bringing together the best CANCER of South Australia’s medical research

The activation of caspases is the Myeloid Leukaemia success rates with Identifying the mechanism of drug principal event in the execution of conventional treatment strategies have resistance in Chronic Myeloid Leukaemia apoptosis. This activation often occurs reached a plateau in the last decade, Chronic Myeloid Leukaemia is a through the caspase acting with itself with only incremental improvements malignant disease of the bone marrow to form a dimer or larger complex. and many patients still dying within characterised by the over-production of Much of this research is conducted 5 years. Thus Acute Myeloid Leukaemia white blood cells. The disease strikes in the fruit fly model as these insects places a significant burden on families people of all ages and is incurable contain similar molecules and pathways and resources across this state. except for the few patients who are as human cells. These current findings suitable for a bone marrow transplant demonstrate that similar to human Mutated forms of the FLT3 molecule and have an appropriately matched caspases, an initial cleavage of the fruit occur in 30% of Acute Myeloid donor. The expected duration of fly homologue is not essential for Leukaemia cases and there is survival is around four years with apoptosis and provides evidence for a considerable interest in understanding standard therapy. pathway that has not been described the contribution of FLT3 on the growth previously. and survival of Acute Myeloid More recently, imatinib, a drug that Leukaemia cells. Studies by the Acute targets the causative defect of Chronic The expression of apoptotic genes is Leukaemia Laboratory have found Myeloid Leukaemia known as the often regulated by hormones that act that levels of a critical growth BCR/ABL protein, has shown exciting through receptors inside cells. These regulatory protein Gadd45 are down- results in the clinic. BCR/ABL is the receptors are activated by the binding regulated in the presence of FLT3 and product of a chromosome abnormality of a small molecular weight hormone that the reduction in Gadd45 levels is in leukaemic cells, producing which allows the receptor complex to critical for the growth and survival of uncontrollable cell growth in the bone bind directly to DNA in the nucleus of the Acute Myeloid Leukaemia cells. marrow. The challenge for researchers cells to regulate these genes. Recent This link between these two molecules is to maximise the effectiveness of results from the Molecular Regulation defines a pathway that can potentially this new agent and to develop other Laboratory published in the very high be targeted in Acute Myeloid agents that specifically attack Chronic impact factor journal Journal of Cell Leukaemia cells with the FLT3 Myeloid Leukaemia cells. However, the Biology have further elucidated how mutations. Understanding of the altered development of resistance continues the timing of the expression of these growth-regulatory pathways in Acute to be an issue. genes is regulated. A novel cofactor Myeloid Leukaemia will improve the has been identified to be responsible. chances of developing targeted, highly How do these resistant cells arise? It binds to two specific proteins which effective, less toxic therapies. This work Studies are continuing on a subset of interact with DNA to form the was performed collaboratively with leukaemic cells which is believed to be chromosome and therefore suppresses Professor Thomas Gonda at the intrinsically less sensitive to the drug. the expression of these apoptotic genes. Diamantina Institute for Cancer, In the absence of the cofactor, gene Immunology and Metabolic Medicine If true, such cells may be a potential activation is enhanced resulting in (University of Queensland) and source of those responsible for relapse higher levels of the cell-death genes. published recently in the journal from imatinib. Recent studies from the Leukemia. Throughout 2008 a joint Melissa White Leukaemia Research Growth-regulatory pathway identified as research program focused on Laboratory have focussed on the a target in Acute Myeloid Leukaemia haematological diseases at the Hanson mechanism of drug response Leukaemia accounts for 2.5% of all Institute/SA Pathology and the Basil heterogeneity, and these results suggest deaths and 10.9% of cancer related Hetzel Institute/TQEH has been that patient variability of response is deaths in Australia and for many established. due to their cells showing differences in leukaemia subtypes the rate of ability to take up or pump out the drug. successful treatment is still lower than 20%. It was projected that approximately 3,000 people including over 200 children (0-14 years) were diagnosed with leukaemia in Australia Approximately 3,000 people including over during 2008. Acute Myeloid Leukaemia 200 children were diagnosed with leukaemia in is predominantly a disease of the elderly and is therefore increasing in incidence. Australia during 2008 There are few specific tools available for early screening and intervention so development of new therapies is essential. For most forms of Acute

13 Annual Report 2008 Hanson Institute Proudly bringing together the best CANCER of South Australia’s medical research

This finding may allow therapy to be Tissue bank is a treasure chest for future Appropriate T cell selection in the tailored to individuals to maximise studies on leukaemia thymus is necessary to protect effectiveness. By studying families with an inherited individuals from developing immune predisposition to specific reactions against their own tissues and Because patients vary in their response haematological malignancies, therefore developing an autoimmune to imatinib, there is a need to assess information can be gained on steps in disease. Mutations in the autoimmune the biological activity of the drug in early disease formation and on the regulator gene are associated with leukaemic cells before treatment progression of the disease. Thus studies a severe multi-organ autoimmune commences. Techniques continue to be of the genetics of even rare leukaemias syndrome. One publication in Blood developed by the laboratory to examine that occur in some families can identify identified that the breakdown of the intrinsic sensitivity of leukaemic important factors which may arise in tolerance with reduced levels of cells to imatinib action. Their work more common cancers. This work also autoimmune regulator gene is to improve and standardise these provides information on people at risk associated with impaired responses to techniques has provided international of developing leukaemia and lymphoma interferons, a well characterised family leadership for the field. The initial as well as being used for the optimal of immune cell regulators, in the pattern of response to imatinib of selection of bone marrow donors. thymus. An important publication in leukaemic cells when cultured in the the prestigious New England Journal laboratory is predictive of the response Haematologists from SA Pathology and of Medicine from a large group to therapy in the medium term. Royal Adelaide Hospital, in of collaborators identified that the collaboration with Hanson Institute tissue-specific autoantigen for Major international collaborations researchers, have collected samples hypoparathyroidism as a result of involve the assessment of second- of many types of haematological autoimmune polyendocrine syndrome generation drugs targeting BCR/ABL. malignancies for over 30 years. type 1 (APS-1) is a protein known Important publications in high impact Specimens have been ‘banked’ under as NALP5. Autoantibodies in patient factor journals Journal of Clinical appropriate conditions and importantly, sera for NALP1 are highly specific and Oncology, Blood and Leukemia the clinical progression of the disease may be diagnostic for this prominent have reported that such drugs have for each specimen has been accurately component of autoimmune demonstrated efficacy for the treatment recorded. This collection is the largest polyendocrine syndrome type 1. of Chronic Myeloid Leukaemia in in the southern hemisphere and patients who have previously been holds the key to a large amount of Disruption of the male hormone receptor resistant or intolerant to imatinib. information on the causes of leukaemias a potential therapy for prostate cancer These studies involve clinical and lymphoma. Many of the Hanson The most widely used diagnostic test researchers in Europe, North America, researchers have accessed this ‘bank’ for any cancer is the measurement of South America as well as Adelaide. of cancer cells to test the applicability prostate-specific antigen (PSA) in blood of their findings to human leukaemias. for prostate cancer. Its use is highly An important study to which members controversial with some prostate cancer of the Melissa White Leukaemia During 2007 Professor Hamish Scott advocacy groups supporting its use as Research Laboratory contributed in was recruited to lead the Molecular a screening test for men after the age collaboration with colleagues at the Pathology Research Laboratory. of 50 while medical specialists have renowned St Jude’s Children’s Research His research is largely focussed on opposed its introduction in this manner. Hospital, Memphis USA and other investigating the genetic lesions giving It would appear however that many centres was published in Nature. rise to haematological malignancies. General Practitioners request a PSA It reported on a subset of patients with He has established a large number of test on the basis of a request from Acute Lymphoblastic Anaemia in which collaborations with researchers and patients and the number of tests has the BCR-ABL1 is the defining lesion the “bank” of cancer tissues is a most risen dramatically particularly since just as in Chronic Myeloid Leukaemia. valuable resource. A recent study using 1994 when it received more publicity. The research identified that a gene this material has identified two new A recent analysis of the incidence of encoding a transcription factor, (Ikaros) mutations in the Janus-kinase-2 (JAK- prostate cancer, incidence of advanced was deleted in some 84% of patients. 2) gene, which codes for an enzyme cancer and deaths from prostate cancer These data suggest that mutations critical to regulating the growth of in NSW before and after 1994 provides resulting in a loss of Ikaros function are blood cells. some interesting data on the usefulness an important event in the development of performing large numbers of PSA of BCR-ABL1 in Acute Lymphoblastic A series of important papers on the tests. This work was published in the Anaemia. role of expression of the autoimmune Medical Journal of Australia from the regulator gene, AIRE in the thymus the NSW Cancer Institute in and autoimmune disease, have been collaboration with the Dame Roma published with collaborators in the Mitchell Cancer Research Laboratory United Kingdom, Europe and the and showed that although the incidence United States as well as Melbourne. of prostate cancer rose significantly

14 Annual Report 2008 Hanson Institute Proudly bringing together the best CANCER of South Australia’s medical research after 1994, the fall in the incidence of In half of all cancers there are The previous industrial use of asbestos advanced cancer at diagnosis and death mutations in p53, resulting in has led to Australia having the world’s from prostate cancer suggest that there alterations of the p53 protein that highest rates of mesothelioma. maybe a benefit from the wide use of drastically eliminates its functions. The investigation of these important this test. The authors point out that ANKRD11 is a novel protein identified conditions and the development of other explanations cannot be excluded. by researchers of the Breast Cancer novel therapies are the major focus Genetics Laboratory which interacts of the Lung Research Laboratory. The major stimulator of healthy and with the p53 protein and modulates its malignant prostate growth is the function. Of particular interest is the Their work has shown that COPD is androgen receptor following activation discovery that ANKRD11 can restore associated with an excess of by androgens such as testosterone. levels of normal function to the mutant programmed cell death (or apoptosis) Researchers from the Dame Roma p53 proteins that are found in a broad in some of the cells present in the Mitchell Cancer Research Laboratory spectrum of malignancies. This was a airway wall. Further, they have shown have identified that in many prostate collaborative study with a research that particular cells (macrophages) cancers the androgen receptor is group at University of Medicine and whose job it is to clear away the dead modified to increase its activity and Dentistry of New Jersey, USA, the material are malfunctioning, thus such modification can cause prostate results of which were published in the potentially leading to an accumulation cancer in a mouse model. Current Journal of Cell Science. This is a very of the dead material and a perpetuation research is aimed at understanding the exciting finding since it provides an of the inflammatory response. intracellular processing of the androgen approach to treat cancer by restoring These changes persist in established receptor and developing strategies to the normal function of p53. Currently COPD even after cessation of smoking. disrupt its processing as novel targets this finding is being explored in more Studies on the development of new for prostate cancer therapeutics. detail with the aim of identifying lead therapies for COPD have investigated A recent review published in Molecular compounds that can be developed as a conventional pharmaceutical with an Endocrinology identified that the therapeutic drugs. investigator-initiated trial of low dose androgen receptor forms a dimer with Azithromycin to improve macrophage itself following binding of the androgen, Previous studies by the group function. The results published in the which facilitates binding of the established that the loss of the high impact factor journal American androgen receptor to DNA at sites to CBFA2T3 protein was associated with Journal of Respiratory and Critical regulate specific genes as well as recruit the development of breast cancer. Medicine have confirmed that cofactors and machinery necessary for A novel protein, ZNF652, has now been improvements are achieved in the the genes to be activated. It is now identified that combines with CBFA2T3 function of these cells in patients. known that in order for the androgen to control molecular pathways crucial in Further, the group has discovered that receptor to dimerise it interacts with the prevention of cancer. These results a family of molecules known as that part of the receptor that is were published in the Journal of collectins may have an important role necessary for it to bind to DNA. Biological Chemistry and current in macrophage dysfunction in COPD, However dimerisation also requires research is aimed at further providing a new target for potential interaction at three other parts of the characterisation of the pathways therapies. This work has laid the receptor. Disruption of any of these controlled by the CBFA2T3/ZNF652 foundation for a collaborative research sites disrupts the ability of the complex. Elucidation and grant with four other centres to androgen receptor to stimulate cell understanding of such cancer pathways investigate the potential utility of growth. Thus therapeutics targeted at will provide new approaches to Azithromycin as a treatment in asthma. disrupting any one of these sites could diagnosis and treatment of breast This project received nearly $3 million potentially halt or slow the growth of cancer. This work has attracted dollars from the NHMRC for projects prostate cancers. international interest and collaborations commencing in 2009, the highest single with research groups in Germany and project grant awarded. The study will New approaches to the diagnosis and the USA have been initiated. recruit 400 patients including 100 from treatment of breast cancer Adelaide, over the next four years and The development of cancer requires Improving macrophage function helps has a high chance of improving the way complex and varied changes to the in the fight against lung disease asthma is managed. This development is genetic makeup of a normal cell. p53 is Malignancies affecting the lungs remain an excellent indication of the ability of one of the most important proteins for a major cause of mortality, while the group to translate laboratory-based regulating the growth of normal cells. smoking contributes to poor lung research into clinical application. Conversion of a normal cell into a health, leading to chronic bronchitis A second new NHMRC project grant cancer cell requires direct or indirect and emphysema (often collectively has been funded to investigate novel inactivation of the p53 protein. referred to as Chronic Obstructive therapies directed at macrophage Pulmonary Disease, COPD). function in COPD.

15 Annual Report 2008 Hanson Institute Proudly bringing together the best LUNG RESEARCH LABORATORY of South Australia’s medical research

L>R Violet Mukaro, Chien-Li Liew, Jessica Ahern, Kirsty Herewane, Hubertus Jersmann, Aruna Shivam, Mark Holmes, Stephanie Wong, Greg Hodge, Wei Xia, Sandra Hodge, Paul Reynolds

Here too, there is a high chance of Studies by the Gastroenterology The results of microarray experiments developing useful new approaches to Research Laboratory in collaboration have been published in three important treatment. with the discipline of Surgery at the international cancer journals University of Adelaide and RAH and Cancer Treatment Reviews, Cancer Mesothelioma has a very poor Department of Nursing and Midwifery, Chemotherapy and Pharmacology prognosis, with average survival after Flinders University, have found that a and International Journal of Cancer. diagnosis of less than 12 months even number of genes commonly associated with latest generation chemotherapy. with cancer are silenced by methylation Targeted therapies are a new class of The Lung Research Laboratory has in Barrett’s oesophagus. The study was treatment for cancer. The Mucositis been working on an exciting concept of designed to determine the stage in the Research Group has focussed on combining immune-based therapy and progression from Barrett’s oesophagus Trastuzumab, a monoclonal antibody viral therapy for this disease. In mouse to oesophageal adenocarcinoma when used in the treatment of breast cancer. models, the group has shown that methylation of key genes occurs. The A retrospective study of the immunotherapy led to complete results, published in Molecular Cancer, gastrointestinal side effects caused regression of established mesothelioma suggest that metaplastic Barrett’s by Trastuzumab showed that patients tumours in about 90% of mice treated. oesophagus is a highly abnormal tissue, receiving this treatment have the Whether complete cure has been more similar to cancer tissue than to potential to develop a range of achieved awaits longer term studies. the epithelium in a healthy oesophagus. gastrointestinal toxicities. Age and This work continues to be supported disease status of patients were by the Cancer Council of SA. Mucositis is an important medical identified as risk factors that increase complication of cancer treatment vulnerability of patients to Barret’s oesophagus is often the end affecting the entire gastrointestinal Trastuzumab-induced toxicity. result of oesophageal reflux following tract. Some common symptoms are a considerable period of irritation from mouth ulcers, nausea, vomiting and Cancer treatment such as radiotherapy the reflux of acidic stomach contents. diarrhoea. Between 40 and 100 per cent or cytotoxic chemotherapy that induces It is found in about 10% of patients with of all patients undergoing cancer damage to DNA of the tumour is the heartburn although it is impossible to treatment will develop some form of most common kind of cancer treatment. predict which of them will develop this mucositis. Currently we can only Researchers in the Experimental condition. The normal columnar cells of manage the symptoms once they arise. Therapeutics Laboratory are the lower oesophagus are transformed developing APOMAB® technology to into metaplastic cells considered to be Chemotherapy is known to cause improve cancer ‘theranosis’, which is pre-malignant and are associated with dynamic interactive molecular and therapy guided by diagnosis. The aim increased risk of oesophageal cancer. cellular events throughout the mucosa. of this technology is to serve an unmet The expression of many genes can be Recently microarray technology has medical need, to diagnose cell death silenced through the addition of a been utilised to examine these changes in cancers soon after commencement methyl group to particular nucleotides in gene expression. The Mucositis of treatment allowing oncologists to of DNA making up the chromatin of the Research Group is working on decide whether to continue useful cell’s nucleus. elucidating the relationship between treatment or to cease ineffective genes and the network of pathways treatment, thus sparing patients involved in the pathobiology of unnecessary toxicity. mucositis to better target treatment. The discovery of new drugs for the prevention of mucositis and biomarkers that predict risk of severe damage in patients undergoing cancer treatment are under investigation.

16 Annual Report 2008 Hanson Institute Proudly bringing together the best CANCER of South Australia’s medical research

Recent developments of this technology have established that APOMAB® preferentially detects cancers at a late stage of cell death, which is likely to be the stage that is most useful for clinical application. This work was undertaken in collaboration with RAH Department of Nuclear Medicine and SA Pathology Neuropathology Laboratory.

If cancer cell death can be detected as an early indicator of the response to DNA-damaging cancer treatment then the second part of cancer theranosis can be implemented which is the delivery of further APOMAB®-guided cancer treatment. In studies this year, it was found that radiation attached to APOMAB® was safer and more effective if given 24 hours after chemotherapy than if it was either given alone or at the same time as chemotherapy. Oncaidia Ltd has licensed APOMAB® technology for commercialisation and received the 2008 Asia Pacific Frost & Sullivan Technology Innovation Award in the field of Cancer Diagnosis and Therapies.

Collaboration is underway with scientists at the Ian Wark Research Institute, University of South Australia, to attach nanoparticles to APOMAB® allowing magnetic resonance imaging for more sensitive detection of cancer cell death. The nanoparticles can also be prepared with a shell to carry radiation and chemotherapy drugs for enhanced delivery of cancer treatment directly at the tumour site. This work has been published in the high-impact journal, Advanced Materials, and it was chosen for highlighting in Nature Publishing Group Asia Materials website (www.asia-materials.com), a new online journal that highlights the best research published in the field of materials science by researchers in the Asia- Pacific region.

17 Annual Report 2008 Hanson Institute Research Themes

THE CENTRE for Bone and Joint Research brings together clinicians and laboratory-based researchers in collaboration with national and international colleagues in the fields of orthopaedic research, arthritis research and in studies on metabolic bone diseases. This Centre was again highly successful in obtaining funds from NHMRC during the 2008 round of grant applications. Bone & Joint

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best BONE AND JOINT of South Australia’s medical research

Of major interest currently is the Researchers in the Mesenchymal crest cells. When grown under special contribution from the Hanson Institute Stem Cell Group and Regenerative conditions in the laboratory they into investigation of the osteocyte cell. Medicine Program are one of the only developed characteristics of neuronal This cell type represents the greatest groups internationally able to purify cells. It was found that in an animal number of cells in bone tissue but up MSCs directly from human tissue model these cells developed to look like to date has attracted limited attention. using a patented isolation protocol. and act like nerve cells. The authors It is the cell type that is considered to Current research seeks to improve propose that these dental pulp stem respond to mechanical loading and understanding of the genes regulating cells can provide a readily accessible unloading of bone and new information the proliferation and differentiation of source of exogenous stem or precursor implicates this cell type in regulating MSCs. This work is essential in order cells that have the potential for use bone formation and resorption. In the to manipulate and expand MSC in cell therapies to treat neurological latest round of NHMRC grants, Hanson populations in vitro for subsequent re- diseases. researchers were the first to be funded implantation for use as cellular therapy. for a project to investigate osteocyte The use of MSCs, whether from the How much Vitamin D is required for properties. This research is being patient’s own body or from another a healthy skeleton? undertaken by a number of laboratories donor, in combination with bio- In Australia a person is admitted to within the Hanson Institute working in compatible implant materials, would hospital with an osteoporotic fracture collaboration and it is likely that they provide a novel solution for the once every five to six minutes, with will make a considerable contribution treatment of bone, cartilage and dentin osteoporosis costing the Australian recognised internationally in this area. loss and repair, avoiding the use of health system eight billion dollars grafting tissues with all their associated annually in direct and indirect costs. Identifying genes involved in the difficulties. These MSCs are relatively Most of these costs are associated regulation and differentiation of stem well tolerated by the immune system with treatment for hip fractures. cells thus enhancing their clinical application Osteoporosis is a chronic disease that Mesenchymal stem cells (MSCs) are as a single preparation can be used on a many patients endure for several under intensive study as novel number of patients, although this area decades, during which time they will therapeutic agents with the potential is also under further investigation. suffer several acute fracture events. for repairing connective tissue defects The risk of subsequent fracture due to trauma or disease that normally MSCs under appropriate conditions in following a first osteoporotic fracture cannot undergo spontaneous healing. the laboratory can be modified to adopt is estimated to increase fourfold. These include non-healing of fractures, cardiomyocyte and vascular cell The most clinically important fracture the loosening of joint prostheses with characteristics. Preclinical studies with is that of the hip following which the bone loss and replacement of large bony animal models of cardiovascular disease probability of death in the first year and cartilage defects, and even the have demonstrated their capacity to is estimated at 10–20%, while regeneration of dentin/pulp complex in facilitate both myocardial repair and the approximately half of the survivors are teeth. They are all common and difficult development of new blood vessels in disabled and need help with activities of clinical problems. A major clinical issue the heart. A review of this work and the daily living or require long-term nursing for regenerating tissues using stem cells limited experience with clinical trials, care. The relative risk of mortality is is to be able to generate sufficient stem which was prepared by the members of estimated to be 60% higher in women cells for cell transplantation. Thus a this laboratory, was published in the with vertebral fracture than in women large number of MSCs need to be leading journal in the field Stem Cells. without vertebral fracture. In this light, expanded extensively outside the body it is clear that to prevent healthcare ie ex vivo to be able to use them as Recent work also published in Stem systems being overwhelmed by cases of a cellular therapy. However, a major Cells described how human adult dental elderly trauma, determined efforts are pitfall for ex vivo expansion is that pulp stem cells can differentiate into required to curb the rising prevalence MSCs exhibit a limited lifespan in cell types reminiscent of cranial neural of fragility fracture. culture and more importantly, the progeny of MSCs gradually lose their capacity to differentiate following continuous subculture. To obtain the full benefits of this type of cellular therapy it is critical to identify and isolate only those cell populations that In Australia a person is admitted to hospital have the potential of MSCs as they with an osteoporotic fracture once every five to exist in the body. six minutes, with osteoporosis costing the Australian health system eight billion dollars annually in direct and indirect costs

19 Annual Report 2008 Hanson Institute Proudly bringing together the best BONE CANCER RESEARCH LABORATORY of South Australia’s medical research

L>R Vasilios Liapis, Shelley Hay, Andreas Evdokiou, Agatha Labrinidis, Irene Zinonos

An adequate nutritional status of Furthermore a number of studies from In order to develop clinical treatments vitamin D and dietary calcium can various Australian cities including for this bone loss the Orthopaedic Bone significantly reduce the risk of hip Adelaide indicate that some 80 per Cell Biology Laboratory must first fractures; however a major factor cent of the population has a vitamin D answer the question as to what are the impeding the effective introduction status lower than this level. Thus these cellular and molecular mechanisms by of public health measures is the lack important results need further which this bone loss occurs and can it of data as to the level of vitamin D confirmation before a large public be prevented? In their research they required for a healthy skeleton. health campaign is proposed to have found two related molecules called significantly raise the vitamin D status TNF alpha and TWEAK that are greatly Measurement of the direct effects of of the Australian population. increased during inflammation and may vitamin D on the skeleton requires an be at least partly responsible for bone invasive bone biopsy and therefore The metabolism of vitamin D within loss that occurs in rheumatoid arthritis laboratory studies have been conducted bone cells is a new area of major or around orthopaedic prostheses which using rodent models. An important interest because it determines the form have begun to wear and release tiny publication from the Endocrine Bone of vitamin D required for bone health. polyethylene particles, thus stimulating Research Laboratory during 2008 Recent information from the Hanson inflammation. This work conducted in reported that optimal bone structure Institute and other laboratories indicate collaboration with scientists at the was not achieved until the blood 25- that bone cells have the capacity to Boston-based company, Biogen-Idec hydroxyvitamin D level, the body’s transform vitamin D into the biologically and with Professor Linda Bonewald at indicator of vitamin D status, was active form and to regulate bone cells to the University of Missouri in Kansas greater than 80 nmol/L. At levels of maintain the skeleton. In collaboration City, USA indicates that TNF alpha and vitamin D below this value increased with the Orthopaedic Bone Cell TWEAK reduce the ability of the bone numbers of bone resorbing cells were Biology Laboratory a critical review of forming cells, osteoblasts, to mature generated resulting in a loss of mineral bone cell metabolism of vitamin D was and to make bone. from bone and increased risk of published in the high impact factor fracture. The increased number of bone journal Molecular Aspects of Medicine. Results published in Osteoporosis resorbing cells was a product of Continuing collaboration on bone cells International indicate that the increased levels of the key stimulator with particular emphasis on osteocytes therapeutic agent strontium ranelate of bone resorption, RANKL. Current between these laboratories is underway which reduces the risk of fracture in research is now focused on how low with funding from NHMRC for two new osteoporosis promotes the maturation vitamin D levels increase RANKL levels. projects in 2009. Fruitful collaborations of osteoblasts and their bone forming continue with the University of ability. In addition, it may enhance their This critical value of 80 nmol/L of 25- Melbourne Department of Medicine conversion to osteocytes, the cells that hydroxyvitamin D required for optimal Austin Hospital and with the Cancer are found within the bony matrix, and bone health is consistent with some Epidemiology Centre of The Cancer are increasingly understood to be recommendations from the United Council Victoria. important for bone health. States and with patient results reported last year from the Hanson Institute. Bone loss increasing the risk of However it is higher than the current fractures may occur throughout the recommendation from Australian skeleton, such as in osteoporosis, or at clinical laboratories. particular sites in the skeleton, such as in bone cancers and bone loss around artificial joints.

20 Annual Report 2008 Hanson Institute Proudly bringing together the best BONE AND JOINT RESEARCH LABORATORY of South Australia’s medical research

L>R Shruti Shah, Miss Geetha Mohan, Duminda Kumarasinghe, Julia Kuliwaba, John Codrington, Lisa Barrie, Julia Humphries, Nick Fazzalari, Egon Perilli, Lena Truong, Chris Malec, Helen Tsangari, Peter Sutton-Smith, Ruth Zoehrer

TRAIL is a molecule with a remarkable Sclerostin regulates osteoblast Low back pain is a very common ability to kill tumour cells but does development and bone formation by complaint in our community often not affect normal, healthy cells. preventing canonical Wnt signalling, a arising from degeneration of the spinal Work conducted by the laboratory in complex network of proteins required discs. Studies conducted by the collaboration with scientists at to perform normal physiological Adelaide Centre for Spinal Research Genentech in San Francisco has utilised processes. Bone loading suppresses have measured the density of cells in Genentech’s reagent which has the local expression of sclerostin near well-preserved discs from adult lumbar ability to bind to the TRAIL receptors bone forming surfaces, suggesting that spines and compared them with discs on cancer cells and stimulate TRAIL this protein plays a central role in which exhibited damage. This work biological activity. It demonstrates a transducing mechanical signals into a was reported in the leading journal in remarkable ability to kill established bone formation response. Work by the the field, Spine, which found that the tumours in a mouse model of cancer in Bone and Joint Research Laboratory number of cells in a disc reduced with bone tissue. Cancers are particularly has developed immunostaining of aging and was reduced in the areas of difficult to treat once they become cancellous femoral bone from elderly damage within each disc. Furthermore resident in bone and these agents are individuals for sclerostin. This damage at the end-plates of the spinal capable of killing cancers that arise in technology provides the opportunity vertebrae also reduced cellularity by bone, such as multiple myeloma, as for mapping the expression of this impeding disc nutrition. well as cancer cells from breast and protein in bone tissue of patients with prostate, which migrate to and colonise osteoporotic fracture and osteoarthritis. Artificial discs, or disc prostheses, are bone. Further work is being conducted emerging as alternatives to spinal fusion with other new molecules, which have In collaboration with surgeons, for the treatment of symptomatic the potential to not only kill cancer cells clinicians and pathologists, the Bone degeneration of spinal discs. Preclinical in bone, but to directly prevent the and Joint Research Laboratory is also studies of such prostheses were bone loss, and the inhibition of bone mapping the presence of molecules conducted in the sheep model, the formation, caused by some cancer cells. signalling bone removal and bone results of which were published in These very exciting studies are being formation in human bone tissue from Spine during 2008. An important conducted in collaboration with groups patients with osteoporosis and finding was that after some 6 months in Cyprus and at Novartis, a multi- osteoarthritis. The results from these no significant evidence of inflammation national company based in Switzerland studies, published in the journal Bone, or other tissue response from particles and the USA. identified altered expression of a of the material used to manufacture the number of genes which regulate prostheses was evident in this model. Sclerostin; a potential treatment for osteoblast and osteoclast differentiation osteoporosis and function as well as an imbalance Fish oil beneficial in the fight against Pharmacological intervention for the between the formation of bone forming arthritis and heart disease treatment of osteoporosis has the cells and fat storage cells. This study Rheumatoid arthritis requires treatment potential to halve future fracture has provided new insight into how as soon as possible after diagnosis in a incidence. Sclerostin is being developed bone removal and bone formation are manner that aims for early remission as a pharmaceutical to treat contributing to the genesis and progress to minimise significant damage to osteoporosis. It is a secreted protein osteoporosis and osteoarthritis. bone and joint. produced almost exclusively by mature Future work will investigate the osteocytes, bone cells embedded in location of these signalling molecules the bone mineral. in the human bone microenvironment so as to enable the development of improved diagnostic techniques and more effective treatment protocols for individuals at risk of osteoporotic fragility fracture and osteoarthritis.

21 Annual Report 2008 Hanson Institute Proudly bringing together the best BONE AND JOINT of South Australia’s medical research

To this end clinicians, informed by research conducted by the Arthritis and Rheumatology Research Laboratory, have established the Early Arthritis Clinic together with a structured program for the use of drugs that are responsive to a patient’s disease activity.

These processes have provided closely- tracked treatments and outcomes which have benefited patients and provided tools for further clinical research projects enhancing the translation of knowledge between the research laboratory and clinic.

The medicinal use of fish oil is being studied in several clinical trials. Its efficacy and utility has been reviewed in a publication from this laboratory in the journal Rheumatic Disease Clinics of North America. The trials draw on longstanding laboratory research on the omega-3 fats contained in fish oil and dietary studies with healthy volunteers. A particular focus has been on the use of fish oil as a substitute for non-steroidal anti- inflammatory drugs, the latter conferring risk of heart problems on top of the increased risk associated with rheumatoid arthritis itself. This work reported that fish oil can decrease anti- inflammatory drug use and can cause biochemical changes expected to decrease the risk of heart disease. The linkage between rheumatoid arthritis and heart disease led to extending such studies to cardiac patients in order to examine the efficacy of fish oil in these patients. Research published in the American Journal of Cardiology conducted in collaboration with cardiologists of the Cardiovascular Research Centre demonstrated that dietary fish oil can stabilise the heart against experimentally induced irregular heart rhythms.

22 Annual Report 2008 Hanson Institute Research Themes

CLINICAL RESEARCH is designed to identify and evaluate safer and more effective treatments or medical devices in consenting patients or volunteers. This work includes clinical trials that are mainly conducted within the RAH but also in the wider community, as well as a significant body of work on the characterisation of factors which contribute to disease or ill health. Clinical

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best NERVE-GUT RESEARCH LABORATORY of South Australia’s medical research

L>R Marita Broberg, Montri Gururatsakul, Tracey O’Donnell, Jenny Persson, Amanda Page, Ashley Blackshaw, Richard Young, Melissa Moretta, Stuart Brierley, Joel Castro, Andrea Harrington, Nicole Isaacs, Nathan Procter, Bridgette Cheng, Chris Martin

Early detection of macronodular adrenal This work has been published in the Research supported by the CCRE hyperplasia: a disease that runs in international journal Clinical recognises that poor nutrition families Endocrinology. Importantly, their work underpins numerous chronic diseases The Endocrine and Metabolic Unit has led to many other groups from the including obesity, diabetes mellitus focuses on the hypothalamic-pituitary- NIH (USA), New Zealand, Australia, and functional dyspepsia, and is pivotal adrenal (HPA) axis in health and France, Germany and Korea, sending to health outcomes in the elderly and disease. This HPA axis and its principal samples to assist in their efforts to those who are critically unwell. hormonal product, cortisol, are involved find the genetic causes of AIMAH. The focus of the studies will extend the in regulation of metabolism, immune In collaboration with the Molecular knowledge of the interactions between function, and the cardiovascular and Pathology Division of SA Pathology, the types of food being eaten and neurocognitive responses to stress. a single-nucleotide based genome-wide gastrointestinal function. search has been commenced to find During 2008, Dr Gagliardi, a PhD the genetic cause, in collaboration with The Centre of 14 Investigators, 2 student and endocrinologist, headed bioinformaticians at the Walter and Postdoctoral Fellows, and 4 a study of the clinical, biochemical, Eliza Hall Institute, Melbourne. Postgraduate students is led by immunohistochemical and tumour Professor Michael Horowitz, Director genetic studies of three families that Other work includes studies of the of Endocrinology, School of Medicine, the unit have recently identified with frequency of occult adrenal disease University of Adelaide, and brings an uncommon form of adrenal disease, that may exacerbate diabetes and together leading researchers within ACTH-independent macronodular hypertension and a study of the effects the Endocrine Research Laboratory, adrenal hyperplasia (AIMAH). of circadian/stress modulated cortisol Nerve-Gut Research Laboratory, IN AIMAH, benign massive tumours infusion in Addisons’ disease. Gastroenterology at the Royal Adelaide form in the adrenal glands and secrete A report in Clinical Endocrinology Hospital, the Obesity Research Group adrenal hormones, in most cases demonstrated, for the first time, that a of the Hanson Institute and CSIRO cortisol, leading to the more serious new agent (pasireotide) for pituitary Human Nutrition. Cushing’s syndrome, which may go Cushing’s may produce hypoadrenalism undetected for many years as the initial adding evidence of its likely benefit for The CCRE in Nutritional Physiology, manifestations such as obesity and this disease. The unit has also been Interventions and Outcomes enables mood disturbance are common. engaged in the development of a the development of multidisciplinary, Ultimately, the Cushing’s syndrome national tumour database to study collaborative clinical research program becomes advanced and without surgical pituitary disease and monitor patient with a focus on translation of cure death invariably ensues due to outcomes, and a study of pregnancy physiological concepts to interventional overwhelming infection. The groups outcomes in Addison’s disease. strategies. The bench to bedside first discovered family was from South approach and a strong clinical Australia, and comprised the largest Multidisciplinary centre to study nutrition orientation of research within the kindred reported internationally. and chronic disease Centre, involving human volunteers and The unit have determined that AIMAH The NHMRC funded CCRE in patient groups will continue to generate is indeed a disorder which runs in Nutritional Physiology, Interventions outcomes of direct clinical and public families and that it is possible to detect and Outcomes was established in 2007 health relevance. the disease before serious health with the intention to recognise and consequences develop. reward successful clinical researchers, and expand their ability to produce high quality research, provide high quality clinical research training and translate their research findings into improved health outcomes.

24 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL of South Australia’s medical research

The focus areas of the CCRE include: The laboratory has just commenced a They are interested in the effects • Diabetes and gastrointestinal project where they are determining of different (i) dietary fatty acids; regulation of glycaemia whether the taste of fat is linked with (ii) chemical messengers called • Obesity (Obesity and fast food its ability to modulate gut function and endocannabinoids (which bind to the consumption; Obesity management in suppress energy intake. They have also same receptors as marijuana); and (iii) primary care; Long term effects of evaluated the effects of short-term how the proportions of the different lauric acid on energy intake in obese fasting on gut function and appetite and types of muscle fibres might be subjects; Long term efficacy and found that gastrointestinal function is important. The effect of obesity to safety of low-carbohydrate diets) modified by fasting in that it enhances cause insulin resistance varies the response of the gut to nutrients, according to muscle fibre type and the • Nutrition in elderly (Pharmacological suggesting increased gastrointestinal laboratory has demonstrated potential interventions; Behavioural and sensitivity. Taken together, their mechanisms by which this occurs, and psychosocial correlates and research suggests that modulation of how some fatty acids cause insulin interventions; Nutritional aspects of gut function involved in the resistance in muscle cells while others interventions) acute regulation of energy intake may do not. They have found that there are • Nutrition in critical illness (Long be a novel approach in preventing three types of receptors for term follow up of nutritional overweight and obesity. endocannabinoids in skeletal muscle outcomes in critical care; Modulation and that when one type of receptor of gut peptides; Optimising glycaemic Regulation of energy use by muscle (CB1) is blocked, the muscle cells control) is important in obesity take up more glucose. The studies are Approximately two thirds of adults and ongoing, aiming to determine the Gastrointestinal function and appetite a quarter of children and adolescents mechanisms of these effects and how regulation in Australia are overweight or obese. they might be manipulated to Obesity is a major health issue in our Apart from effects on quality of life, a advantage. The group published a society with approximately 60% of considerable proportion of the burden review of the endocannabinoid system people overweight and 30% obese. of chronic disease and associated costs in food intake and metabolic regulation Most drug treatments that are available and loss of productivity can be directly which was published in the high impact are not effective in the longer-term attributed to obesity. journal Current Opinion in and some have adverse effects. Lipidology. The research of the Endocrine The Obesity Research Group functions Research Laboratory centres on the across the Freemasons Foundation Clinical Research role of the gastrointestinal tract in the Centre for Men’s Health and the The clinical studies in collaboration regulation of appetite and energy NH&MRC funded Centre for Clinical with the Cardiovascular Research intake. The approach has been based Research Excellence in Nutritional Centre focus on the obesity in men. on the premise that the modulation of Physiology and Related Disease. The studies have shown that obesity gastrointestinal function by nutrients Research is undertaken at a basic, adversely affects the function of the may enable individuals to reduce energy clinical and population health level, heart and blood vessels, including the intake. To explore this hypothesis, a with a strong translational focus. blood vessels supplying the penis which number of studies were performed. are necessary to produce erections. In one study, they administered Basic Research Importantly they have demonstrated intravenously the gastrointestinal Skeletal muscle is a major site of energy that acute rapid weight loss can be hormone, cholecystokinin (CCK) which use. Obesity is associated with defects safely implemented using specially regulates appetite, and found an inverse in the way skeletal muscle metabolises formulated meal replacements and relationship between the stimulation fat and responds to insulin. The basic leads to improvement in cardiovascular of pressures in the lower stomach studies focus on understanding the and erectile function, testosterone (pylorus) and subsequent energy nature of these defects, why they occur, levels and sexual desire and in addition intake. In other studies, they and how they might be treated. diminishes troublesome lower urinary investigated the influence of the size tract symptoms. of the droplet of lipid emulsions on gut function and energy intake and found that the emulsion with the smallest droplet size was associated with greater fat digestion and exhibited the most pronounced effects on gut function and appetite suppression. Obesity is a major health issue in our society with approximately 60% of people overweight and 30% obese

25 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL of South Australia’s medical research

Ongoing studies (Healthy Weight for Identifying patients likely to relapse in The Clinical Unit participated in a Life Project) are being undertaken in acute myeloid leukaemia large number of clinical trials which obese men with type 2 diabetes mellitus Taking laboratory research findings into testifies to their vigorous contribution and cardiac failure, and are also clinical application leading to better to improve understanding of new comparing the effects of various dietary health is the ultimate aim of biomedical therapeutic agents in a collaborative approaches and omega 3 fatty acids. research. The co-localisation of fashion with colleagues all over the laboratory and clinical research has world. Two other studies, LIMIT and always been the strength of research TRP channels; a new target for the control HOPScotch, address the problem of on this campus. The Haematology of stomach pain obesity in pregnancy and children aged Department has achieved this through 3-9 years old respectively. HOPScotch several of its sections which include The Nerve-Gut Research Laboratory is a collaborative study with the Royal the chronic myeloid leukaemia group aims to improve treatment of digestive Children’s Hospital and the Murdoch (Professors Tim Hughes and Junia disease by identifying and Institute in Melbourne and aims to Melo), the myeloma group (A/Professor understanding the interactions between develop and implement web-based Andrew Zannettino) and the Clinical the nervous system and the software to deliver a novel model Research Unit. gastrointestinal (GI) tract and to of shared care for childhood obesity. promote translational research from Obesity in pregnancy is associated with The Haematology Clinical Research single cells through to patients. a far higher risk of complications for Unit includes the Haematopoiesis Several conditions would benefit from the mother and obesity for the child. Expansion Laboratory (headed by Dr treatments that modify signalling of LIMIT, which involved a group that Ian Lewis), the Therapeutic Products sensory information from the gut to includes Obstetrics, Psychology, and Facility and the Clinical Trial Unit. the brain. In functional gastrointestinal Paediatrics at the University of disorders, such as irritable bowel Adelaide, is enrolling 2400 overweight The Haematopoiesis Expansion syndrome, patients are hypersensitive and obese women prior to 20 weeks of Laboratory reported new ways of to the contents of the gut and its pregnancy and is aiming to ensure that categorising acute myeloid leukaemia movements. In reflux disease there are weight gain does not exceed 5kg during into different prognostic subgroups disordered reflexes from the stomach the pregnancy in the intervention as well as the use of mesenchymal to the lower oesophageal sphincter that group. The study has recently received stromal cells in treating graft versus allow backflow of stomach acid into the additional funding from the National host disease, a serious complication oesophagus. In diabetes, patients show Institutes of Health in the USA. following allogeneic haemopoietic stem exaggerated responses of the gut to cell transplantation. Their work led glucose in the diet, accompanied by Population Health to several publications in 2008, one in profound symptoms. The Obesity Research Group has also the American Journal of Clinical conducted studies of men in the Pathology, where they reported that The group is investigating signalling in Northwestern suburbs of Adelaide leukemia-associated phenotypes can be sensory pathways in several ways. where there is a very high prevalence detected by five-colour multiparameter Firstly, the release of mediators such as of obesity-related chronic disease. flow cytometry which will enable them cytokines from immune cells and how They have shown that a range of social, to identify patients with high risk of this may be altered in patients with demographic and behavioural factors relapse into acute myeloid leukemia. functional gastrointestinal disorders; impact on changes to normal body secondly, the direct action of mediators composition that occurs with increasing The Therapeutic Products Facility and nutrients on sensory nerve endings; age resulting in obesity. In 2008, in provided the laboratory support thirdly, the function of the nerve ending collaboration with the University of for the haemopoietic stem cell and how it is modulated by receptors, Sydney, the group published in the transplantation of the Royal Adelaide ion channels and signal transduction important journal, American Journal Hospital. It hosts one of the largest pathways; and fourthly, the actions of of Clinical Nutrition, an article on leukaemia cell banks for research in transmitters released by sensory nerves lifestyle factors associated with age- Australia. It manufactures autologous from their endings within the brain and related differences in body composition. fibrin glue and autologous serum spinal cord. These different levels tears for patient use. A number of of investigation are consolidated in regenerative medicine projects are studies of function in animal models of also in development which we hope functional gastrointestinal disorders and to report next year. reflux disease.

26 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL of South Australia’s medical research

It is emerging through these Clinical studies evaluating the long-term Important clinical studies in the area translational research projects that outcome following joint replacement of joint replacement initiated in 2008 altered responses of peripheral blood The internationally recognised include evaluation of the treatment cells to immune challenge in patients Orthopaedic and Trauma Research methods for fractures that occur around with functional gastrointestinal Unit includes the Quality Assurance hip replacement prostheses; a clinical disorders may be a mechanism for and Research Unit, the Joint trial to examine the benefits of a new generation of their symptoms. Replacement and Joint Reconstruction tantalum trabecular metal acetabular Also drugs reducing sensitivity of Unit, the Musculoskeletal Imaging and prostheses to improve fixation after stomach sensory nerves may help in Analysis Unit, the Mechanical Testing primary total hip replacement; a the prevention of gastro-oesophageal Facility and the Implant Retrieval and comprehensive study examining how reflux in patients with reflux disease. Histological Analysis Laboratory. hip tendons that control hip function heal after hip replacement surgery; and In 2008, they continued studies on the The main research activities of the Unit how poor healing may influence hip role of specialised pores, known as include instability, which is a complication of transient receptor potential channels • long-term studies evaluating doctor hip replacement. (TRPs) in sensory nerves, and found important and patient-important they are important in transducing outcomes of elective and emergency The clinical trials program in the Unit mechanical force into biological energy. orthopaedic and trauma procedures was enhanced with the enrollment of They demonstrated that TRPV4 ion to inform evidence based clinical the Unit into multi-centre studies channels contribute to mechanically practice examining the role of bone evoked visceral pain which is an • randomised controlled trials in joint morphogenic protein in fracture healing important finding as it may present replacement and fracture of the humerus, the femur and the tibia. a selective novel target for the management The Unit also supported a review of the reduction of this pain in the absence • monitoring to determine best methods of treatment and the outcomes of current treatments. This work was practice management of of acute knee dislocation to drive published in the prestigious journal complications of joint replacement, refinements of clinical protocols for this Gastroenterology. A large collaborative and in particular bone loss, joint challenging injury. Researchers have study headed by Professor Gerald instability and infection also assisted trauma surgeons in a study Holtmann began investigating how • pre-clinical studies incorporating examining return to form following changes in gut function affect nutrition biomechanical evaluation and anterior cruciate ligament injury in elite in acutely ill patients. Professor histological analyses to examine new Australian Rules Football players. Holtmann was also successful in implant devices, surgical techniques This study showed that, on average, the award of one of the new and biomaterials to investigate their elite footballers do not return to their Complementary and Alternative potential for use in humans. pre-injury form following anterior Medicine Grants from NHMRC which cruciate ligament injury, which occurs will investigate the benefits of a herbal In 2008 the Unit had ongoing, and in nearly five percent of players. preparation in gut disorders. This also initiated new, randomised clinical This, and the high occurrence of re- involves a wide collaboration with trials in primary and revision joint injury, highlights the career-threatening primary care and public health replacement. For example, a current nature of this injury. The result of this economics. The laboratory also began international multi-centre randomised study, presented overseas to sports work on discovering why some patients controlled trial, coordinated by this injury conferences, has potential do not experience gut symptoms, even Unit, is examining dislocation following implications for how players are though they have life-threatening primary and revision hip replacement. managed after injury. disease. Finally, they began a Dislocation of the hip is one of the most collaboration with the Women’s and common early complications following With their prospective joint Children’s Hospital to determine some hip replacement surgery that requires replacement outcomes program now of the fundamental triggers for gastro- readmission to hospital and, in some operating for 23 years, the Unit oesophageal reflux episodes which may instances, further hip replacement continues to benchmark their hip and hold the key for improving treatment surgery. This problem represents a knee replacement surgery results of this common disease. significant health cost and impacts against the National Joint Replacement markedly on patient quality of life. population registry and the best results This study is being undertaken to in the international literature. determine whether dislocation can be These comparisons show that their reduced by the use of large diameter results are as good as, or better than, hip articulations, and is of international national and international best results. significance. This study is one of the largest randomised trials of joint replacement ever undertaken and involves over ten hospitals in the UK and Australia.

27 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL of South Australia’s medical research

The Orthopaedic Patient Management associated vasculitis, with Rituximab Their use in burn hypo-pigmentation and Outcomes Documentation and Mycophenolate Mofetil; and how will continue contingent on the (OPMOD) program and database, to determine the effect of changing to successful re-pigmentation of a test supported by the Royal Adelaide a sirolimus-based immunosuppression patch. This work is dedicated to Hospital, is managed by staff of the regime on the rate of development the memory of the project’s chief Quality Assurance and Research Unit of skin cancers in renal transplant investigator, Dr Christopher Back, who and continues to provide an essential recipients. An Australian and New tragically succumbed to a glioblastoma resource for patient unit record Zealand study was also conducted to multiforme (aged 32) in 2007. documentation and discharge reporting, determine the effect of an early start clinical auditing and clinical research. of dialysis. The laboratory, in collaboration with The other important resources available PolyNovo Biomaterials Pty (Melbourne, are the radiology services offered by Testing skin regeneration products for Australia), has been developing a the Department of Radiology and burns patients number of wound healing products Radiology SA. The Skin Engineering Laboratory is including the Biodegradable the research arm of the Burns Unit, Temporising Matrix (BTM). BTM is a Considerable advances have been made RAH, focused on developing a range of thin, flexible but strong polyurethane- in the research program during 2008 innovative skin regeneration products based mesh-like material designed to: in developing and evaluating an X-ray which will reduce or abolish the need i) stabilise the debrided wound bed and technique, dynamically loaded for autologous split-skin grafts in the ii) act as a scaffold for the generation of radiostereometric analysis, to monitor treatment of burns as well as in skin substitutes for subsequent grafting fracture healing. These have culminated reconstructive surgery and medical skin to the wound, forming the basis of a this year in the acceptance of a loss conditions. Since the licensure of 2-stage burn treatment strategy. In a manuscript in the important journal, our first skin cell product, Autologous series of animal experiments, the group Clinical Orthopaedics and Related Cultured Keratinocytes for was able to demonstrate that BTM is Research. This technique provides, for Transplantation by the Australian biocompatible and performed equally the first time, an objective method to Therapeutic Goods Administration in well to a commercially available dermal quantify fracture healing and therefore 2006, the laboratory has also taken on substitute, Integra®, in preventing has enormous clinical and research a clinical service role providing cultured wound contraction. Further, it allowed implications. Radiostereometric analysis skin cells to hospitals within Australia re-epithelialisation over the resultant has been used to monitor healing of as well as New Zealand for adult and dermal granulation tissue with complicated fractures which are paediatric burns patients. Applications normal basement membrane formation difficult to manage, including those of of these cells have reportedly improved demonstrating superiority over Integra®. the tibial plateau, the ankle, and the the rate of re-epithelialisation and The laboratory has also successfully distal femur. played a significant role in the survival generated a rudimentary skin-like of critically ill patients. composite by culturing keratinocytes, Drug trials to benefit patients with endothelial cells and fibroblasts renal disease In 2008 the clinical trial to assess the within BTM. The Renal Unit Clinical Trials group potential of freshly isolated, non- currently participates in 20 clinical cultured skin cells in the treatment of This group has also shown that trials and employs five clinical trials a skin depigmentation disease, Vitiligo, BTM can act as a scaffold for the nurses. Their trials cover a broad concluded. It was found that application guided formation of a cultured range of nephrological diseases and of non-cultured skin cells did not microvasculature, which may have treatments. In 2008 the unit expedite re-epithelialisation of partial application in the generation of a collaborated in a wide variety of thickness wounds. However, re- ‘pre-vascularised’ skin substitute and multinational trials including how to pigmentation in areas affected by other tissued engineered organs, to determine the effect of a lipid lowering vitiligo was observed; although the ensure more rapid establishment of therapy on survival and cardiovascular achievement, quality and subsequent blood supply to the grafted tissue events in patients with renal failure; duration of pigmentation was preventing tissue death. This work how to determine the effect of the unpredictable and disappointing. was published in Journal of Burn calcium mimetic agent Cinacalcet on A paper describing these findings has Care and Research. outcomes of patients on maintenance been accepted for publication by the dialysis; how to determine the effect Journal of Burn Care and Research. The major focus on the laboratory in of a vasopressin receptor antagonist These results have mandated the the coming year will be on the (Tolvaptan) on progression of disease removal of non-cultured epidermal cells generation of a composite skin in patients with autosomal polycystic from the burn surgical protocols at the substitute using an optimised version kidney disease, studies of novel RAH where they were previously of BTM as the scaffold and determining approaches to treating ANCA- intended to expedite donor site and its ability to engraft and heal full- meshed graft interstice epithelialisation. thickness wounds.

28 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL of South Australia’s medical research

Identifying health services that don’t Finally their work in China on the However, between 2004 and 2008, require public funding effects of climate change on the results also indicated a significant In 2008, activities undertaken by the communicable disease and on HIV/AIDS reduction in levels of confidence Public Health section at the RAH has resulted in a number of regarding the helpfulness of both focussed on two main areas: health publications. Most of this work has now therapists and pharmacological care and population health. The group been completed and activities in this treatments, perhaps a reflection of continued to provide high level area are likely to reduce during 2009 as recent negative media representation evidence to policy makers across the research on health care increases. of the South Australian mental health Australia about the best medicines system. There were also some changes and health services to introduce and Survey on mental health literacy in SA in literacy across demographic groups, reimburse. During the past year they The Discipline of Psychiatry at with important improvements in those have been instrumental in providing the RAH are undertaking research living in rural areas and those between the evidence to underpin a change in evaluating mental health within the 21 and 35 years of age. This paper has the national breast cancer screening South Australian population, drawing been submitted to the Australian and program from film to digital on data collected through the South New Zealand Journal of Psychiatry. mammography. They have also been Australian Health Omnibus Survey. successful in attracting grant funding, Data collection covers three points in Current research is investigating in particular to investigate health time: 1998, 2004, and 2008. Specifically, population levels of depression, services (including diagnostic tests), the data incorporates information about assessed by the Mood Module of the that no longer need to be supported depression, bipolar disorder, suicidal Primary Care Evaluation of Mental by public funding. This project is being ideation, quality of life, co-morbidities Disorders instrument (PRIME-MD), undertaken in collaboration with policy (such as diabetes and asthma), which delineates DSM-IV mood makers across Australia and in the service use, mental health literacy, and disorders. Participants were assessed UK. They have presented some of this medication use. for symptoms of major depression, work at international conferences and partial remission of major depression, increasingly are seen as international Research has included an evaluation minor depression, dysthymia, double leaders in this area.The group of the concept of mental health literacy. depression, sub-syndromal depression, undertake a range of other research A method and algorithm for calculating and bipolar disorder. Comparisons will activities in health care including levels of mental health literacy was be made between measures taken in investigating tests directly marketed devised allowing comparisons of 1998, 2004, and 2008 as well as across to consumers, models of breast cancer levels of literacy to be made across demographic groups, groups with care applicable to developing countries, populations and time. The method also varying levels of mental health literacy, methods of assessing the social value offers increased capacity for statistical and groups according to Body Mass of diagnostic tests and the role of application. Tracking mental health Index. telehealth. Much of this work will literacy within populations is important continue in 2009 and beyond. as it has been shown to be related These projects contribute significantly to individual help-seeking as well as to the understanding we have of Their work in population health is also provision of support for those with a prevalence and severity of mental broad ranging. They have completed mental disorder. This paper has been illness in the South Australian studies on the way in which health accepted for publication in the Journal population, as well as evaluating the surveillance systems could be changed of Evaluation in Clinical Practice. relationship with co-morbid conditions. to monitor the impact of policies on By informing stakeholders, the findings health inequalities. This work has been A second research project was contribute to improving the mental accepted in a high impact international developed to assess changes in health of South Australians. public health journal American population levels of understanding Journal of Public Health. In 2008, of depression as well as consumer work they completed investigating confidence in both mental health the impact of British nuclear testing therapists and treatment options in South Australia was also published. between 1998 and 2008. Although The work has been instrumental in overall levels of depression-related compensation decisions for servicemen mental health literacy did not improve exposed to this testing. significantly between 2004 and 2008, some discreet, yet important changes were uncovered. Specifically, significantly more people in 2008 correctly classified depression than in previous years.

29 Annual Report 2008 Hanson Institute Research Themes

THIS CENTRE brings together neurosurgeons, neurologists, neuropathologists and neuroscientists in collaboration to optimise the diagnosis and management of patients with head and spinal injury and enhance research into retinal neurodegenerative disease, Parkinson’s and Alzheimer’s. Neurological Diseases

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best OPHTHALMIC RESEARCH LABORATORY of South Australia’s medical research

L>R Andreas Ebunter, Glyn Chidlow, Robert Casson, Bruce Heidemann, Mathew Holman, Tuyet Tran, Mark Daymon, John Wood

Reducing substance P: a key to managing Elevated intracranial pressure reduces Bleeding is common following traumatic patients with traumatic brain injury blood flow to the brain and, if severe, brain injury and the group now Traumatic brain injury is the leading may cause substantial deformation have two models of haemorrhage cause of death and disability in people of the brain and movement within the (intracerebral and subarachnoid) under 45 years of age in Australia, cranial cavity. Intracranial pressure successfully established in the affecting the young and adults in the is one of the best predictors of clinical laboratory. These are being used to most productive years of their lives and outcome after traumatic brain injury investigate the role of substance P predominantly caused by motor vehicle and, as such, has been a target for in haemorrhage, and particularly accidents. Moreover, for every fatality, interventional drug therapies. in the brain oedema formation that there are many survivors with severe accompanies brain haemorrhage. brain damage and many more with The Neuropathology Research Their preliminary results suggest moderate or mild head injury. Although Laboratory now have preliminary that inhibiting substance P reduces traumatic brain injury is a problem of evidence that agents that reduce pericontusional oedema formation and major medical and socioeconomic substance P activity after traumatic may therefore be useful in managing significance, its pathogenesis is brain injury could be useful in reducing the secondary injury process following incompletely understood and it is often vascular leakage and subsequent haemorrhage. difficult to reconstruct the complex cerebral oedema formation, thus events leading to primary (occurring preventing dangerous increases in Spinal cord injury at the moment of head impact) and intracranial pressure. Substance P is an Spinal cord injury occurs at a rate secondary (evolving over time) lesions abundant neurotransmitter in the brain of 300-400 new cases per year in of varying severity and regional and one of its functions is to produce Australia and ongoing costs for long- distribution that constitute traumatic increased vascular permeability, which term care of these affected individuals brain injury. Secondly, although a host results in cerebral oedema. Reducing is approximately $500 million per year. of neuroprotective agents have been activity of substance P after traumatic Despite the enormity of the problem, no studied, the few that have shown brain injury has been shown to treatment currently exists to attenuate promise under experimental conditions markedly reduce cerebral oedema and the neuronal cell death that may occur have failed to provide consistent and improve motor and cognitive outcomes. after the traumatic event. This may be significant improvements in human The laboratory is currently conducting due, in part, to the causes of cell death clinical trials. However, testing the further studies to confirm these in the different forms of spinal cord efficacy of new drugs in the laboratory promising initial findings and, if injury not having been fully elucidated. will continue to be an essential substantiated, these could lead to Studies this year have focussed on precursor to their use in humans and clinical trials in human traumatic brain characterising the cell death following the number of patients requiring these injury patients. different forms of spinal cord injury in drugs unfortunately does not abate. the hope that understanding the injury process will better allow development One of the major clinical problems after of a neuroprotective therapy. traumatic brain injury is increased permeability of small blood vessels, which leads to leakage of excessive volumes of fluid into the brain (cerebral oedema) and raised intracranial Intracranial pressure is one of the best pressure. predictors of clinical outcome after traumatic brain injury and, as such, has been a target for interventional drug therapies

31 Annual Report 2008 Hanson Institute Proudly bringing together the best NEUROLOGICAL DISEASES of South Australia’s medical research

Investigations on neurodegenerative Advances in research on retinal and optic Further research will determine disease nerve injury whether this substance actually Parkinson’s disease is a degenerative The Ophthalmic Research protects nerve cells from injury. condition that causes cell death of a Laboratories (ORL) is the laboratory This research was published in the subset of brain cells containing the research arm of the South Australian leading laboratory-based ophthalmic chemical neurotransmitter dopamine. Institute of Ophthalmology. This Centre journal, Investigative Ophthalmology Oxidative stress has been implicated in of excellence in eye care in Australia and Visual Science. the degeneration of dopamine cells in runs an international outreach program Parkinson’s disease. In 2008, the group in Myanmar, once known as Burma. The group have collaborated with investigated the role of trophic growth This year members of the ORL an Adelaide-based ophthalmic laser factors (GDNF) on the dopamine cells published several articles including company and have been investigating before and after toxic oxidative stress one in the high impact journal the effects of a new form of laser on the was administered with the selective Ophthalmology, reporting on the retina. This laser may replace existing dopamine neurotoxins, rotenone and prevalence of myopia (refractive error lasers used for the treatment of MPTP. Here they used their newly in the eyes) of rural people of Myanmar diabetic retinopathy and other retinal developed cell culture system to keep according to age, gender and education diseases. They are currently running the dopamine secreting cells alive in level. The report found that myopia was a randomised prospective study conditions similar to that of the brain. more prevalent in older subjects and comparing the safety and efficacy of Various methods were employed to higher than that found in other Asian the new laser with the old laser. count the cells, study their function and regions indicating a greater level of analyse apoptotic (programmed) cell visual impairment in these people. Glaucoma is a disease which causes death signals both histologically and degeneration of the optic nerve, but biochemically. They found that GDNF The ORL has expanded exponentially remarkably little is known about this provides protection for dopamine since its inception in 2005. The group degeneration. The ORL have used a rat secreting neurons when given to cells have developed a range of in vitro laser model of glaucoma to investigate after the neurotoxin but not when given and in vivo models and have produced the pathological changes in the optic before. This work has been submitted a number of publications in leading nerves and found that microglial cells for publication. ophthalmic journals. Their success has that act as the main form of active been acknowledged by the NHMRC immune defence in the brain, are active The laboratory has also been with consecutive Project Grants in 2007 early time points. investigating the role of substance and 2008. The group are currently P (SP) in cell death in Parkinson’s conducting a number of basic science They also continued research into the disease. SP is a neuropeptide that projects aimed at providing a better enhancement of energy supply to the functions as a neurotransmitter and as understanding of retinal cell biology retina and optic nerve. The hypothesis a neuromodulator, where it alters the and pathology of retinal and optic is that energy supplementation to the excitability of pain responsive neurons. nerve diseases. In 2008 the laboratory retina could be a useful treatment It is also found in the brain and spinal developed a number of culture modality for many blinding diseases. cord and is associated with some and animal models of glaucoma Here they have shown that creatine, inflammatory processes. It appears to and ischaemic retinal disease. a high energy non-toxic supplement, be involved in the dopaminergic cell They collaborated with colleagues at is protective. A novel finding was that death in early Parkinson’s disease. Melbourne University to show that a elevated blood glucose levels protect Using in vivo models, the laboratory widely used model of glaucoma may the retina against reduced blood flow. has shown that agents that prevent have certain drawbacks and this has led This is a remarkable finding which the action of substance P can attenuate to the laboratory developing a much contradicts current dogma but may the progression of the disease as improved model of adult rat retinal have clinical benefits. demonstrated by improvements in ganglion cells (specialised cells which motor outcome. die in glaucoma).

Frontotemporal dementias The group continue to investigate the The laboratory is continuing its role of the substance called osteopontin investigations into clinicopathologic in the injured retina. Osteopontin is a profile of non-Alzheimer’s dementias. cytokine released by many cells in the They have applied several novel body and has been found to be involved immunocytochemical markers including in a range of physiological and TDP-43, ubiquitin and tau, to enable pathological processes. This year they them to recognise different disease found that osteopontin was upregulated types in this group of dementias. in the retina after an ischaemic injury and that it was produced by central nervous system immune cells.

32 Annual Report 2008 Hanson Institute Research Themes

THE CENTRE for Biomedical Research brings together research groups working in various fields which include studies on infectious diseases, including Hepatitis B, Hepatitis C, AIDS and dengue; developing new typing procedures for viral and bacterial agents affecting public health; understanding the pathogenesis of vascular disease that leads to renal failure; and studies to determine the mechanism(s) underpinning birth defects and cognitive anomalies caused by infections or alcohol exposure in pregnancy. Biomedical

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best BIOMEDICAL of South Australia’s medical research

Dietary zinc protects the foetus against The group has shown that when mice Whatever the answer, it is now exposure to alcohol and infections during are prenatally exposed to infection or becoming clear that successful control pregnancy alcohol, metallothionein attracts zinc of a chronic HBV infection by antiviral The risk of fetal brain damage by from the mother’s blood into her liver drug therapy will significantly reduce consuming low-to-moderate levels of reducing the amount of zinc available the normally high risk of progression alcohol during pregnancy is the subject to the foetus. Zinc is essential for many to cirrhosis and liver cancer. of much current debate. It has been processes and even a transient Unfortunately, the current generation of suggested that even low levels of deficiency can hinder the development antiviral drugs has a very low success alcohol intake may result in adverse of the fetal brain. In 2008 the group rate, leading to virus clearance in no neurodevelopmental and behavioural published in Behavioural Brain more than 20% of HBV carriers. outcomes. However it is also argued Research showing that when mice that interpretation of the current were given alcohol in early pregnancy, Therefore, the major goal of the literature is difficult since it is neither equivalent to weeks 3-8 in humans, Hepatitis B Virus Research large nor conclusive and there is they produced pups that had significant Laboratory is to design improved a significant heterogeneity in memory impairments in adulthood. therapies for chronic HBV infections methodology between epidemiological A most important finding was that the to prevent progression to cirrhosis and studies. A ‘no safe level’ policy has been poor cognition in offspring was liver cancer. This goal is being pursued adopted by the NHMRC in the ‘Draft prevented by providing the mother through 3 lines of research with Australian Alcohol Guidelines for Low- with dietary zinc supplementation international collaborators that are risk Drinking’ mainly based upon the throughout pregnancy. It is believed the being performed in the woodchuck premise that as the relative risk has not extra zinc in the diet buffers the fetal hepatitis virus and duck hepatitis been determined across a range of zinc supply by saturating the alcohol B virus models and using HBV infected drinking levels and there is evidence or infection-mediated metallothionein human and chimpanzee liver. of genetic and age variability to alcohol, response in the mother’s liver. it is only reasonable on a population Resolution of acute HBV infections basis to take a conservative approach. The laboratory is now investigating The group are determining how the However this is not necessarily a whether a mother, with an underlying immune system resolves acute HBV popular view and more evidence is low-grade infection, can cause infections and eliminates the stable required to convince the public, and neurodevelopmental damage to her nuclear form of HBV DNA, covalently even some in the medical profession, foetus by consuming low-to-moderate closed circular DNA (cccDNA). that a low-level intake can pose a levels of alcohol. This work is supported Their previous data has indicated that significant risk. Missing from this debate for the next three years by NHMRC extensive hepatocyte death with is the consideration that individuals funding. activation of Kupffer cells (scavenger may have other predisposing factors cells that remove cellular debris and that can heighten the overall risk from What causes Hepatitis B infections to pathogens) occurs during the recovery alcohol. become chronic and progress to liver phase of acute woodchuck hepatitis cancer? virus infections. These findings imply The Drugs and Metals Research Despite the availability of a protective that therapies for chronic HBV infection Group have been investigating the hepatitis B virus (HBV) vaccine, the also require extensive hepatocyte role that metallothionein plays in fetal number of cases of HBV infection turnover to help eliminate cccDNA. damage from a range of toxins. continues to increase with 350 million Recent studies from the laboratory Metallothionein is a zinc-binding protein HBV carriers worldwide. Chronic HBV have determined that cccDNA is able that is markedly increased in the infection is linked to high rates of liver to survive cell division and is the major mother’s liver as part of her immune disease, cirrhosis and primary liver form of residual duck hepatitis B virus response to alcohol or to infection in cancer. The reason why some HBV DNA present in the liver following the early pregnancy. The first trimester is infections are successfully resolved resolution of acute infection making this most pertinent because it encompasses while others remain chronic is not a key target during the resolution of a period when the mother is often known. acute infection. unaware of her pregnancy and therefore is a time when the foetus is most vulnerable to damage from alcohol. In this regard, surveys have indicated that as many as 60% of pregnancies are unplanned and that the consumption of alcoholic beverages is not curtailed until pregnancy is diagnosed. The number of cases of HBV infection continues to increase with 350 million HBV carriers worldwide

34 Annual Report 2008 Hanson Institute Proudly bringing together the best HEPATITIS C VIRUS RESEARCH LABORATORY of South Australia’s medical research

L>R Satiya Wati, Gorjana Radisic, Eddie Tse, Clarissa Tan, Michael Beard, Erin McCartney, Nicholas Eyre, Evelyn Yip, Karla Helbig

Development of vaccines for infection and have recently found Another family of ISGs being treatment of chronic infections similar levels of proliferation in the liver investigated are the CXCR3 chemokine The laboratory is also developing novel of chimpanzees and humans with family that are responsible for attracting vaccines against HBV infection chronic HBV infection. inflammatory cells to sites of infection. including naked DNA, whole-cell DNA, Here they have shown that the CXCR3 and recombinant fowlpoxvirus vaccines, Disease progression of major concern chemokines are a significant player in and testing them for their ability to in Hepatitis C infection HCV related inflammation of the liver. protect against and to provide therapy In the majority of cases, Hepatitis C Furthermore they have found that for chronic duck hepatitis B virus virus (HCV) infection progresses to a HCV can specifically increase infections. Their ultimate goal is to chronic infection of the liver and over expression of these chemokines and define a protocol for combination a period of two to three decades can thus contribute to increased liver antiviral and vaccination treatments progress to liver failure and in some disease. Understanding chemokine that either eliminates chronic HBV cases, liver cancer. However, the networks in hepatitis C will aid in our infection, or achieves a level of control mechanisms responsible for this disease understanding of liver disease with the of infection that minimises ongoing progression are not well understood. ultimate aim in development of novel disease. This might occur by antiviral The Hepatitis C Virus Research therapeutics to control inflammation. targeting of the cccDNA in infected Laboratory focuses on a number This work was a collaborative effort hepatocytes to reduce virus loads to of projects investigating disease between Hanson Institute and virtually undetectable levels. Part of mechanisms in chronic hepatitis C University of Adelaide investigators this work was published in the journals and HCV biology. and was published in the top ranking of Virology and Journal of Virology Journal of Virology. in 2008. HCV infection of the liver cells results in the activation of thousands of genes Consumption of alcohol increases Pre-malignant changes in the some which are responsible for liver disease progression in chronic hepatitis chronically infected liver disease and others in clearing the virus C although the mechanisms are unclear. Studies are also underway to from infected cells. One family of genes Using a laboratory based model system understand how the infected that are significantly switched on are the laboratory found that alcohol hepatocyte population changes during the Interferon Stimulated Gene (ISG) metabolism increases HCV replication chronic HBV infection and how these family. The laboratory is particularly and furthermore attenuates treatment changes lead to the development of interested in one ISG called viperin that of chronic hepatitis C with interferon liver cancer. The group hypothesise they have shown has anti-HCV activity (IFN). They have now determined the that during chronic HBV infection the and localises in infected cells to lipid molecular basis for this attenuation as body’s immune response kills infected droplets which are a site of HCV being an alcohol induced block in IFN hepatocytes and further provides a replication. Further the group have signalling pathways. This work was a growth advantage to hepatocytes that shown that viperin associates with collaborative effort between Hanson can no longer be infected with HBV. two HCV proteins essential for Institute and University of Sydney This leads to the clonal proliferation replication by which means it is thought investigators and was published in the of HBV-negative hepatocytes that over it disrupts HCV replication complexes. high ranking Journal of Infectious time become the major cell population The laboratory has also demonstrated Diseases. in the liver. The group have evidence that viperin is antiviral against Dengue for extensive clonal proliferation of virus, however the mechanism seems to hepatocytes in woodchucks with be different to that of HCV. Mutational chronic woodchuck hepatitis virus analysis of viperin action will identify a novel antiviral mechanism that may lead to new therapeutic strategies.

35 Annual Report 2008 Hanson Institute MICROBIOLOGY RESEARCH AND Proudly bringing together the best of South Australia’s medical research DEVELOPMENT LABORATORY

L>R Chun Chun Young, Michael Heuzenroeder, Ian Ross

HCV entry into the liver cell initially A number of serovars of Salmonella It had been reported in the literature requires the interaction of the virus (a serovar can loosely be regarded as a that some of the loci used in MLVA with the cell membrane and involves variety) do not possess typing methods typing (Multi locus VNTR Analysis – a receptor, SR-BI (a high-density of sufficient discriminatory power to be a widely accepted method for typing lipoprotein [HDL] receptor) and the of use in tracing. bacteria) could mutate or change proteins CD81 (a tetraspanin), and during an outbreak scenario. claudin-1 (a tight-junction protein). In 2008, they have developed several The laboratory therefore investigated Studies of SR-BI function in mice have new typing methodologies and the stability of the MLVA loci by passing indicated that its interaction with a compared them with conventional Salmonella bacteria through the cytoplasmic adaptor molecule, PDZK1, methods. The serovars investigated intestinal tract of chickens. is necessary for its stability and included Salmonella Typhimurium They hypothesised that under activity at the plasma membrane of and Salmonella Infantis and resulted in laboratory conditions these loci are hepatocytes. The group are currently two journal publications. A comparison stable since there are no strong investigating the importance of this of typing methods for Salmonella selective pressures on the bacterium, interaction to the involvement of SR-BI Enteritidis and Salmonella Virchow however in the harsh environment of in HCV entry. Beyond mapping domains was also undertaken, the former being the chicken gut, selective pressure of each protein involved in this a pathogen of worldwide concern. results in minor changes to the loci or interaction, they have shown that In collaboration with The Australian instability. This is the first such study RNAi-dependent knockdown of PDZK1 Salmonella Reference Laboratory the of its type where it was found that expression results in inhibition of HCV laboratory has continued to assist The instability in some of these loci occurs entry. It is hoped that this work will Communicable Disease Control Branch after passage through the chicken reveal a receptor-protein interaction in Adelaide with investigation of gut, whereas no changes occurred that can be used as a therapeutic target selected Salmonella outbreaks as in the laboratory grown strains. to prevent HCV entry. required. An invitation to the National The conditions of the chicken gut are Face to Face Meeting organised by seen to more closely reflect a ‘real Salmonella typing to trace the source Ozfoodnet and SA Health reflects the world’ scenario, such as would occur of food poisoning outbreaks growing acceptance of these during an outbreak. The changes or The Microbiology Research and methodologies. instability of the loci can have important Development Laboratory is involved implications in the accuracy of results in the development of improved typing One of the most important aspects in used for organism tracing and it is methodologies for the bacterium, any typing system is the stability of the important to have some measure of Salmonella that is an important food- parameters used in the typing process. stability of loci used in typing. borne pathogen. Accurate and rapid typing is required by public health and food safety authorities to trace the source of the contaminating bacteria when outbreaks of food poisoning occur. The molecular methods they have developed are less subjective and faster than existing methods. Accurate and rapid typing is required by public health and food safety authorities to trace the source of the contaminating bacteria when outbreaks of food poisoning occur

36 Annual Report 2008 Hanson Institute Proudly bringing together the best BIOMEDICAL of South Australia’s medical research

A manuscript is in preparation The prevalence in the symptomatic These assays will be used describing this phenomenon and the children was 17% compared with 8% in collaboratively by a number of other group have applied for funding from the volunteers. Statistical analysis of laboratories in both developed and The Rural Industries Research and these results shows an association with developing countries to assess Development Corporation to extend disease. They are currently extending the global distribution and prevalence these studies in a new project that the screening to patients of other age of Adelavirus. Answers to the third would begin in 2009. groups and other years. question will improve our understanding of the replication of In conjunction with Professor Mary Will an antigen capture immuno- Adelavirus, the first step in developing Barton at The University of South assay detect Adelavirus in faecal a vaccine or a therapeutic treatment Australia the laboratory continues to samples? in the future. The results have been investigate the use of bacteriophages Antigen capture immuno-assays are the submitted for publication. (bacterial viruses) to control the most common commercially available multiplication of bacteria that are diagnostic assay for screening for the A link between infection and inflammatory common in food animals presence of enteric viruses. To develop disease of blood vessels (Campylobacter & Escherichia coli) a prototype assay, the laboratory has The main focus of the Renal Research that can cause food poisoning. made artificial empty virus particles Laboratory is to determine the Bacteriophages which are highly host from which they can make specific pathogenesis of systemic necrotising specific can infect and kill these antibody. Both the artificial particles vasculitis, an inflammatory condition bacteria and are seen as an alternative and the antibody can be incorporated of blood vessels, such as Wegener’s to the use of antibiotics as a control in immunoassays to either detect Granulomatosis and Microscopic measure. Reduction of pathogenic Adelavirus in faecal samples or specific Polyangiitis. These are life-threatening bacteria in food products is desirable antibody in patient’s serum, indicative medical conditions with features of to reduce the likelihood of disease of an immune response to Adelavirus myalgia, arthralgia, inflammation of the in humans. infection. Both the artificial virus respiratory tract and very often, the particles and specific antibody have development of acute renal failure due A newly identified virus causing childhood been manufactured and a preliminary to glomerulonephritis. Its aetiology is gastroenteritis in SA immunoassay developed. Current work not known, however there is a strong Acute gastroenteritis is a serious is focused on purifying the reagents association between this disease and disease affecting all age groups further to improve the specificity of the development of antibodies to worldwide. However a causal agent the assay. neutrophil cytoplasmic antigens cannot be found for every infected (ANCA) in patients. An association individual. Previous research by the Can a cell culture system be between infection and disease has long Viral Epidemiological Laboratory developed in which Adelavirus will been suspected and hence the group attempted to address this problem replicate, allowing them to study are particularly interested in the role by searching for the presence of novel the infection cycle? of Toll-like receptor stimulation in the agents in faecal samples from Being able to replicate the virus in pathogenesis of this disease. Toll-like symptomatic children for which current cell lines growing in the laboratory receptors are a group of proteins on the testing was negative. These samples is the first step in understanding the surface of immune cells that recognise came from a collaborative study with replication mechanism and how it bacteria and viruses and then activate the Women’s and Children’s Hospital may be inhibited or blocked. the body’s immune cell response. into the prevalence of known causal Growing enteric viruses in cell cultures agents and lead to the discovery of is rarely successful but already they In 2008, the research concentrated a novel parvovirus, which they called have evidence of moderate replication on the biological interaction between Adelavirus. in two gut tissue-derived cell lines. neutrophils and B cells, in particular, Further, they have linked fluorescent on a molecule released by neutrophils The work this year has addressed stain to the antibody described above at the time of infection. As bacterial three related questions: and used it to demonstrate the DNA is known to induce B cell How important is Adelavirus as presence of VP2, the major capsid proliferation and antibody production a causal agent in acute protein, in the cultured cells. This work via Toll-like receptor stimulation, the gastroenteritis? is continuing, focusing on improving group explored the possibility that To answer this question the group have the efficiency of replication. immunostimulatory DNA sequences screened samples from 186 infected such as unmethylated CpG children and 186 volunteers of the same Answers to the first two questions will oligodeoxynucleotide, as found age in hospital for a reason unrelated result in improved diagnostic testing for in bacterial and viral DNA, may to acute gastroenteritis. what appears to be an important cause play a role in stimulating circulating of acute gastroenteritis. autoreactive B cells to produce ANCA in patients with vasculitis.

37 Annual Report 2008 Hanson Institute Proudly bringing together the best BIOMEDICAL of South Australia’s medical research

The laboratory found that this molecule This temperature-arrested state In collaboration with Dr David Shaw leads to rapid sensing of bacterial DNA appears stable and does not allow and Lyndal Daly at the Infectious and CpG oligodeoxynucleotides by B fusion-mediated HIV infection to Diseases Unit, RAH, the group have cells. In the work published in BMC progress further resulting in pre- continued with an on-going study to Immunology, they argue that this fusion intermediates with changed monitor drug resistance and the levels mechanism may act as a bridge between conformation that exposes potential of HIV DNA inside the circulating cells innate and adaptive immunity by antigenic epitopes. The laboratory has of patients that are receiving a new allowing rapid detection of bacterial now developed enrichment methods kind of antiretroviral therapy called DNA at the time of infection thus and fixation conditions to capture Integrase inhibitors. This study will potentially providing the link between these intermediates that carry broadly continue in 2009 and will yield infection and ANCA associated neutralising B cell epitopes against important novel results on the vasculitis. the virus and use them as ‘designer effectiveness and mechanisms of action antigens’ to produce bNABs against of these new agents when used in HIV/AIDS, dengue and influenza are HIV in animals. This basic research a real world clinical setting. viral infections that are global issues, project will contribute new and valuable being a major threat to both Western knowledge towards novel, alternative Cellular responses in dengue virus and third world cultures. The Virus HIV vaccine design. infected cells Research Laboratory has continued The hunt for a vaccine against Dengue its important research work on these Laboratory techniques to enhance clinical virus (DV) continues unabated in three viruses. management of HIV infection Australia as more than 300 cases have Clinical management of HIV infection is been reported in Far North Queensland Novel method to produce neutralising ever changing as new drug therapies and experts are concerned it will antibodies against HIV become available that are very effective eventually migrate further south. Unfortunately, traditional HIV antigen in reducing the circulating level of DV is a mosquito borne infection that preparations and viral antigen virus down to levels below the can cause either mild infection or expression regimes have not produced sensitivity of traditional laboratory severe and fatal haemorrhagic disease. broadly neutralising antibodies (bNABs) tests. Additionally, while antiretroviral The severity of disease is believed to be that can meet the global health drugs are very effective, the virus determined by the way the recipient’s challenge for a vaccine against HIV. always wins and manages to develop cell changes when it is infected One of the first steps in HIV infection is drug resistance, thus requiring the with virus and this is the subject of the attachment of the virus to the host continual development of new drug investigation by the Virus Research cell via a cellular receptor (CD4) where targets and methods for monitoring the Laboratory. They previously have viral entry is mediated by co-receptor changing patterns of drug resistance. reported that DV infected cells don’t (CCR5/CXCR4) engagement and fusion In 2008, the Virus Research Laboratory react normally to a stimuli from the of the viral and cellular membranes. continued to develop techniques to cytokine, TNFα, which is released During this attachment and entry monitor low levels of drug resistance by the host in response to infection. process, conserved and broadly to one of the most commonly observed In 2008, they found that this altered neutralising antigenic determinants resistance sites (K103N) which results TNFα response caused the cells to die. against HIV are transiently exposed in loss of effectiveness of a major class This occurred specifically in infected at normal body temperature (37°C). of HIV antiretroviral agents (termed cells that were starting to produce virus Using a cell-to-cell HIV infection model, NNRTI’s). The study identified low as one of the viruses own proteins (DV the Virus Research Laboratory has level drug resistance in a further 15% capsid) was found to be responsible shown that the viral fusion process can of patients above that seen by for this effect. be arrested at various temperatures traditional tests. below 25°C leaving viral pre-fusion intermediates essentially frozen in time.

The hunt for a vaccine against Dengue virus (DV) continues unabated in Australia as more than 300 cases have been reported in Far North Queensland and experts are concerned it will eventually migrate further south

38 Annual Report 2008 Hanson Institute Proudly bringing together the best BIOMEDICAL of South Australia’s medical research

Work continues to fully understand this They have shown that a single process which may have important intranasal administration of γ- implications for how the body gets rid A/PR8[H1N1] protects mice against of the virus during a DV infection in lethal H5N1 and H3N2 infection. humans. A second area of investigation The underlying mechanism for the is to determine the role of a cellular detected cross-protective immunity protein (GRP78) in DV infection. is currently under investigation. In collaboration with Dr Michael Beard They believe that intranasal γ-Flu and Professor James Paton the group represents a unique approach for a have shown that by reducing the levels cross-protective vaccine against both of GRP78, the virus can infect and seasonal as well as possible future replicate in cells but cannot continue pandemic influenza A virus infections. the infection cycle as they cannot make the proteins necessary to exit the cell. By comparison with HCV (from the same Flaviviridae family as DV) and HIV (from a different virus family) they believe that this is a specific requirement for DV and the Flaviviridae group of viruses, and potentially could be exploited as a means of reducing release of infectious virus.

Gamma-ray irradiation used to prepare vaccines against lethal strains of influenza Current influenza A vaccines rely exclusively on antibody responses and require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. A collaborator, Professor Arno Müllbacher at the Australian National University was the first to demonstrate that gamma (γ), rays can be used to inactivate influenza virus to prepare a vaccine (γ-Flu) which induces cross- reactive cytotoxic T cell responses. The reduced impact of γ-irradiation on the antigenic structure of viral particles is thought to improve the magnitude and/or quality of humoral immunity elicited in vaccine recipients over that obtained by using current vaccines. The Virus Research Laboratory have continued their collaboration with ANU and the Australian Animal Health Laboratory in Geelong investigating the use of γ-Flu as a vaccine candidate to induce heterotypic and cross-protective immunity against influenza A virus including avian H5N1.

39 Annual Report 2008 Hanson Institute

THE HANSON INSTITUTE Core Facilities are a collection of campus-wide, laboratories for developing and providing state-of-the-art facilities and resources conducive to facilitating outstanding research. They ensure our researchers have access to highly- specialised research services and costly instrumentation avoiding duplication expense and effort. These facilities are available on a fee-for-service basis to the entire research campus and to the wider research community in SA. The Adelaide Microarray Centre and the Adelaide Proteomics Centre are collaborative efforts with the University of Adelaide. Core Facilities

Proudly bringing together the best of South Australia’s medical research Hanson Institute Proudly bringing together the best ADELAIDE MICROARRAY CENTRE of South Australia’s medical research

L>R Mark Van der Hoek, Rosealie Kenyon

Adelaide Microarray Centre • Provided over 200 Affymetrix array Biotech Industry. The Centre also The Adelaide Microarray Centre was services. provided services in protein separation, established in 2000 to provide the local • Completed over 1200 sample quantification and identification and research community convenient access analyses on the Agilent Bioanalyzer. edman sequencing as a fee for service and is actively involved in grant to affordable microarray technology. • Purchase of a Biorad RT-PCR applications which include proteomics During the last eight years, in excess machine and introduction of a experiments. of 7000 arrays have been manufactured microRNA RT-PCR service (Taqman). by the facility targeting a variety of • Staff attended Partek analysis genomes including human, mouse and The Centre has seven PhD students training workshops and the AMATA zebrafish. Expertise in fabricating working on a variety of projects on 2008 array conference in Dunedin, arrays, designing and conducting proteins ranging from investigations on NZ. microarray experiments and analysing phosphorylation, modification, protein- microarray data constitute the protein interaction, profiling proteins In 2009 the Centre will work with SA comprehensive service the facility in plasma to identify novel biomarkers Pathology to implement array based provides to researchers. The centre of disease, development of new diagnostic services. works closely with a number of proteomics methods for further use in the Centre and commenced in 2008, researchers who have a strong interest Adelaide Proteomics Centre in microRNA profiling and has much a new study to identify auto antibodies In 2008, the second year of full expertise in this field. in blood as a marker for early stage operation, the Adelaide Proteomics detection of ovarian cancer. All-in-all Centre continued the development of In 2007 the Centre installed an the Centre has had a successful year in a number of technologies and projects Affymetrix TG microarray system performing services and attracting more – both clinical and basic. The Centre including dual fluidics stations and the students to commit to research projects performed more than 120 projects using latest four colour Genechip scanner as in the field of Proteomics. Proteomics technology and mass well as an Agilent Bioanalyzer. This spectrometry for researchers and expansion of services resulted in the The Detmold Family Imaging Facility biotech companies in Adelaide, centre relocating from the University of The Detmold Family Imaging Facility Australia and overseas. The MALDI Adelaide to larger premises within SA is a state-of-the-art facility for flow TOF/TOF mass spectrometer is used Pathology. Adoption of the Affymetrix cytometry and cell/tissue imaging routinely for the identification of array platform gives local researchers available to all researchers on campus proteins from protein containing gel access to a much wider range of assays and to the wider scientific community plugs to gel electrophoretic separations and applications including Exon of South Australia. of protein mixtures in a high expression profiling, ChIP-on-Chip throughput and high sensitive fashion. assays and SNP/cGH analysis. This Facility offers two analytical Ion Trap mass spectrometer online- flow cytometers and two high speed coupled to a nano-flow HPLC using a Centre Highlights for 2008 include: cell sorters. Flow cytometry allows new Chip technology is employed for • Centre (re)opening by Professor researchers to analyse mixed the identification of post-translational Brendon Kearney in June in new populations of cells, chromosomes, modifications in proteins and more premises. yeast and other small ‘particles’, complex samples. Methods for protein • Manufactured and sold over 1000 determining the composition of that separation (2D gel electrophoresis) spotted microarrays and associated mixture using fluorescently tagged and protein quantification (DIGE services to many different research probes (typically fluorescently tagged technology) are routinely offered as a institutions throughout Australia. antibodies or specialist reagents) service for researchers of the Hanson specific for cell surface or intracellular • Continued to receive contracts to Institute and the University of Adelaide target molecules. print custom arrays (eg coral). as well as for other academics and the

41 Annual Report 2008 Hanson Institute Proudly bringing together the best CORE FACILITIES of South Australia’s medical research

The presence or absence of these As part of the system, a new image In addition to the cryogenic storage molecules defines sub populations server was installed and commissioned, vessels, the Facility provides two of cells, giving clues to researchers allowing remote access to these high ‘controlled rate freezers’. These units regarding these populations and their resolution images through web-based are cooled by controlled injection of role in disease and normal states. software. This software allows scanning liquid nitrogen into the chamber and Flow cytometry allows rapid and highly and zooming of the enormous image freeze specimens in a rigorously sensitive processing, and profiles these files via the Web, and users can controlled manner, maximising the mixed cell populations ‘cell by cell’ to annotate the images with observations quality of the material. These freezers provide population statistics in minutes which can be shared amongst were replaced with new models during for tens of thousands of cells. colleagues from different locations. 2008.

Flow cytometric cell sorters have an The Detmold Family Imaging Facility This cryogenic facility provides medium added capability. Cells of a known employs specialist scientific staff to to long term storage solutions to a ‘profile’ can be identified and purified operate the instrumentation and variety of users. A major use of the from the mixture of cells. Researchers provide support for users of the facility. facility is the storage of critical clinical can purify the various sub-populations Crucial to providing a specialist material used for haemopoietic stem they identify and rigorously test service is providing the opportunity for cell transplantation. At present, these purified cells for their function. staff to keep abreast of the latest approximately 2500 bags of peripheral The sorters within the Facility are methodologies and technology in the blood stem cell ‘blood bags’ are in capable of performing sorts at rates area. In 2008, Dr Sarvestani was invited storage for use in transplantation for up to 25,000 events per second. to conduct advanced microscopy patients, with an additional 4000 In 2008, the Facility performed 70,000 lectures and a full one week workshop specimens for quality testing. Skin stem flow cytometry analyses and 570 cell at Kuwait University, attended the cells are also being stored for treatment sorting sessions. Advanced Bio-Imaging Workshop held of burns patients. The Facility now in Hawkesbury Campus, UWS, and stores approximately 800 additional The Facility also operates two confocal provided lectures and workshops for transplant blood bag specimens for microscopes that have different students of the University of South The Queen Elizabeth Hospital, with capabilities to meet a broad range of Australia and University of Adelaide. additional 1700 quality testing applications. Confocal microscopy Ms Katherine Pilkington travelled to specimens in storage for TQEH. allows ‘optical sectioning’ to visualise Perth for the Australasian Flow specific molecules within cells and Cytometry Group 31st Annual Meeting. In addition to providing cryogenic tissues. The Facility has recently storage for clinical use, the facility also upgraded the Nikon C1 confocal The Central Liquid Nitrogen Facility has a very large and growing tissue microscope with new high numerical The Central Liquid Nitrogen Facility bank. This resource is invaluable to aperture lenses, a transmission detector is an integral part of the Tissue Bank basic and clinical researchers alike, as well as new image analysis software at SA Pathology and commenced permitting retrospective studies of for 3-D rendering and quantification. operations in November 2006 to provide many disease states. Currently, over This upgrade, in conjunction with the a centralised cryogenic facility service 160,000 specimens are in storage, and existing Bio-Rad Radiance 2001 for the SA Pathology/Hanson Institute this category continues to grow rapidly confocal microscope, has substantially campus. The new facilities were with the ongoing centralisation of increased the capabilities of the Facility, constructed and many state-of-the-art cryogenic storage within the Hanson which now has options to image features were incorporated, including Institute and SA Pathology. A significant specimens in a complete spectral range a number of sophisticated safety amount of research material (cell lines) from UV to Far Red laser illumination as mechanisms to avert the hazards and pathology specimens (biopsies and well as transmission light reflection. associated with large volumes of liquid a variety of isolates) are also stored This equipment was used in numerous nitrogen. within the facility, with stocks currently research projects in 2008 and over 1100 standing at approx 60,000 specimens. hours of acquisition time was recorded. The inventory within the Facility is managed by a custom designed web- The material stored in this facility is A new addition to the Facility was based database, allowing the facility to largely irreplaceable, and of immense the microscope slide scanner called operate as a ‘library service’, where value to current clinical practice and the Nanozoomer. This state of the art users order samples for retrieval from furthering scientific and clinical technology was acquired through the facility and can deposit new endeavour for future generations. a collaboration of researchers and specimens. The Facility has installed pathologists from the University of additional vessels and now has 25 Adelaide, the Hanson Institute and state-of-the-art cryogenic vessels that SA Pathology. operate in ‘vapour phase’ for cryogenic preservation (liquid nitrogen has a temperature of –196ºC, and the vapour phase storage compartment is at least –170ºC). 42 Annual Report 2008 Hanson Institute Proudly bringing together the best CORE FACILITIES of South Australia’s medical research

Veterinary Services Division give clients (those with new In order to address public concern The Veterinary Services Division drugs/devices) the necessary quality about potential risks to human (VSD) of SA Pathology exists to assurance when proceeding to clinical health, the World Health Organisation support research in the Hanson and trials. Device testing (implants, drug has given a high priority to wider scientific community. delivery systems) has emerged as a determining whether exposure to The extensive experience of VSD niche market utilising our expertise mobile phones injures the immature staff in animal experimentation and in in large animal research. brain. SA Pathology has studied the the management of research projects brains of fetal mice exposed for the has enabled them to make major Institutional collaborations were whole of pregnancy, and during the contribution to the SA Pathology, conducted in two areas of diagnostic neonatal period, and no deleterious University of Adelaide and Women’s pathology: changes have been found to date. and Children’s Hospital Animal Ethics • Preclinical toxicology program for This research has been facilitated Committees (AEC) and to provide Biotechnology companies in Australia by funding from the Australian consultancy to researchers establishing and overseas Government since SA Pathology is a partner in the Australian Centre for projects involving animals. • Laboratory animal health diagnostic Radiofrequency Bioeffects Research, The secretary (Ms Carol Hewitt) of the service (MVMS) – a large number of an NH&MRC Centre of Research AEC is situated at Gilles Plains and university and hospital laboratory Excellence. consequently, they are the front-line of animal facilities Australia-wide and the committee, dealing with issues on a overseas daily basis. These contributions include, • Peripheral nerve disorders One of the most frequent diseases but are not limited to, problem solving, Large Animal Imaging affecting peripheral nerves is loss of advice on animal models, statistical A Large Animal Research and the myelin sheath that encloses the advice on experimental design, Imaging Facility (LARIF) was axon or nerve fibre, resulting in assistance with surgical techniques, established at the Veterinary Services, impaired conduction of nerve organising laboratory testing, Gilles Plains field station and is run by impulses, muscle weakness and even contributing to education days and VSD staff. The facility was opened on paralysis. However, the mechanisms promoting the use of standard 24th November 2008 by the Minister by which the myelin sheath is procedures. for Science and Information Economy, degraded (demyelination) and the Hon Paul Caica, MP. It is now replenished (remyelination) are Preclinical services providing tools for applying the latest incompletely understood. We have Contract research has emerged as a developments in magnetic resonance used a riboflavin (vitamin B2) major activity in the Veterinary Services (MRI) and other imaging modalities for deficiency model of Division with considerable potential. research into animal models of human demyelination/remyelination to study It has evolved from their research and disease. The LARIF incorporates a new these processes in the hope that diagnostic capabilities. As this activity building, a 1.5 T MR scanner and new therapeutic intervention strategies has grown it has enabled them to animal holding facilities and is funded can be developed to halt myelin loss recruit high quality staff and to through a National Collaborative and promote its restitution. purchase specialised equipment, Research Infrastructure Scheme further adding to their capabilities. ($3.5M, involving both Federal, State, • Bioavailability of Heavy Metals Clients have come, in the main, from SA Pathology, and University(s) funds). the Biotechnology sector. The identified Collaborative studies continued with The Centre for Environmental Risk gap in the Australian market is the Research Activities Assessment and Remediation at provision of preclinical safety testing In 2008, staff of the VSD conducted the UniSA, Mawson Lakes campus, to the highest recognised international research activities in four main areas: guidelines (GLP; Good Laboratory to examine the bioavailability of • Effect of mobile telephones on Practice). Australia is attractive for a heavy metals in food and soil using the developing brain number of reasons, including a stable a pig model. Other bioavailability Many millions of individuals are now political environment, excellent models using mice to examine the regularly exposed to mobile phone facilities and competitive cost bioavailability of residual chemicals microwaves in utero and postnatally structures. Safety testing (also known and heavy metals in the soils are as these devices are increasingly as Toxicity testing) is a well defined to be pursued. The heavy metal lead integrated into daily life. In addition service in the sense that any company (Pb) remains an environmental to fetal exposure, the human brain wanting to advance a drug/device into hazard for intellectual development continues to grow for a substantial clinical trials, must do this type of in children. period after birth and mobile phones testing. GLP compliant safety studies are held close to the head. However, very few studies have assessed the vulnerability of developing brains to these radiofrequency fields.

43 Annual Report 2008 Hanson Institute Proudly bringing together the best CORE FACILITIES of South Australia’s medical research

• Effects of Alcohol on Fetal Monoclonal Antibodies SA (MAbSA) Development In 2008, MAbSA operations were Effects of alcohol and other relocated to the SA Pathology campus teratogens on the developing foetus. at Gilles Plains and this, together with Studies have focused on neurological a revision of staffing, has resulted in development and have included increased efficiency and reduced costs. cognitive testing, treatment The outlook is very positive with two strategies with Zn, and gene array large-volume commercial projects methodologies. In 2008, funding starting in February 2009 and these was obtained from the NH&MRC, will test MAbSA’s capacity to provide Channel 7 Research Foundation the service and meet the demands over and the Alcohol and Health Research the next two years. Foundation to continue studies in this area. During the year, MAbSA was engaged in 13 new hybridoma projects, mostly Research collaborations were also from interstate, and 23 antibody conducted with other institutions production and purification projects. including In addition, more projects asked for the • RMIT, Monash and Swinburne fragmentation, conjugation and labelling Universities and Telstra – of antibodies. ‘Neurological effects of mobile telephone exposure’ (NH&MRC Requests for quotation have decreased Centre of Research Excellence, the with facilities now competing on-line Australian Centre for Radiofrequency in Victoria, Queensland and Western Bioeffects Research) Australia. However, MAbSA services are considered to be competitive in price • Royal Adelaide Hospital and quality of service. MAbSA has had Cardiovascular Research Unit – ‘Stem solid reviews from their past clients cell repair of myocardial infarction’ and this has resulted in gaining more • Department of Medical Sciences, commercial work particularly in large University of Adelaide – ‘Mechanisms volume services from biotechnology of, and development of drug companies. One such contract was from intervention strategies for, traumatic a State where a competitor is based. brain injury’ MAbSA has expanded services in • University of South Australia, Centre response to special requests from for Environmental Reclamation and clients. They now offer an antibody Remediation, Mawson Lakes. pair screening test to identify partner monoclonal antibodies suitable for sandwich ELISA assays, recovery of contaminated cells and labelling of antibodies with special tags. They are also investigating long-term storage of hybridoma and other cell types in the central liquid nitrogen facility.

44 Annual Report 2008 Hanson Institute Proudly bringing together the best MEMBERSHIP TO 31ST DECEMBER 2008 of South Australia’s medical research

*New Members in 2008 MARSHALL, Villis R AC, MBBS, MD, FRACS, Professor Member MAYRHOFER, Graham BLACKSHAW, L Ashley BM, BCh, DPhil, MA, Associate Professor BSc(Hons), PhD, Professor *MELO, Junia BLUMBERGS, Peter C MD, PhD, FRCPath, Professor MBBS, FRACP, FRCPA, Professor MOORE, Robert BROWN, Michael P MAppSci, PhD, Associate Professor MBBS(Hons), FRACP, FRCPA, Associate Professor MORRIS, Howard BURRELL, Christopher BSc(Hons), PhD, FAACB, ARCPA, Professor AO, BSc(Med)(Hons), MBBS, PhD, FRCPA, FRCPath(UK), Professor PITSON, Stuart CALLEN, David F BAppSc, PhD BSc(Hons), PhD, Professor REYNOLDS, Paul N CHAPMAN, Ian MBBS, PhD, FRACP, Associate Professor MBBS, FRACP, PhD, Associate Professor SANDERS, Prash CHATTERTON, Barry MBBS(Hons), PhD, FRACP, Professor MBBS, FRACP, DDU SCICCHITANO, Raffaele CLELAND, Leslie G MBBS, PhD, FRACP, Associate Professor MBBS, MD, FRACP, Clinical Professor SCOTT, Hamish D’ANDREA, Richard BSc(Hons), PhD, Professor BSc(Hons), PhD, Associate Professor *SWEENEY, Chris DENT, John MBBS, Professor MB BChir, FRACP, FRCP, PhD, Professor TEMLETT, James FAZZALARI, Nick L MB BCh, DA, FCP, MMed(Neuro), PhD, FRCP, FCNeurol, Associate BAppSc, BSc(Hons), DipEd, PhD, Professor Professor FINDLAY, David THOMPSON, Philip BSc(Hons), MSc, PhD, Professor MBBS, ECFMG, FRACP, PhD, Professor FINNIE, John TILLEY, Wayne BSc(Hons), BVSc, MSc, PhD BSc(Hons), PhD. Professor FRASER, Robert JL TO, L Bik MBBS, FRACP, PhD MBBS, MD, MRCPath(UK), FRCPA, FRACP, Professor GOLDNEY, Robert TORPY, David MBBS, FRANZCP, MD, FRCPsych, Professor MBBS, FRACP, PhD, Associate Professor GOODALL, Gregory J VINK, Robert BSc(Hons), PhD, Associate Professor BSc(Hons), PhD, Professor *GRONTHOS, Stan WHITE, Jason M MSc, PhD, Associate Professor BSc(Hons), PhD, Professor GUTHRIDGE, Mark WITTERT, Gary BSc(Hons), PhD MBBCh, FRACP, MD, Professor HILLER, Janet WORTHLEY, Stephen DipSocStudies, BA(Psych), MPH, PhD, Professor MBBS, PhD, FRACP, Professor HOLTMANN, Gerald *ZANNETTINO, Andrew MD, Professor BSc(Hons), PhD, Associate Professor HOROWITZ, Michael MBBS, PhD, FRACP, Professor Associate Members HUGHES, Timothy P ATKINS, Gerald MBBS, MD, FRACP, FRCPA, Clinical Professor BSc(Hons), PhD JAMES, Michael J BAGLEY, Christopher BAgSc(Hons), PhD, Professor BSc(Hons), PhD KEEFE, Dorothy BEARD, Michael R MBBS, FRACP, MD, Professor BSc(Hons), PhD *KHEW-GOODALL, Yeesim BONDER, Claudine BSc(Hons), PhD BSc(Hons), PhD KUCHEL, Tim BUTLER, Lisa BVSc, MVS, DVA BSc(Hons), PhD KUMAR, Sharad CASSON, Robert MSc, PhD, Professor MBBS(Hons), DPhil, FRANZCO, Associate Professor LOPEZ, Angel F COVENTRY, Brendon J MBBS, PhD, MRCPath(UK), FRCPA, Professor MBBS, PhD, FRACS, Associate Professor

45 Annual Report 2008 Hanson Institute Proudly bringing together the best MEMBERSHIP TO 31ST DECEMBER 2008 of South Australia’s medical research

EVDOKIOU, Andreas External Members BSc, MSc, PhD Associate Professor COATES, Toby FAULL, Randall MBBS, PhD MBBS, FRACP, PhD D’ANDREA, Richard FEINLE-BISSET, Christine BSc(Hons), PhD, Associate Professor MMedSc, PhD, Associate Professor DREW, Paul GREENWOOD, John BSc, PhD AM, BSc(Hons), MBChB, MD, FRCS(Eng), FRCS(Plast), FRACS GALLETLY, Cherrie HARVEY, Natasha MBChB, DPM, FRANZCP, PhD, Professor BSc(Hons), PhD KOBLAR, Simon HAYBALL, John D MBBS, PhD, FRACP, Associate Professor BSc, DIC, PhD LYONS, A Bruce HODGE, Sandy BSc(Hons), PhD DipAppSci, MSc, PhD, Associate Professor McCOLL, Shaun HOFFMANN, Peter PhD, Professor MChem, PhD McKINNON, Ross HORSFALL, David J BPharm, BSc(Hons), PhD, Professor BSc(Hons), PhD, Associate Professor MAY, Brian JILBERT, Allison BSc(Hons), PhD, Associate Professor BSc(Hons), PhD ROBERTSON, Sarah JONES, Karen BSc(Hons), PhD, Associate Professor DipAppSci, PhD, Associate Professor WILLIAMS, Desmond O’LOUGHLIN, Peter BPharm, MSc, PhD, FRACI, FAICD BSc(Hons), PhD WINEFIELD, Helen PEH, Chen Au BA(Hons), PhD, FAPS, Professor MBBS, FRACP, PhD RATCLIFF, Rodney M Honorary Members BSc(Hons), PhD KEARNEY, Brendon RAYNER, Chris AM, MBBS, FRACP, FRACMA, Professor MBBS, PhD, FRACP, Associate Professor NORDIN, BE Christopher RUSZKIEWICZ, Andrew AO, MD, PhD, DSc(London & Adelaide), FRACP, Visiting Professor MD, FRCPA Emeritus Members WOODCOCK, Joanna BSc(Hons), PhD GOLLAN, John L MBBS, MD, MRACP, MRCP, PhD, Professor Affiliate Members JUTTNER, Christopher A BEILBY, Justin BMedSc, MBBS, FRACP MBBS, MD, MPH, FRACGP, DA, DRCOG, Professor MARMION, Barrie P BIGNOLD, Leon AO, Emeritus Professor MBBS, MD, FRACP, FRCPA VERNON-ROBERTS, Barrie CLIFTON, Peter M AO, MD, PhD, FRCPath, FRCPA, FAOrthA(Hon), Emeritus Professor MBBS, BMedSci, MRCP, FRACP, PhD, Professor COYLE, Peter BSc(Hons), MAppSc, PhD, MAACB, Associate Professor HARDINGHAM, Jennifer BAppSci, PhD HEUZENROEDER, Michael BSc(Hons), PhD, FASM HOLMES, Mark MBBS, MD, FRACP, Associate Professor HOWIE, Don MBBS, FRACS, PhD, Professor LEWIS, Ian MBBS, PhD, FRACP, FRCPA PENG, Li PhD ROFE, Allan BAgSci(Hons), PhD

46 Annual Report 2008 Hanson Institute Proudly bringing together the best MEMBERSHIP TO 31ST DECEMBER 2008 of South Australia’s medical research

Criteria for Membership Member Applicable to basic laboratory or clinical investigators, with MBBS or PhD, source of salary, significant body of publications in quality journals, international recognition, established external funding record and autonomous line of research, with an effective and viable independent laboratory program. Associate Member Applicable to basic laboratory and clinical investigators, with MBBS or PhD, significant body of publications in quality journals, potential for attracting ongoing independent funding and capability of establishing an autonomous line of research. Affiliate Member For campus or external staff who are committed to supporting research with MBBS or PhD, whose field(s) of interest, as judged by the Hanson Institute Membership and Management Committees, is in the long term strategic interest of the Hanson Institute and with tangible support for research. External Member Specifically directed to eminent colleagues and collaborators with MD or PhD or equivalent, source of own salary, significant body of publications in quality journals, international recognition, established external funding record, established autonomous line of research and a field of interest that is complementary to those of the Hanson Institute and judged by the Hanson Institute Membership Committee to be in the long term strategic interest of the Hanson Institute. Honorary Member For eminent individuals who have not previously been a Member/Associate Member of the Hanson Institute, but have contributed substantially to ideals and development of the Institute. Emeritus Member Specifically for previous Members of the Hanson Institute.

47 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

9 Anderson PH, Hendrix I, Sawyer RK, Zarrinkalam R, Manavis J, Hanson Institute Publications Sarvestani GT, May BK, Morris HA. Co-expression of CYP27B1 enzyme with the 1.5kb CYP27B1 promoter-luciferase transgene in the 08 79 / 491 mouse. Molecular & Cellular Endocrinology 285:1-9, 2008. 10 Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris 07 67 / 429 HA. Vitamin D depletion induces RANKL-mediated osteoclastogenesis 06 61 / 424 and bone loss in a rodent model. Journal of Bone & Mineral Research 23:1789-1797, 2008. 05 44 / 328 11 Andreazza HJ, Fitzgerald M, Bilusich D, Hoffmann R, Hoffmann P, Eichinger PC, Bowie JH. Characteristic negative ion fragmentations of 04 42 / 320 deprotonated peptides containing post-translational modifications: mono-phosphorylated Ser, Thr and Tyr. A joint experimental and 0 50 100 150 200 250 300 350 400 450 500 theoretical study. Rapid Communications in Mass Spectrometry Number of Publications 22:3305-3312, 2008. Impact factor >=6 / Annual Total 12 Andrews JM, Fraser RJ, Heddle R, Hebbard G, Checklin H. Is esophageal dysphagia in the extreme elderly (>/=80 years) different to Publications in peer-reviewed journals are one of the major dysphagia younger adults? A clinical motility service audit. Diseases outcomes of scientific research. Publication in respected journals of the Esophagus 21:656-659, 2008. is a key link in the chain of scientific investigation enabling new 13 Aprile G, Ramoni M, Keefe D, Sonis S. Application of distance ideas to be communicated, challenged and tested. matrices to define associations between acute toxicities in colorectal The quality of scientific journals varies and is measured by cancer patients receiving chemotherapy. Cancer 112:284-292, 2008. their impact factor, a calculation that quantifies the impact of 14 Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S. Adult human the science published by that journal. The quality of research dental pulp stem cells differentiate towards functionally active neurons is assessed at an international level by the publication in the under appropriate environmental cues. Stem Cells 26:1787-1795, highest impact factor journals. 2008. This year Hanson Institute researchers published 491 15 Asquith KL, Ramshaw HS, Hansbro PM, Beagley KW, Lopez AF, Foster Manuscripts, 79 of which were published in high impact scientific PS. The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in journals (Impact Factor 6 or greater). the regulation of Th2 immunity and allergic airway inflammation. Journal of Immunology 180:1199-1206, 2008. 1 Aakre KM, Thue G, Subramaniam-Haavik S, Bukve T, Morris H, Müller 16 Astill DS, Jones N, Vivek J, Blumbergs PC. A supratentorial cyst Part M, Lovrencic MV, Plum I, Kallion K, Aab A, Kutt M, Gillery P, 1. Pathology 40:520-523, 2008. Schneider N, Horvath AR, Onody R, Oosterhuis W, Ricos C, Perich C, 17 Athanasiov PA, Casson R, Sullivan T, Newland HS, Shein WK, Muecke Nordin G, Sandberg S. Postanalytical external quality assessment of J, Selva D, Aung T. Cataract in Rural Myanmar: Prevalence and risk urine albumin in primary health care: an international survey. Clinical factors from the Meiktila Eye Study. British Journal of Ophthalmology Chemistry 54:1630-1636, 2008. 92:1169-1174, 2008. 2 Abdul-Rahman AM, Casson RJ, Newland HS, Mueke JS, McGovern 18 Athanasiov PA, Casson RJ, Newland HS, Shein WK, Muecke JS, Selva ST, Aung TH, Selva DN, Aung T. Pseudoexfoliation in a rural Burmese D, Aung T. Cataract surgical coverage and self-reported barriers to population: The Meiktila Eye Study. British Journal of Ophthalmology cataract surgery in a rural Myanmar population. Clinical & 92:1325-1328, 2008. Experimental Ophthalmology 36:521-525, 2008. 3 Abraham LM, Epasinghe NC, Selva D, Casson R. Comparison of the 19 Athanasiov PA, Prabhakaran VC, Selva D. Non-traumatic ICare® rebound tonometer with the Goldmann applanation tonometer enophthalmos: a review. Acta Ophthalmology 86:356-364, 2008. by experienced and inexperienced tonometrists. Eye 22:503-506, 20 Athanasiov PA, Prabhakaran VC, Selva D. Unilateral orbital fibrosis 2008. with blepharoptosis and enophthalmos. Ophthalmic Plastic & 4 Adhikari R, Gunatillake PA, Griffiths I, Tatai L, Wickramaratna M, Reconstructive Surgery 24:156-158, 2008. Houshyar S, Moore T, Mayadunne RT, Field J, McGee M, Carbone T. 21 Atlantis E, Martin SA, Haren MT, Taylor AW, Wittert GA; Florey Biodegradable injectable polyurethanes: synthesis and evaluation for Adelaide Male Aging Study. Lifestyle factors associated with age- orthopaedic applications. Biomaterials 29:3762-3770, 2008. related differences in body composition: the Florey Adelaide Male 5 Alimohammadi M, Björklund P, Hallgren A, Pöntynen N, Szinnai G, Aging Study. American Journal of Clinical Nutrition 88:95-104, 2008. Shikama N, Keller MP, Ekwall O, Kinkel SA, Husebye ES, Gustafsson J, 22 Barr RK, Lynn HE, Moretti PA, Khew-Goodall Y, Pitson SM. Rorsman F, Peltonen L, Betterle C, Perheentupa J, Akerström G, Westin Deactivation of sphingosine kinase 1 by protein phosphatase 2A. G, Scott HS, Holländer GA, Kämpe O. Autoimmune polyendocrine Journal of Biological Chemistry 283:34994-35002, 2008. syndrome type 1 and NALP5, a parathyroid autoantigen. New England Journal of Medicine 358:1018-1028, 2008. 23 Bashey A, Pérez WS, Zhang MJ, Anderson KC, Ballen K, Berenson JR, To LB, Fonseca R, Freytes CO, Gale RP, Gibson J, Giralt SA, Kyle RA, 6 Al-Mawali A, Gillis D, Hissaria P, Lewis I. Incidence, sensitivity, and Lazarus HM, Maharaj D, McCarthy PL, Milone GA, Nimer S, Pavlovsky specificity of leukemia-associated phenotypes in acute myeloid S, Reece DE, Schiller G, Vesole DH, Hari P; Plasma Cell Disorders leukemia using specific five-color multiparameter flow cytometry. Working Committee. Comparison of twin and autologous transplants American Journal of Clinical Pathology 129:934-945, 2008. for multiple myeloma. Biology of Blood & Marrow Transplantation 7 Alsharifi M, Lobigs M, Bettadapura J, Koskinen A, Mullbacher A. 14:1118-1124, 2008. Restricted Semliki Forest virus replication in perforin and Fas-ligand 24 Bastian I, L Krause V. Tuberculosis: the dis-ease that didn’t dis-appear. double-deficient mice. Journal of General Virology 89:1942-1944, Medical Journal of Australia 188:131-132, 2008. 2008. 25 Batterham M, Cavanagh R, Jenkins A, Tapsell L, Plasqui G, Clifton P. 8 Anderson PH, Atkins GJ. The skeleton as an intracrine organ for High-protein meals may benefit fat oxidation and energy expenditure in vitamin D metabolism. Molecular Aspects of Medicine 29:397-406, individuals with higher body fat. Nutrition & Dietetics 65:246-252, 2008. 2008.

48 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

26 Baumert M, Smith J, Catcheside P, McEvoy RD, Abbott D, Sanders P, 45 Brinkworth GD, Wycherley TP, Noakes M, Clifton PM. Reductions in Nalivaiko E. Variability of QT interval duration in obstructive sleep blood pressure following energy restriction for weight loss do not apnea: an indicator of disease severity. Sleep 31:959-966, 2008. rebound after re-establishment of energy balance in overweight and 27 Beard MR, Helbig KJ. Control of HCV replication: When size does not obese subjects. Clinical & Experimental Hypertension 30:385-396, matter. Hepatology 47:1092-1094, 2008. 2008. 28 Beetstra S, Suthers G, Dhillon V, Salisbury C, Turner J, Altree M, 46 Brooks AG, Wilson L, Kuklik P, Stiles MK, John B, Shashidhar , McKinnon R, Fenech M. Methionine-dependence phenotype in the de Dimitri H, Lau DH, Roberts-Thomson RL, Wong CX, Young GD, novo pathway in BRCA1 and BRCA2 mutation carriers with and Sanders P. Image integration using NavX fusion: Initial experience and without breast cancer. Cancer Epidemiology Biomarkers & Prevention validation. Heart Rhythm 5:526-535, 2008. 17:2565-2571, 2008. 47 Butcher CM, Hahn U, To LB, Gecz J, Wilkins EJ, Scott HS, Bardy PG, 29 Beilby J, Williams S, Levy ML. Systems for the management of D’Andrea RJ. Two novel JAK2 exon 12 mutations in JAK2V617F- primary care respiratory disease throughout the world. Primary Care negative polycythaemia vera patients. Leukemia 22:870-873, 2008. Respiratory Journal 17:5-6, 2008. 48 Byles JE, Carroll M; Mars and Venus Writing Team: Cumming B, 30 Bi P, Tully PJ, Boss K, Hiller JE. Sharps injury and body fluid exposure Flicker L, Wittert G, Dobson A, Banks E, Mishra G, Russell C, Wainer among health care workers in an Australian tertiary hospital. Asia J. Mars and Venus: does gender matter in ageing? Medical Journal of Pacific Journal of Public Health 20:139-147, 2008. Australia 188:271-273, 2008. 31 Bignold LP, Coghlan BL, Jersmann HP. Virchow’s “cellular pathology” 49 Cakouros D, Mills K, Denton D, Paterson A, Daish T, Kumar S. 150 years later. Seminars in Diagnostic Pathology 25:140-146, 2008. dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes. Journal of Cell Biology 182:481- 32 Bignold LP. The “aneuploidy-modified mutator-phenotype” theory of 495, 2008. malignant tumors. Cellular Oncology 30:459, 2008. 50 Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, 33 Blackshaw LA. New insights in the neural regulation of the lower Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S, Yang B. Nedd4 oesophageal sphincter. European Review for Medical & controls animal growth by regulating IGF-1 signaling. Science Pharmacological Sciences 12:Suppl 1:33-39, 2008. Signaling 1:ra5, 2008. 34 Blake S, Hughes TP, Mayrhofer G, Lyons AB. The Src/ABL kinase 51 Carr JM, Coolen C, Davis AJ, Burrell CJ, Li P. Human inhibitor dasatinib (BMS-354825) inhibits function of normal human immunodeficiency virus 1 (HIV-1) virion infectivity factor (Vif) is part T-lymphocytes in vitro. Clinical Immunology 127:330-339, 2008. of reverse transcription complexes and acts as an accessory factor for 35 Blake SJ, Lyons AB, Fraser CK, Hayball JD, Hughes TP. Dasatinib reverse transcription. Virology 372:147-156, 2008. suppresses in vitro natural killer cell cytotoxicity. Blood 111:4415- 52 Casson RJ, Abraham LM, Newland HS, Muecke J, Sullivan T, Selva D, 4416, 2008. Aung T. Corneal thickness and intraocular pressure in a 36 Blumbergs PC, Reilly PL, Vink R: Trauma. In: Greenfields’ nonglaucomatous Burmese population: The Meiktila Eye Study. Neuropathology, 8th edition, Chapter 11, pp733-832, 2008. Archives of Ophthalmology 126:981-985, 2008. 37 Bonhoure E, Lauret A, Barnes DJ, Martin C, Malavaud B, Kohama T, 53 Casson RJ. Anterior chamber depth and primary angle-closure Melo JV, Cuvillier O. Sphingosine kinase-1 is a downstream regulator glaucoma: an evolutionary perspective. Clinical & Experimental of imatinib-induced apoptosis in chronic myeloid leukemia cells. Ophthalmology 36:70-77, 2008. Leukemia 22:971-979, 2008. 54 Centenera MM, Harris JM, Tilley WD, Butler LM. The contribution of 38 Booth TM, Marmion WJ, Cullimore AM and Finnie JW. Oesophageal different androgen receptor domains to receptor dimerization and obstruction in an aged pony associated with squamous cell carcinoma. signaling. Molecular Endocrinology 22:2373-2382, 2008. Equine Veterinary Education 20:627-631, 2008 55 Chaikomin R, Wu KL, Doran S, Meyer JH, Jones KL, Feinle-Bisset C, 39 Bowen J, Noakes M, Clifton P. Role of protein and carbohydrate Horowitz M, Rayner CK. Effects of mid-jejunal compared to duodenal sources on acute appetite responses in lean and overweight men. glucose infusion on peptide hormone release and appetite in healthy Nutrition & Dietetics 65:S3:71-S78, 2008. men. Regulatory Peptides 150:38-42, 2008. 40 Bowen JM. Prevention and treatment of regimen-related mucosal 56 Chan WO, Madge S, Dodd TJ, Higgs B, Davis G. Multiple cranial toxicity. Recent Patents on Anti-cancer Drug Discovery 3:68-75, 2008. nerve palsies as a result of perineural invasion by squamous cell 41 Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon carcinoma. British Journal of Hospital Medicine (London) MF, Goodall GJ. A double-negative feedback loop between ZEB1-SIP1 69:476-477, 2008. and the microRNA-200 family regulates epithelial-mesenchymal 57 Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, transition. Cancer Research 68:7846-7854, 2008. Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR. Osteal tissue 42 Branford S, Fletcher L, Cross NC, Muller MC, Hochhaus A, Kim DW, macrophages are intercalated throughout human and mouse bone Radich JP, Saglio G, Pane F, Kamel-Reid S, Wang YL, Press RD, Lynch lining tissues and regulate osteoblast function in vitro and in vivo. K, Rudzki Z, Goldman JM, Hughes T. Desirable performance Immunology 181:1232-1244, 2008. characteristics for BCR-ABL measurement on an international reporting 58 Chapman IM. Obesity in old age. Frontiers in Hormone Research scale to allow consistent interpretation of individual patient response 36:97-106, 2008. and comparison of response rates between clinical trials. Blood 59 Chapman MJ, Fraser RJ, Bryant LK, Vozzo R, Nguyen NQ, Tam W, 112:3330-3338, 2008. Zacharakis B, Davidson G, Butler R, Horowitz M. Gastric emptying and 43 Brennan IM, Little TJ, Feltrin KL, Smout AJ, Wishart J, Horowitz M, the organization of antro-duodenal pressures in the critically ill. Feinle-Bisset C. Dose-dependent effects of cholecystokinin-8 on Neurogastroenterology & Motility 20:27-35, 2008. antropyloroduodenal motility, gastrointestinal hormones, appetite and 60 Chassany O, Holtmann G, Malagelada J, Gebauer U, Doerfler H, energy intake in healthy men. American Journal of Physiology. Devault K. Systematic Review: A systematic review of health-related Endocrinology & Metabolism 295:E1487-1494, 2008. quality of life (HRQOL) questionnaires in Gastroesophageal Reflux 44 Brierley SM, Page AJ, Hughes PA, Adam B, Liebregts T, Cooper NJ, Disease (GERD). Alimentary Pharmacology and Therapeutics 27:1053- Holtmann G, Liedtke W, Blackshaw LA. Selective role for TRPV4 ion 1070, 2008. channels in visceral sensory pathways. Gastroenterology 134:2059- 61 Chehade MJ, Bachorski A. Development of the Australian core 2069, 2008. competencies in musculoskeletal basic and clinical science project - phase 1. Medical Journal of Australia 189:162-165, 2008. 49 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

62 Chehade MJ. Journal Scan: Highlights of Australian orthopaedics. 79 Davey RA, Turner A, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Clinical Orthopaedics & Related Research 466:2017-2022, 2008. Atkins GJ, Anderson PH, Ma C, Glatt V, Maclean HE, Vincent C, 63 Chen RY, Nordin BE, Need AG, Scopacasa F, Wishart J, Morris HA, Bouxsein M, Morris HA, Findlay DM, Zajac JD. The calcitonin receptor Horowitz M. Relationship between calcium absorption and plasma plays a physiological role to protect against hypercalcemia in mice. dehydroepiandrosterone sulphate (DHEAS) in healthy males. Clinical Journal of Bone & Mineral Research 23:1182-1193, 2008. Endocrinology (Oxford) 69:864-869, 2008. 80 Davis AJ, Carr JM, Bagley CJ, Powell J, Warrilow D, Harrich D, Burrell 64 Chidlow G, Wood JP, Manavis J, Osborne NN, Casson RJ. Expression CJ, Li P. Human immunodeficiency virus type-1 reverse transcriptase of osteopontin in the rat retina: effects of excitotoxic and ischemic exists as post-translationally modified forms in virions and cells. injuries. Investigative Ophthalmology & Visual Science 49:762-771, Retrovirology 5:115, 2008. 2008. 81 Deane A, Young R, Chapman M, Fraser R. A clinical audit of the 65 Chin KF, Myers JC, Jamieson GG, Devitt P Symptoms experienced efficacy of tegaserod as a prokinetic agent in the intensive care unit. during 24-h pH monitoring and their relationship to outcome after Critical Care and Resuscitation 10:71, 2008. laparoscopic total fundoplication. Diseases of the Esophagus 21:445- 82 Dent J, Kahrilas PJ, Hatlebakk J, Vakil N, Denison H, Franzén S, 451, 2008. Lundborg P. A randomized, comparative trial of a potassium- 66 Chittleborough CR, Baum F, Taylor AW, Hiller JE. Missing data on competitive acid blocker (AZD0865) and esomeprazole for the retrospective recall of early-life socio-economic position in treatment of patients with nonerosive reflux disease. American Journal surveillance systems: An additional disadvantage? Public Health of Gastroenterology 103:20-26, 2008. 122:1152-1166, 2008. 83 Dent J, Kahrilas PJ, Vakil N, Veldhuyzen van Zanten S, Bytzer P, 67 Chittleborough CR, Taylor AW, Baum FE, Hiller JE. Non-response to a Delaney B, Haruma K, Hatlebakk J, McColl E, Moayyedi P, Stanghellini life course socioeconomic position indicator in surveillance: V, Tack J, Vaezi M. Clinical trial design in adult reflux disease - a comparison of telephone and face-to-face modes. BMC Medical methodological workshop. Alimentary Pharmacology and Therapeutics Research Methodology 8:54, 2008. 28:107-126, 2008. 68 Chur-Hansen A, Winefield H, Beckwith M. Reasons given by elderly 84 Dent J, Sharma P, Tytgat G. Preface. Best Practice & Research. Clinical men and women for not owning a pet, and the implications for clinical Gastroenterology 22:551, 2008. practice and research. Journal of Health Psychology 13:988-995, 85 Dent J. Endoscopic grading of reflux oesophagitis: The past, present 2008. and future. Best Practice & Research. Clinical Gastroenterology 69 Clifton PM, Keogh JB, Noakes M. Long-term effects of a high-protein 22:585-599, 2008. weight-loss diet. American Journal of Clinical Nutrition 87:23-29, 86 Dent J. Pathogenesis of gastro-oesophageal reflux disease and novel 2008. options for its therapy. Neurogastroenterology & Motility 20 Suppl 70 Clifton PM, Mano M, Duchateau GS, van der Knaap HC, Trautwein EA. 1:91-102, 2008. Dose-response effects of different plant sterol sources in fat spreads 87 Denton D, Mills K, Kumar S. Chapter 2 Methods and protocols for on serum lipids and C-reactive protein and on the kinetic behavior of studying cell death in Drosophila. Methods in Enzymology 446C:17- serum plant sterols. European Journal of Clinical Nutrition 62:968- 37, 2008. 977, 2008. 88 Dickson GR, Geddis C, Fazzalari N, Marsh D, Parkinson I. 71 Clifton PM. Dietary treatment for obesity. Nature Clinical Practice Microcomputed tomography imaging in a rat model of delayed Gastroenterology & Hepatology 5:672-681, 2008. union/non-union fracture. Journal of Orthopaedic Research 26:729- 72 Coghlan BLD, Bignold LP. Virchow's Eulogies. Rudolf Virchow in 736, 2008. Tribute to his Fellow Scientists, Chapter XII, Birkhäuser, Basel, 2008. 89 Diener KR, Lousberg EL, Beukema EL, Yu A, Howley PM, Brown MP, 73 Collins JE, Gill TK, Chittleborough CR, Martin AJ, Taylor AW, Hayball JD. Recombinant fowlpox virus elicits transient cytotoxic T cell Winefield H. Mental, emotional, and social problems among school responses due to suboptimal innate recognition and recruitment of T children with asthma. Journal of Asthma 45:489-493, 2008. cell help. Vaccine 26:3566-3573, 2008. 74 Colloca CJ, Keller TS, Moore RJ, Gunzburg R, Harrison DE. Effects of 90 Diener KR, Moldenhauer LM, Lyons AB, Brown MP, Hayball JD. disc degeneration on neurophysiological responses during Human Flt-3 ligand-mobilized dendritic cells require additional dorsoventral mechanical excitation of the ovine lumbar spine. Journal activation to drive effective immune responses. Experimental of Electromyography and Kinesiology 18:829-837, 2008. Hematology 36:51-60, 2008. 75 Cops EJ, Bianco-Miotto T, Moore NL, Clarke CL, Birrell SN, Butler 91 Doorenbosch X, Harding M. Primary treatment of a blood-blister-like LM, Tilley WD. Antiproliferative actions of the synthetic androgen, aneurysm of the internal carotid artery with Guglielmi detachable coil mibolerone, in breast cancer cells are mediated by both androgen and embolisation. Journal of Clinical Neuroscience 15:1276-1279, 2008. progesterone receptors. Journal of Steroid Biochemistry & Molecular 92 Dorstyn L, Kumar S. A biochemical analysis of the activation of the Biology 110:236-243, 2008. Drosophila caspase DRONC. Cell Death & Differentiation 15:461-470, 76 Coventry BJ. Core biopsy in preoperative planning of definitive soft 2008. tissue tumour surgery. ANZ Journal of Surgery 78:945-946, 2008. 93 Douglas RJ, Cadogan M. Cardiac arrhythmia during propofol sedation. 77 Cross NC, Hughes TP, Hochhaus A, Goldman JM. International Emergency Medicine Australasia 20:437-440, 2008. standardisation of quantitative real-time RT-PCR for BCR-ABL. 94 Douglas RJ. Ooh - bet that hurt. Medical Journal of Australia 189:524, Leukemia Research 32:505-506, 2008. 2008. 78 Cukier K, Pilichiewicz AN, Chaikomin R, Brennan IM, Wishart JM, 95 Duncan EM, Casey GJ, Fenech MP, Lerda NV, Casey CR, Rodgers SE, Rayner CK, Jones KL, Horowitz M, Feinle-Bisset C. Effect of small Lee SH, Chunilal S, Robinson K, Lloyd JV. Partial and severe factor XI intestinal glucose load on plasma ghrelin in healthy men. American deficiency in South Australia and the usefulness of factor XI mutation Journal of Physiology. Regulatory, Integrative & Comparative analysis for diagnosis. Pathology 40:401-406, 2008. Physiology 295:R459-462, 2008. 96 Duncan RF, Brown MA, Worthley SG. Increasing Identification of Isolated Left Ventricular Non-Compaction with Cardiovascular Magnetic Resonance: A Mini Case Series Highlighting Variable Clinical Presentation. Heart Lung & Circulation 17:9-13, 2008.

50 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

97 Duncan RF, Brown MA, Worthley SG. Recurrent, multiple cardiac 116 Eyre NS, Cleland LG, Mayrhofer G. FAT/CD36 expression alone is myxoma. Heart Lung & Circulation 17:142-143, 2008. insufficient to enhance cellular uptake of oleate. Biochemical and 98 Dundon BK, Psaltis PJ, Worthley SG. Cardiac magnetic resonance and Biophysical Research Communications 370:404-409, 2008. “augmented” right-to-left intracardiac shunting through a patent 117 Fazzalari NL. Bone remodeling: A review of the bone microenvironment foramen ovale. Journal of Invasive Cardiology 20:196-197, 2008. perspective for fragility fracture (osteoporosis) of the hip. Seminars in 99 Dundon BK, Puri R, Leong DP, Worthley MI. Takotsubo Cell & Developmental Biology 19:467-472, 2008. cardiomyopathy following lightning strike. Emergency Medicine 118 Feltrin KL, Little TJ, Meyer JH, Horowitz M, Rades T, Wishart J, Feinle Journal 25:460-461, 2008. Bisset C. Comparative effects of intraduodenal infusions of lauric and 100 Dundon BK, Worthley MI, Worthley SG. Very late drug-eluting stent oleic acids on antropyloroduodenal motility, plasma cholecystokinin thrombosis. Heart Lung & Circulation 17:144-145, 2008. and peptide YY, appetite, and energy intake in healthy men. American Journal of Clinical Nutrition 87:1181-1187, 2008. 101 Dundon BK, Yeend RA, Worthley SG. Percutaneous closure of a large peri-prosthetic left ventricular pseudoaneurysm in a high-risk surgical 119 Fenech M, Noakes M, Bowen J, Clifton P. Effect of protein intake, candidate. Heart 94:1043, 2008. hyperglycaernia and micronutrients on DNA damage and mitogen responsiveness of peripheral blood lymphocytes. Nutrition & Dietetics 102 Dunn KI, Mohr PB, Wilson CJ, Wittert GA. Beliefs about fast food in 65:S2:S27-S32, 2008. Australia: A qualitative analysis. Appetite 51:331-334, 2008. 120 Feng F, Wang L, Albanese N, Holmes A, Xia P. TWEAK attenuates the 103 Durkin SR, Abhary S, Newland HS, Selva D, Aung T, Casson RJ. The action of insulin in hepatocytes. Endocrinology 149:1505-1513, 2008. prevalence, severity and risk factors for pterygium in central Myanmar: the Meiktila Eye Study. British Journal of Ophthalmology 92:25-29, 121 Ferguson BJ, Alexander C, Rossi SW, Liiv I, Rebane A, Worth CL, 2008. Wong J, Laan M, Peterson P, Jenkinson EJ, Anderson G, Scott HS, Cooke A, Rich T. AIRE's CARD revealed, a new structure for central 104 Durkin SR. Eye health programs within remote Aboriginal communities tolerance provokes transcriptional plasticity. Journal of Biological in Australia: a review of the literature. Australian Health Review Chemistry 283:1723-1731, 2008. 32:664-676, 2008. 122 Findlay DM, Chehade M, Tsangari H, Neale S, Hay S, Hopwood B, 105 Ecroyd H, Koudelka T, Thorn DC, Williams DM, Devlin G, Hoffmann P, Panach S, O’Loughlin P, Fazzalari NL. Circulating RANKL is inversely Carver JA. Dissociation from the oligomeric state is the rate-limiting related to RANKL mRNA levels in bone in osteoarthritic males. step in amyloid fibril formation by kappa -casein. Journal of Arthritis Research & Therapy 10:R2, 2008. Biological Chemistry 283:9012-9022, 2008. 123 Finnie JW, Manavis J and Blumbergs PC. Aquaporin-4 in acute 106 Edwards B, Galletly C, Semmler-Booth T, Dekker G. Antenatal cerebral oedema produced by Clostridium perfringens type D epsilon psychosocial risk factors and depression among women living in toxin. Veterinary Pathology 45:307-309, 2008. socioeconomically disadvantaged suburbs in Adelaide, South Australia. Australia & New Zealand Journal of Psychiatry 42:45-50, 124 Fitter S, Dewar AL, Kostakis P, To LB, Hughes TP, Roberts MM, Lynch 2008. K, Vernon-Roberts B, Zannettino AC. Long term imatinib therapy promotes bone formation in CML patients. Blood 111:2538-2547, 107 Edwards B, Galletly C, Semmler-Booth T, Dekker G. Does antenatal 2008. screening for psychosocial risk factors predict postnatal depression? A follow-up study of 154 women in Adelaide, South Australia. 125 Fleury V, Kleinig TJ, Thompson PD, Ravindran J. Cardio-embolic Australia & New Zealand Journal of Psychiatry 42:51-55, 2008. cerebellar stroke secondary to mitral valve chordae rupture as a delayed complication of a high-voltage electrical injury. Journal of 108 Edwards NA, Caldicott DG, Aitken P, Lee CC, Eliseo T. Terror Australis Clinical Neuroscience 15:210-212, 2008. 2004: preparedness of Australian hospitals for disasters and incidents involving chemical, biological and radiological agents. Critical Care & 126 Flynn G, Alexander D, Harris A, Whitford T, Wong W, Galletly C, Resuscitation 10:136, 2008. Silverstein S, Gordon E, Williams LM. Increased absolute magnitude of gamma synchrony in first-episode psychosis. Schizophrenia 109 Eliott J, Olver I. Choosing between life and death: patient and family Research 105:262-271, 2008. perceptions of the decision not to resuscitate the terminally ill cancer patient. Bioethics 22:179-189, 2008. 127 Fock KM, Talley NJ, Fass R, Goh KL, Katelaris P, Hunt R, Hongo M, Ang TL, Holtmann G, Nandurkar S, Lin SR, Wong BC, Chan FK, Rani 110 Eliott JA, Kealey CP, Olver IN. (Using) complementary and alternative AA, Bak YT, Sollano J, Ho LK, Manatsathit S. Asia-Pacific consensus medicine: the perceptions of palliative patients with cancer. Journal of on the management of gastroesophageal reflux disease: Update. Palliative Medicine 11:58-67, 2008. Journal of Gastroenterology & Hepatology 23:8-22, 2008. 111 Eliott JA, Olver IN. Dying cancer patients talk about euthanasia. Social 128 Foot NJ, Dalton HE, Shearwin-Whyatt LM, Dorstyn L, Tan SS, Yang B, Science & Medicine 67:647-56, 2008. Kumar S. Regulation of the divalent metal ion transporter DMT1 and 112 Elshaug AG, Hiller JE, Moss JR. Exploring policy-makers’ perspectives iron homeostasis by a ubiquitin-dependent mechanism involving on disinvestment from ineffective healthcare practices. International Ndfips and WWP2. Blood 112:4268-4275, 2008. Journal of Technology Assessment in Health Care 24:1-9, 2008. 129 Foster D, Upton R, Christrup L, Popper L. Pharmacokinetics and 113 Elshaug AG, Moss JR, Hiller JE, Maddern GJ. Upper airway surgery pharmacodynamics of intranasal versus intravenous Fentanyl in should not be first line treatment for obstructive sleep apnoea in patients with pain after oral surgery. Annals of Pharmacotherapy adults. British Medical Journal 336:44-45, 2008. 42:1380-1387, 2008. 114 Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, 130 Galletly CA, McFarlane AC, Clark R. Differentiating cortical patterns of Tishler RB, Canty TP, Kudrimoti MK, Vera-Llonch M; Burden of Illness cognitive dysfunction in schizophrenia and posttraumatic stress Head and Neck Writing Committee. Patient-reported measurements of disorder. Psychiatry Research 159:196-206, 2008. oral mucositis in head and neck cancer patients treated with 131 Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: radiotherapy with or without chemotherapy: demonstration of increased negative, as well as positive, regulators of immunity. Nature Reviews. frequency, severity, resistance to palliation, and impact on quality of Immunology 8:478-486, 2008. life. Cancer 113:2704-2713, 2008. 132 Galligan JJ, Blackshaw LA. (Eds) Purinergic signalling in the 115 Eng HS, Bennett G, Tsiopelas E, Lake M, Humphreys I, Chang SH, gastrointestinal tract. In: Purinergic Signalling 4:195-285, 2008. Coates PT, Russ GR. Anti-HLA donor-specific antibodies detected in positive B-cell crossmatches by Luminex ® predict late graft loss. 133 Galluccio ST, Faull RJ, Ghali J. Extreme hyperkalaemia and American Journal of Transplantation 8:2335-2342, 2008. hypernatraemia in a renal-transplant recipient: where two wrongs make a right? Nephrology (Carlton, Vic) 13:448-449, 2008. 51 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

134 Galluccio ST, Rai S, Sharley P. An unexpected ending: brain death 153 Guipponi M, Toh MY, Tan J, Park D, Hanson K, Ballana E, Kwong D, following acute severe asthma. Critical Care and Resuscitation 10:235- Cannon PZ, Wu Q, Gout A, Delorenzi M, Speed TP, Smith RJ, Dahl 238, 2008. HH, Petersen M, Teasdale RD, Estivill X, Park WJ, Scott HS. An 135 Gentilcore D, Hausken T, Meyer JH, Chapman IM, Horowitz M, Jones integrated genetic and functional analysis of the role of type II KL. Effects of intraduodenal glucose, fat, and protein on blood transmembrane serine proteases (TMPRSSs) in hearing loss. Human pressure, heart rate, and splanchnic blood flow in healthy older Mutation 29:130-141, 2008. subjects. American Journal of Clinical Nutrition 87:156-161, 2008. 154 Gun R, Parsons J, Ryan P, Crouch P, Hiller JE. Mortality and cancer 136 Gentilcore D, Meyer JH, Rayner CK, Horowitz M, Jones KL. 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Toxicology, Gad SC, editor, Wiley, Chapter 3, 2008. 157 Gupta A, Muecke JS. Treatment of radiation maculopathy with 139 Giles FJ, DeAngelo DJ, Baccarani M, Deininger M, Guilhot F, Hughes intravitreal injection of bevacizumab (Avastin). Retina 28:964-968, T, Mauro M, Radich J, Ottmann O, Cortes J. Optimizing outcomes for 2008. patients with advanced disease in chronic myelogenous leukemia. 158 Gustafsson JOR, McColl SR, Hoffmann P. Imaging mass spectrometry Seminars in Oncology 35:S1-17; quiz S18-20, 2008. and its methodological application to murine tissue. Journal of 140 Glasson JH, Guthrie LH, Nielsen DJ, Bethell FA. Evaluation of an Proteomics & Bioinformatics 1:458-463, 2008. automated instrument for inoculating and spreading samples onto agar 159 Haag S, Senf W, Häuser W, Tagay S, Grandt D, Heuft G, Gerken G, plates. Journal of Clinical Microbiology 46:1281-1284, 2008. Talley NJ, Holtmann G. Impairment of health related quality of life in 141 Goldney RD, Fisher LJ. Have broad-based community and functional dyspepsia and chronic liver disease: influence of depression professional education programs influenced mental health literacy and and anxiety. Alimentary Pharmacology and Therapeutics 27:561-571, treatment seeking of those with major depression and suicidal 2008 ideation? Suicide & Life Threatening Behaviour 38:129-142, 2008. 160 Hansen G, Hercus TR, McClure BJ, Stomski FC, Dottore M, Powell J, 142 Goldney RD. Do we do what we know works, and if not why not? Ramshaw H, Woodcock JM, Xu Y, Guthridge M, McKinstry WJ, Lopez Australian & New Zealand Journal of Psychiatry 42:907-908, 2008. AF, Parker MW. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134:496-507, 143 Gordon EJ, Gale NW, Harvey NL. Expression of the hyaluronan 2008. receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vessels. 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170 Hissaria P, Cai FZ, Ahern M, Smith M, Gillis D, Roberts-Thomson P. 186 Hotham E, Ali R, White J, Robinson J. Pregnancy-related changes in Wegener's granulomatosis: epidemiological and clinical features in a tobacco, alcohol and cannabis use reported by antenatal patients at South Australian study. Internal Medicine Journal 38:776-780, 2008. two public hospitals in South Australia. Australian & New Zealand 171 Hissaria P, Smith W, Wormald PJ, Taylor J, Vadas M, Gillis D, Kette F. Journal of Obstetrics & Gynaecology 48:248-254, 2008. Short course of systemic corticosteroids in sinonasal polyposis: A 187 Howell CA, Turnbull DA, Beilby JJ, Marshall CA, Briggs N, Newbury double-blind, randomized, placebo-controlled trial with evaluation of WL. Preventing relapse of depression in primary care: a pilot study of outcome measures. Clinical Otolaryngology 33:29, 2008. the “Keeping the blues away” program. Medical Journal of Australia 172 Hiwase D, Hiwase S, Bailey M, Bollard G, Schwarer A. The role of 188:S138-141, 2008. stem cell mobilization regimen on lymphocyte collection yield in 188 Hubert FX, Kinkel SA, Webster KE, Cannon P, Crewther PE, Proeitto AI, patients with multiple myeloma. Cytotherapy 10:507-517, 2008. Wu L, Heath WR, Scott HS. A specific anti-aire antibody reveals aire 173 Hiwase DK, Hiwase S, Bailey M, Bollard G, Schwarer AP. Higher expression is restricted to medullary thymic epithelial cells and not infused lymphocyte dose predicts higher lymphocyte recovery, which expressed in periphery. Journal of Immunology 180:3824-3832, 2008. in turn, predicts superior overall survival following autologous 189 Hughes G. A pot-pourri of news. Emergency Medicine Journal 25:710, hematopoietic stem cell transplantation for multiple myeloma. 2008. Biology of Blood and Marrow Transplantation 14:116-124, 2008. 190 Hughes T. Is drug treatment superior to allografting as first-line 174 Hiwase DK, Saunders V, Hewett D, Frede A, Zrim S, Dang P, Eadie L, therapy in chronic myeloid leukemia? Nature Clinical Practice. To LB, Melo J, Kumar S, Hughes TP, White DL. Dasatinib cellular Oncology 5:14-15, 2008. uptake and efflux in chronic myeloid leukemia cells: therapeutic 191 Hughes TP, Branford S, White DL, Reynolds J, Koelmeyer R, Seymour implications. Clinical Cancer Research 14:3881-3888, 2008. JF, Taylor K, Arthur C, Schwarer A, Morton J, Cooney J, Leahy MF, 175 Ho LH, Read SH, Dorstyn L, Lambrusco L, Kumar S. Caspase-2 is Rowlings P, Catalano J, Hertzberg M, Filshie R, Mills AK, Fay K, required for cell death induced by cytoskeletal disruption. Oncogene Durrant S, Januszewicz H, Joske D, Underhill C, Dunkley S, Lynch K, 27:3393-3404, 2008. Grigg A. Impact of early dose intensity on cytogenetic and molecular 176 Hochhaus A, Baccarani M, Deininger M, Apperley JF, Lipton JH, responses in chronic phase CML patients receiving 600 mg/day of Goldberg SL, Corm S, Shah NP, Cervantes F, Silver RT, Niederwieser imatinib as initial therapy. Blood 112:3965-3973, 2008. D, Stone RM, Dombret H, Larson RA, Roy L, Hughes T, Müller MC, 192 Hui CH, Horvath N, Lewis I, To LB, Szabo F. Outcome of patients with Ezzeddine R, Countouriotis AM, Kantarjian HM. Dasatinib induces myelodysplastic syndromes - experience from a single institution in durable cytogenetic responses in patients with chronic myelogenous South Australia. Internal Medicine Journal 38:824-828, 2008. leukemia in chronic phase with resistance or intolerance to imatinib. 193 Hui CH, Lee HH. Cryoglobulins. Medical Journal of Australia 188:158, Leukemia 22:1200-1206, 2008. 2008. 177 Hodge G, Hodge S, Reynolds PN, Holmes M. Airway infection in 194 Hui CH, Sia H, Mangos H, Horvath N, Lee H, Lewis I, Hughes T, To stable lung transplant patients is associated with decreased LB, Bardy P. Daclizumab has poor efficacy in steroid-refractory severe intracellular T-helper type 1 pro-inflammatory cytokines in acute graft-versus-host disease: a single centre experience with 12 bronchoalveolar lavage T-cell subsets. Transplant Infectious Disease allograft patients. Bone Marrow Transplantation 41:409-410, 2008. 10:99-105, 2008. 195 Hurtado PR, Jeffs L, Nitschke J, Patel M, Sarvestani G, Cassidy J, 178 Hodge S, Hodge G, Holmes M, Reynolds PN. New apoptosis research Hissaria P, Gillis D, Peh CA. CpG oligodeoxynucleotide stimulates in respiratory disease. In: Cell Apoptosis Research Progress, Nova production of anti-neutrophil cytoplasmic antibodies in ANCA Science Publishers, Eds Fenton RH and Burnside CV, 2008. associated vasculitis. BMC Immunology 9:34, 2008. 179 Hodge S, Hodge G, Jersmann H, Matthews G, Ahern J, Holmes M, 196 Ingman WV, Robertson SA. Mammary gland development in Reynolds PN. Azithromycin improves macrophage phagocytic function transforming growth factor beta1 null mutant mice: Systemic and and expression of mannose receptor in COPD. American Journal of epithelial effects. Biology of Reproduction 79:711-717, 2008. Respiratory and Critical Care Medicine 178:139-148, 2008. 197 Irla M, Hugues S, Gill J, Nitta T, Hikosaka Y, Williams IR, Hubert FX, 180 Hodge SJ, Reynolds PN. The impact of defective clearance of apoptotic Scott HS, Takahama Y, Holländer GA, Reith W. Autoantigen-specific cells in the pathogenesis of chronic lung diseases: chronic obstructive interactions with CD4+ thymocytes control mature medullary thymic pulmonary disease, asthma and cystic fibrosis. In: Phagocytosis of epithelial cell cellularity. Immunity 29:451-463, 2008. dying cells: from molecular mechanisms to human diseases. Chapter 198 Jain R, Chen JY, Butcher AR, Casson R, Selva D. Subconjunctival Loa 12, Springer Publishers, 2008. loa worm. International Journal of Infectious Diseases 12:e133-e135, 181 Hoffmann P, Woon J, Rowley KG, Karschimkus C, Nelson CL, 2008. Dragicevic G, O’Neal D, Wilson A, Croft KD, Mori TA, Kemp BE, Best 199 Jain R, Prabhakaran VC, Huilgol SC, Gehling N, James CL, Selva D. JD, Jenkins AJ. Glutathionyl haemoglobin is not increased in diabetes Eccrine porocarcinoma of the upper eyelid. Ophthalmic Plastic & nor related to glycaemia, complications, dyslipidaemia, inflammation Reconstructive Surgery 24:221-223, 2008. or other measures of oxidative stress. Diabetes Research & Clinical Practice 80:e1-3, 2008. 200 James HM, Gillis D, Hissaria P, Lester S, Somogyi AA, Cleland LG, Proudman SM. Common polymorphisms in the folate pathway predict 182 Holloway RH, Sifrim DA. The acid pocket and its relevance to reflux efficacy of combination regimens containing methotrexate and disease. Gut 57:285-286, 2008. sulfasalazine in early rheumatoid arthritis. Journal of Rheumatology 183 Holm R, Knopp S, Kumar R, Lee J, Nesland JM, Trope C, Callen DF. 35:562-571, 2008. Expression of ZNF652, a novel zinc finger protein, in vulvar 201 Jamieson GG. The price of doubt is esophageal adenocarcinoma. carcinomas and its relation to prognosis. Journal of Clinical Pathology Annals of Surgery 247:559-560, 2008. 61:59-63, 2008. 202 Janovská A, Hatzinikolas G, Staikopoulos V, McInerney J, Mano M, 184 Holtmann G, Gapasin J. Failed therapy and directions for the future in Wittert GA. AMPK and ACC phosphorylation: Effect of leptin, muscle dyspepsia. Digestive Diseases 26:218-224, 2008. fibre type and obesity. Molecular & Cellular Endocrinology 284:1-10, 185 Horowitz M, Vilsbøll T, Zdravkovic M, Hammer M, Madsbad S. 2008. Patient-reported rating of gastrointestinal adverse effects during 203 Jarrett M, McMahon M, Stiller K. 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53 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

204 Jayasinghe UW, Proudfoot J, Holton C, Davies GP, Amoroso C, Bubner 221 Keogh JB, Clifton P. The effect of meal replacements high in T, Beilby J, Harris MF. Chronically ill Australians’ satisfaction with glycomacropeptide on weight loss and markers of cardiovascular accessibility and patient-centredness. International Journal for Quality disease risk. American Journal of Clinical Nutrition 87:1602-1605, in Health Care 20:105-114, 2008. 2008. 205 Jesudason D, Wittert G. Endocannabinoid system in food intake and 222 Keogh JB, Clifton PM. Salt intake and health in the Australian metabolic regulation. Current Opinion in Lipidology 19:344-348, population. Medical Journal of Australia 189:526, 2008. 2008. 223 Kerfoot SM, Andonegui G, Bonder CS, Liu L. Exogenous stromal cell 206 Jilbert AR, Litwin S, Mason WS. Pathogenesis of Hepatitis B Virus derived factor-1 induces modest leukocyte recruitment in vivo. Infections. In: Hepatitis B Virus Human Virus Guide, 2nd Edition, American Journal of Physiology Heart and Circulatory Physiology Locarnini S, Lai CL, editors, International Medical Press, Chapter 7, 294:H2524-2534, 2008. 2008. 224 Kimber TE, Thompson PD, Kiley MA. Resolution of dopamine 207 Jilbert AR, Mason WS, Kann M. Hepatitis B virus replication. In: dysregulation syndrome following cessation of dopamine agonist Hepatitis B Virus Human Virus Guide, 2nd Edition, Locarnini S, Lai therapy in Parkinson’s disease. Journal of Clinical Neuroscience CL, editors, International Medical Press, Chapter 2, 2008. 15:205-208, 2008. 208 Jilbert AR, Mason WS. Hepadnaviruses of Birds. In: Encyclopedia of 225 King RA, Noakes M, Bird AR, et al. An extruded breakfast cereal made Virology, Mahy BWJ, Van Regenmortel MHV, editors, Elsevier, Oxford, from a high amylose barley cultivar has a low glycemic index and 3rd edition, pp 327-335, 2008. lower plasma insulin response than one made from a standard barley. 209 John B, Stiles MK, Kuklik P, Chandy ST, Young GD, Mackenzie L, Journal of Cereal Science 48:526-530, 2008. Szumowski L, Joseph G, Jose J, Worthley SG, Kalman JM, Sanders P. 226 Kirby CN, Piterman L, Nelson MR, Dent J. Gastro-oesophageal reflux Electrical remodelling of the left and right atria due to rheumatic mitral disease – Impact of guidelines on GP management. Australian Family stenosis. European Heart Journal 29:2234-2243, 2008. Physician 37:73-77, 2008. 210 Johnson NC, Dillard ME, Baluk P, McDonald DM, Harvey NL, Frase 227 Kisand K, Link M, Wolff AS, Meager A, Tserel L, Org T, Murumagi A, SL, Oliver G. Lymphatic endothelial cell identity is reversible and its Uibo R, Willcox N, Trebusak Podkrajsek K, Battelino T, Lobell A, maintenance requires Prox1 activity. Genes & Development 22:3282- Kampe O, Lima K, Meloni A, Ergun-Longmire B, Maclaren NK, 3291, 2008. Perheentupa J, Krohn KJ, Scott HS, Husebye ES, Peterson P. Interferon 211 Jones BR, El-Merhibi A, Ngo SN, Stupans I, McKinnon RA. Hepatic autoantibodies associated with AIRE-deficiency decrease the cytochrome P450 enzymes belonging to the CYP2C subfamily from an expression of IFN-stimulated genes. Blood 112:2657-2666, 2008. Australian marsupial, the koala (Phascolarctos cinereus). Comparative 228 Kleinig TJ, Harley H, Thompson PD. Neurological deterioration during biochemistry and physiology. Toxicology & Pharmacology: CBP treatment in Wilson’s disease: question. Journal of Clinical 148:230-237, 2008. Neuroscience 15:575, 607, 2008. 212 Jordan SJ, Green AC, Whiteman DC, Moore SP, Bain CJ, Gertig DM, 229 Kleinig TJ, Kiley M, Thompson PD. Acute convexity subarachnoid Webb PM; Australian Cancer Study Group (ovarian cancer); Australian haemorrhage: a cause of aura-like symptoms in the elderly. Ovarian Cancer Study Group. Serous ovarian, fallopian tube and Cephalalgia 28:658-663, 2008. primary peritoneal cancers: a comparative epidemiological analysis. 230 Kleinig TJ, Thompson PD, Matar W, Duggins A, Kimber TE, Morris JG, International Journal of Cancer 122:1598-1603, 2008. Kneebone CS, Blumbergs PC. The distinctive movement disorder of 213 Juhasz AL, Smith E, Weber J, Naidu R, Rees M, Rofe A, Kuchel T, ovarian teratoma-associated encephalitis. Movement Disorders Sansom L. Effect of soil ageing on in vivo arsenic bioavailability in two 23:1256-1261, 2008. dissimilar soils. Chemosphere 71:2180-2186, 2008. 231 Koeppel A, Perry EB, Sikorski J, Krizanc D, Warner A, Ward DM, 214 Juhasz AL, Smith E, Weber J, Rees M, Rofe A, Kuchel T, Sansom L, Rooney AP, Brambilla E, Connor N, Ratcliff RM, Nevo E, Cohan FM. Naidu R. Application of an in vivo swine model for the determination of Identifying the fundamental units of bacterial diversity: a paradigm shift arsenic bioavailability in contaminated vegetables. Chemosphere to incorporate ecology into bacterial systematics. Proceedings of the 71:1963-1969, 2008. National Academy of Sciences USA 105:2504-2509, 2008. 215 Kawakami K, Ooyama A, Ruszkiewicz A, Jin M, Watanabe G, Moore J, 232 Kohler RE, Comerford I, Townley S, Haylock-Jacobs S, Clark-Lewis I, Oka T, Iacopetta B, Minamoto T. Low expression of gamma-glutamyl McColl SR. Antagonism of the chemokine receptors CXCR3 and hydrolase mRNA in primary colorectal cancer with the CpG island CXCR4 reduces the pathology of experimental autoimmune methylator phenotype. British Journal of Cancer 98:1555-1561, 2008. encephalomyelitis. Brain Pathology 18:504-516, 2008. 216 Kearney BJ, Blamey SL. Health technology assessment in Australia. 233 Kojecky V, Bernatek J, Horowitz M, Zemek S, Bakala J, Hep A. Medical Journal of Australia 188:495, 2008. Prevalence and determinants of delayed gastric emptying in 217 Keefe D, Anthony L. Tyrosine kinase inhibitors and gut toxicity: a new hospitalised Type 2 diabetic patients. World Journal of era in supportive care. Current Opinion in Supportive and Palliative Gastroenterology 14:1564-1569, 2008. Care 2:19-21, 2008. 234 Kollias J, Davies G, Bochner MA, Gill PG. Clinical impact of 218 Keefe DM, Sonis ST, Bowen JM. Emerging drugs for chemotherapy oncoplastic surgery in a specialist breast practice. ANZ Journal of induced mucositis. Expert Opinion on Emerging Drugs 13:511-522, Surgery 78:269-272, 2008. 2008. 235 Kont V, Laan M, Kisand K, Merits A, Scott HS, Peterson P. Modulation 219 Keefe DMK, Bowen JM, Gibson RJ. Use of project teams in preclinical of Aire regulates the expression of tissue-restricted antigens. development. In: Preclinical Development Handbook: Toxicology, Gad Molecular Immunology 45:25-33, 2008. SC, editor, Wiley, Chapter 2, 2008. 236 Kumar R, Cheney KM, McKirdy R, Neilsen PM, Schulz RB, Lee J, 220 Keogh JB, Brinkworth GD, Noakes M, Belobrajdic DP, Buckley JD, Cohen J, Booker GW, Callen DF. CBFA2T3-ZNF652 corepressor Clifton PM. Effects of weight loss from a very-low-carbohydrate diet complex regulates transcription of the E-box gene HEB. Journal of on endothelial function and markers of cardiovascular disease risk in Biological Chemistry 283:19026-19038, 2008. subjects with abdominal obesity. American Journal of Clinical Nutrition 87:567-576, 2008.

54 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

237 Kumar S, Pérez WS, Zhang MJ, Ballen K, Bashey A, To LB, Bredeson 251 Ledgard JP, van Hal S, Greenwood JE. Primary cutaneous CN, Cairo MS, Elfenbein GJ, Freytes CO, Gale RP, Gibson J, Kyle RA, zygomycosis in a burns patient: A review. Journal of Burn Care & Lacy MQ, Lazarus HM, McCarthy PL, Milone GA, Moreb JS, Research 29:286-290, 2008. Pavlovsky S, Reece DE, Vesole DH, Wiernik PH, Hari P. Comparable 252 Lee SH, Ho SJ, Thomas DT, Giri P, Lee H, Sia H, To LB, Sullivan TR. A outcomes in nonsecretory and secretory multiple myeloma after partial nucleated differential cell count of the bone marrow aspirate that autologous stem cell transplantation. Biology of Blood & Marrow is independent of peripheral blood dilution. International Journal of Transplantation 14:1134-1140, 2008. Laboratory Hematology 30:473-479, 2008. 238 Kuo P, Chaikomin R, Pilichiewicz A, O’Donovan D, Wishart JM, Meyer 253 Leong DP, Dundon BK, Puri R, Yeend RA. Very late stent fracture JH, Jones KL, Feinle-Bisset C, Horowitz M, Rayner CK. Transient, early associated with a sirolimus-eluting stent. Heart, Lung & Circulation release of glucagon-like peptide-1 during low rates of intraduodenal 17:426-428, 2008. glucose delivery. Regulatory Peptides 146:1-3, 2008. 254 Leong DP, Dundon BK, Steele PM. Unilateral pulmonary vein stenosis 239 Kuo YH, Roos D, Brophy BP. Linear accelerator radiosurgery for secondary to idiopathic fibrosing mediastinitis. Heart 94:776, 2008. treatment of vestibular schwannomas in neurofibromatosis 2. Journal 255 Lester SE, McLure C, Williamson J, Bardy P, Rischmueller M, Dawkins of Clinical Neuroscience 15:744-748, 2008. RL. Epistasis between MHC and the RCA{alpha} block in primary 240 Kurmis AP, Slavotinek JP, Barber C, Fazzalari NL. Determining disk Sjogren’s syndrome. Annals of the Rheumatic Diseases 67:849-854, hydration status with a MnCl2-based MR model. Radiologic 2008. Technology 79:507-513, 2008. 256 Leyden J, Kleinig T. The role of the basal ganglia in data processing. 241 La Vincente SF, White JM, Somogyi AA, Bochner F, Chapleo CB. Medical Hypotheses 71:61-64, 2008. Enhanced buprenorphine analgesia with the addition of ultra-low-dose 257 Li JY, Yong TY, Grove DI, Coates PT. Successful control of naloxone in healthy subjects. Clinical Pharmacology & Therapeutics Scedosporium prolificans septic arthritis and probable osteomyelitis 83:144-152, 2008. without radical surgery in a long-term renal transplant recipient. 242 Labrinidis A, Liapis V, Thai le M, Atkins GJ, Vincent C, Hay S, Sims Transplant Infectious Disease 10:63-65, 2008. NA, Zannettino AC, Findlay DM, Evdokiou A. Does Apo2L/TRAIL play 258 Li X, Stankovic M, Bonder CS, Hahn CN, Parsons M, Pitson SM, Xia any physiologic role in osteoclastogenesis? Blood 111:5411-5412, P, Proia RL, Vadas MA, Gamble JR. Basal and angiopoietin-1- 2008. mediated endothelial permeability is regulated by sphingosine kinase- 243 Laforest C, Leibovitch I, Selva D, Crompton J, Haan E. Ocular 1. Blood 111:3489-3497, 2008. colobomata, polydactyly, cleft palate and panhypopituitarism: a new 259 Lidbury BA, Rulli NE, Suhrbier A, Smith PN, McColl SR, Cunningham syndrome. Clinical Dysmorphology 17:87-90, 2008. AL, Tarkowski A, van Rooijen N, Fraser RJ, Mahalingam S. 244 Lam A, Hamilton-Bruce MA, Jannes J, Koblar SA. Cerebral small Macrophage-derived proinflammatory factors contribute to the vessel disease: genetic risk assessment for prevention and treatment. development of arthritis and myositis after infection with an Molecular Diagnosis & Therapy 12:145-156, 2008. arthrogenic alphavirus. Journal of Infectious Diseases 197:1585-1593, 245 Lau DH, Wilson L, Stiles MK, John B, Shashidhar , Dimitri H, Brooks 2008. AG, Young GD, Sanders P. Defibrillator reset by radiotherapy. 260 Limawararut V, Valenzuela AA, Sullivan TJ, McNab AA, Malhotra R, International Journal of Cardiology 130:e37-38, 2008. Davis G, Jones N, Selva D. Cerebrospinal fluid leaks in orbital and 246 Laurence C, Gialamas A, Yelland L, Bubner T, Ryan P, Willson K, lacrimal surgery. Survey of Ophthalmology 53:274-284, 2008. Glastonbury B, Gill J, Shephard M, Beilby J, Trial Management 261 Limaye V. The role of sphingosine kinase and sphingosine-1 Committee P. A pragmatic cluster randomised controlled trial to phosphate in the regulation of endothelial cell biology. Endothelium evaluate the safety, clinical effectiveness, cost effectiveness and 15:101-112, 2008. satisfaction with point of care testing in a general practice setting – 262 Limaye VS, Cassidy J, Scott G, Roberts-Thomson PJ, Gillis D. Anti rationale, design and baseline characteristics. Trials 9:50, 2008. Ro52 antibodies, antisynthetase antibodies, and antisynthetase 247 Layman DK, Clifton P, Gannon MC, Krauss RM, Nuttall FQ. Protein in syndrome. Clinical Rheumatology 27:521-523, 2008. optimal health: heart disease and type 2 diabetes. American Journal of 263 Lin NH, Gronthos S, Bartold PM. Stem cells and periodontal Clinical Nutrition 87:1571S-1575S, 2008. regeneration. Australian Dental Journal 53:108-121, 2008. 248 Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, 264 Lin NH, Menicanin D, Mrozik K, Gronthos S, Bartold PM. Putative Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, stem cells in regenerating human periodontium. Journal of Bacigalupo A, Fibbe W, Ringden O, on behalf of the Developmental Periodontal Research 43:514-523, 2008. Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid- 265 Lindström E, Brusberg M, Hughes PA, Martin CM, Brierley SM, Phillis resistant, severe, acute graft-versus-host disease: a phase II study. BD, Martinsson R, Abrahamsson C, Larsson H, Martinez V, Blackshaw Lancet 371:1579-1586, 2008. LA. Involvement of metabotropic glutamate 5 receptor in visceral pain. Pain 137:295-305, 2008. 249 Le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, Apperley JF, Larson RA, Abruzzese E, O'Brien SG, Kuliczkowski K, 266 Ling KH, Hewitt, CA, Smyth GK, Kinkel SA, Scott HS. High-throughput Hochhaus A, Mahon FX, Saglio G, Gobbi M, Kwong YL, Baccarani M, and complex gene expression validation using the Universal ® Hughes T, Martinelli G, Radich JP, Zheng M, Shou Y, Kantarjian H. ProbeLibrary and the LightCycler 480 system. Biochemica 2:23-26, Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine 2008. kinase inhibitor, is active in patients with imatinib-resistant or 267 Linnebjerg H, Park S, Kothare PA, Trautmann ME, Mace K, Fineman –intolerant accelerated-phase chronic myelogenous leukemia. Blood M, Wilding I, Nauck M, Horowitz M. Effect of exenatide on gastric 111:1834-1839, 2008. emptying and relationship to postprandial glycemia in type 2 diabetes. 250 Leclercq TM, Moretti PA, Vadas MA, Pitson SM. Eukaryotic elongation Regulatory Peptides 151:123-129, 2008. factor 1a interacts with sphingosine kinase and directly enhances its 268 Little TJ, Feltrin KL, Horowitz M, Meyer JH, Wishart JM, Chapman IM, catalytic activity. Journal of Biological Chemistry 283:9606-9614, Feinle-Bisset C. A high-fat diet raises fasting plasma CCK, but does 2008. not affect upper gut motility, PYY and ghrelin, or energy intake during CCK-8 infusion in lean men. American Journal of Physiology. Regulatory, Integrative & Comparative Physiology 294:R45-51, 2008.

55 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

269 Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi 287 McCann Mortimer P, Ward L, Winefield H. Successful ageing by S, Wang S. Periodontal ligament stem cell-mediated treatment for whose definition? Views of older, spiritually affiliated women. periodontitis in miniature swine. Stem Cells 26:1065-1073, 2008. Australasian Journal of Ageing 27:200-204, 2008. 270 Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM. 288 McCartney EM, Semendric L, Helbig KJ, Hinze S, Jones B, Weinman Characterisation of mucosal changes in the alimentary tract following SA, Beard MR. Alcohol metabolism increases the replication of administration of irinotecan: implications for the pathobiology of Hepatitis C virus and attenuates the antiviral action of interferon. mucositis. Cancer Chemotherapy & Pharmacology 62:33-41, 2008. Journal of Infectious Diseases 198:1766-1775, 2008. 271 Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM. 289 McGregor C, Srisurapanont M, Mitchell A, Longo MC, Cahill S, White Serum levels of NF- kappaB and pro-inflammatory cytokines following JM. Psychometric evaluation of the amphetamine cessation symptom administration of mucotoxic drugs. Cancer Biology & Therapy 7:1139- assessment. Journal of Substance Abuse Treatment 34:443-449, 2008. 1145, 2008. 290 Melino M, Hii CS, McColl SR, Ferrante A. The effect of the JNK 272 Longstreet DA, Heath DL, Savage I, Vink R, Panaretto KS. Estimated inhibitor, JIP peptide, on human T lymphocyte proliferation and nutrient intake of urban indigenous patients in a lifestyle intervention cytokine production. Journal of Immunology 181:7300-7306, 2008. program. Nutrition & Dietetics 65:128-133, 2008. 291 Melrose J, Smith SM, Little CB, Moore RJ, Vernon-Roberts B, Fraser 273 Lonic A, Barry EF, Quach C, Kobe B, Saunders N, Guthridge MA. RD. Recent advances in annular pathobiology provide insights into FGFR2 phosphorylation on Serine 779 couples to 14-3-3 and rim-lesion mediated intervertebral disc degeneration and potential new regulates cell survival and proliferation. Molecular & Cellular Biology approaches to annular repair strategies. European Spine Journal 28:3372-3385, 2008. 17:1131-1148, 2008. 274 Low SC, Greenwood JE. Capnocytophaga canimorsus: infection, 292 Merritt MA, Green AC, Nagle CM, Webb PM; Australian Cancer Study septicaemia, recovery and reconstruction. Journal of Medical (Ovarian Cancer) and Australian Ovarian Cancer Study Group. The Microbiology 57:901-903, 2008. Australian Ovarian Cancer Study Group comprises: Clinical 275 Luke C, Koczwara B, Karapetis C, Pittman K, Price T, Kotasek D, Collaborators: SA: Davy M, Hall C, Dodd T, Healy T, Pittman K, Beckmann K, Brown MP, Roder D. Exploring the epidemiological Henderson D, Hyde S, Miller J, J Pierdes J. Talcum powder, chronic characteristics of cancers of unknown primary site in an Australian pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian population: implications for research and clinical care. Australian and cancer. International Journal of Cancer 122:170-176, 2008. New Zealand Journal of Public Health 32:383-389, 2008. 293 Metcalf RG, Sanders P, James MJ, Cleland LG, Young GD. Effect of 276 Luke CG, Yeoh E, Roder DM. Exploring trends in laryngeal cancer dietary n-3 polyunsaturated fatty acids on the inducibility of ventricular incidence, mortality and survival: implications for research and cancer tachycardia in patients with ischemic cardiomyopathy. American control. Asian Pacific Journal of Cancer Prevention 9:397-402, 2008. Journal of Cardiology 101:758-761, 2008. 277 Lumb R, Bastian I, Gilpin C, Jelfs P, Keehner T, Sievers A. Tuberculosis 294 Michaud J, Simpson KM, Escher R, Buchet-Poyau K, Beissbarth T, in Australia: bacteriologically confirmed cases and drug resistance, Carmichael C, Ritchie ME, Schutz F, Cannon P, Liu M, Shen X, Ito Y, 2006 a report of the Australian Mycobacterium Reference Laboratory Raskind WH, Horwitz MS, Osato M, Turner DR, Speed TP, Kavallaris Network. Communicable Diseases Intelligence 32:12-17, 2008. M, Smyth GK, Scott HS. Integrative analysis of RUNX1 downstream pathways and target genes. BMC Genomics 9:363, 2008. 278 Luscombe-Marsh ND, Smeets AJ, Westerterp-Plantenga MS. Taste sensitivity for monosodium glutamate and an increased liking of 295 Mikocka-Walus AA, Turnbull DA, Andrews JM, Moulding NT, dietary protein. British Journal of Nutrition 99:904-908, 2008. Holtmann GJ. The effect of functional gastrointestinal disorders (FGIDs) on psychological co-morbidity and quality of life in patients 279 Luty AA, Kwok JB, Thompson EM, Blumbergs P, Brooks WS, Loy CT, with inflammatory bowel disease (IBD). Alimentary Pharmacology and Dobson-Stone C, Panegyres PK, Hecker J, Nicholson GA, Halliday Therapeutics 28:475-483, 2008. GM, Schofield PR. Pedigree with frontotemporal lobar degeneration- motor neuron disease and Tar DNA binding protein-43 positive 296 Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Holtmann neuropathology: genetic linkage to chromosome 9. BMC Neurology GJ, Andrews JM. Does psychological status influence clinical 8:32, 2008. outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: An observational cohort 280 Mabarrack NH, Turner NL, Mayrhofer G. Recent thymic origin, prospective study. Biopsychosocial Medicine 2:11, 2008. differentiation, and turnover of regulatory T cells. Journal of Leukocyte Biology 84:1287-1297, 2008. 297 Miles LA, Wun KS, Crespi GA, Fodero-Tavoletti MT, Galatis D, Bagley CJ, Beyreuther K, Masters CL, Cappai R, McKinstry WJ, Barnham KJ, 281 Madge SN, Prabhakaran VC, Shome D, Kim U, Honavar S, Selva D. Parker MW. Amyloid-beta-anti-amyloid-beta complex structure reveals Orbital tuberculosis: a review of the literature. Orbit 27:267-277, 2008. an extended conformation in the immunodominant B-cell epitope. 282 Mangat P, Ravindran J, Cleland L, Limaye V. A case of longitudinally Journal of Molecular Biology 377:181-192, 2008. extensive transverse myelitis (LETM): neuromyelitis optica. Clinical 298 Miller DS, Boyle D, Feng F, Reaiche GY, Kotlarski I, Colonno R, Jilbert Rheumatology 27 Suppl 2:S67-69, 2008. AR. Antiviral therapy with entecavir combined with post-exposure 283 Mangat P, Whittle S, Cleland L, Limaye V. Digital vasculitis: a late “prime-boost” vaccination eliminates duck hepatitis B virus-infected complication of anti-tumour necrosis factor alpha therapy. Clinical hepatocytes and prevents the development of persistent infection. Rheumatology 27:1593-1595, 2008. Virology 373:329-341, 2008. 284 Manning JA, Colussi PA, Koblar SA, Kumar S. Nedd1 expression as a 299 Mittal RR, McKinnon RA, Sorich MJ. Effect of steric molecular field marker of dynamic centrosomal localization during mouse embryonic settings on CoMFA predictivity. Journal of Molecular Modelling 14:59- development. Histochemistry and Cell Biology 129:751-764, 2008. 67, 2008. 285 Martin DM, Wittert G, Burns NR, McPherson J. Endogenous 300 Modlin IM, Hunt RH, Malfertheiner P, Moayyedi P, Quigley EM, testosterone levels, mental rotation performance, and constituent Tytgat GN, Tack J, Holtmann G, Moss SF. Non-erosive reflux disease- abilities in middle-to-older aged men. Hormones & Behaviour 53:431- defining the entity and delineating the management. Digestion 78 441, 2008. Suppl 1:1-5, 2008. 286 Martin SA, Haren MT, Taylor AW, Middleton SM, Wittert GA, Florey Adelaide Male Ageing Study MO. Chronic disease prevalence and associations in a cohort of Australian men: The Florey Adelaide Male Ageing Study (FAMAS). BMC Public Health 8:261, 2008.

56 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

301 Moffatt P, Gaumond MH, Salois P, Sellin K, Bessette MC, Godin E, 318 Niscola P, Scaramucci L, Romani C, Cupelli L, Tendas A, Dentamaro T, Tambasco de Oliveira P, Atkins GJ, Nanci A, Thomas G. Bril, a novel Ales M, Giovannini M, Piccioni D, Siniscalchi A, Tolu B, Perrotti A, bone-specific modulator of mineralisation. Journal of Bone & Mineral Keefe D, de Fabritiis P. Mucositis in the treatment of haematological Research 23:1497-1508, 2008. malignancies. Annals of Oncology 19:Suppl 7:41-45, 2008. 302 Molaee P, Dundon BK. Mitochondrial encephalomyopathy, lactic 319 Noakes M, Clifton P. Health and environmental benefits of the CSIRO acidosis and stroke-like episodes in a 69-year-old woman. Internal total wellbeing diet. Nutrition & Dietetics 65:232-233, 2008. Medicine Journal 38:451-452, 2008. 320 Nordin BE, Prince RL, Tucker GR. Bone density and fracture risk. 303 Moran LJ, Noakes M, Clifton PM, Norman RJ, Fenech MF. Genome Medical Journal of Australia 189:7-8, 2008. instability is increased in lymphocytes of women with polycystic ovary 321 Nordin BE. Redefining Osteoporosis. Calcified Tissue International syndrome and is correlated with insulin resistance. Mutation Research 83:365-367, 2008. 639:55-63, 2008. 322 Norman J, Shapter JG, Short K, Smith LJ, Fazzalari NL. 304 Mu FT, Andrews RK, Arthur JF, Munday AD, Cranmer SL, Jackson SP, Micromechanical properties of human trabecular bone: a hierarchical Stomski FC, Lopez AF, Berndt MC. A functional 14-3-3{zeta}- investigation using nanoindentation. Journal of Biomedical Materials independent association of PI3-kinase with glycoprotein Ib{alpha}, the Research A 87:196-202, 2008. major ligand-binding subunit of the platelet glycoprotein Ib-IX-V 323 Norman MU, Hwang J, Hulliger S, Bonder CS, Yamanouchi J, complex. Blood 111:4580-4587, 2008. Santamaria P, Kubes P. Mast cells regulate the magnitude and the 305 Mudiyanselage SY, Prabhakaran VC, Davis GJ, Selva D. Metastatic cytokine microenvironment of the contact hypersensitivity response. renal cell carcinoma presenting as a circumscribed orbital mass. American Journal of Pathology 172:1638-1649, 2008. European Journal of Ophthalmology 18:483-485, 2008. 324 Nossent JC, Lester S, Zahra D, Mackay CR, Rischmueller M. 306 Muecke JS, Newland HS, Ryan P, Ramsay E, Aung M, Myint S, Polymorphism in the 5' regulatory region of the B-lymphocyte Esmail-Zadeh R, Zborowska B, Selva D. Awareness of diabetic eye activating factor gene is associated with the Ro/La autoantibody disease among general practitioners and diabetic patients in Yangon, response and serum BAFF levels in primary Sjogren’s syndrome. Myanmar. Clinical & Experimental Ophthalmology 36:265-273, 2008. Rheumatology (Oxford) 47:1311-1316, 2008. 307 Muhlhausler BS, Ritorto V, Schultz C, Chatterton BE, Duffield JA, 325 Oh SY, Cornell B, Smith D, Higgins G, Burrell CJ, Kok TW. Rapid McMillen IC. Birth weight and gender determine expression of detection of influenza A virus in clinical samples using an ion channel adipogenic, lipogenic and adipokine genes in perirenal adipose tissue switch biosensor. Biosensors & Bioelectronics 23:1161-1165, 2008. in the young adult sheep. Domestic Animal Endocrinology 35:46-57, 326 O’Leary S, Lloyd ML, Shellam GR, Robertson SA. Immunization with 2008. Recombinant murine cytomegalovirus expressing murine Zona 308 Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, White Pellucida 3 causes permanent infertility in BALB/c mice due to follicle D, Hughes TP, Le Beau MM, Pui C-H, Relling MV, Shurtleleff SA, depletion and ovulation failure. Biology of Reproduction 79:849-860, Downing JR. BCR-ABL1 lymphoblastic leukaemia is characterised by 2008. the deletion of Ikaros. Nature 453:110-114, 2008. 327 Page AJ, O’Donnell TA, Blackshaw LA. Opioid modulation of ferret 309 Need AG, Nordin BE. Misconceptions – Vitamin D insufficiency causes vagal afferent mechanosensitivity. American Journal of Physiology. malabsorption of calcium. Bone 42:1021-1024, 2008. Gastrointestinal & Liver Physiology 294:G963-970, 2008. 310 Need AG, Nordin C. Seasonal variation in bone histomorphometry. 328 Pakrou N, Casson R, Fung S, Ferdowsi N, Lee G, Selva D. South Journal of Bone & Mineral Research 23:302, 2008. Australian adolescent ophthalmic sun protective behaviours. Eye 311 Need AG, O’Loughlin PD, Morris HA, Coates PS, Horowitz M, Nordin 22:808-814, 2008. BE. Vitamin D metabolites and calcium absorption in severe Vitamin D 329 Parkinson IH, Badiei A, Fazzalari NL. Variation in segmentation of bone deficiency. Journal of Bone & Mineral Research 23:1859-1863, 2008. from micro-CT imaging: implications for quantitative morphometric 312 Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, analysis. Australasian Physical & Engineering Sciences in Medicine Powell JA, Kumar R, Callen DF. Identification of ANKRD11 as a p53 31:160-164, 2008. coactivator. Journal of Cell Science 121:3541-3552, 2008. 330 Parkinson IH, Fazzalari NL. Whole bone geometry and bone quality in 313 Nestor P, Galletly C. The employment of consumers in mental health distal forearm fracture. Journal of Orthopaedic Trauma 22:S59-65, services: politically correct tokenism or genuinely useful? Australasian 2008. Psychiatry 16:344-347, 2008. 331 Paterson EL, Kolesnikoff N, Gregory PA, Bert AG, Khew-Goodall Y, 314 Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Burgstad C, Ching K, Goodall GJ. The microRNA-200 family regulates epithelial to Bellon M, Holloway RH. The effects of sedation on gastric emptying mesenchymal transition. Scientific World Journal 8:901-904, 2008. and intra-gastric meal distribution in critical illness. Intensive Care 332 Pearce KL, Noakes M, Keogh J, Clifton PM. Effect of carbohydrate Medicine 34:454-460, 2008. distribution on postprandial glucose peaks with the use of continuous 315 Nguyen NQ, Ching K, Fraser RJ, Chapman MJ, Holloway RH. Risk of glucose monitoring in type 2 diabetes. American Journal of Clinical Clostridium difficile diarrhoea in critically ill patients treated with Nutrition 87:638-644, 2008. erythromycin-based prokinetic therapy for feed intolerance. Intensive 333 Pham D, Moretti P, Goodall G, Pitson S. Attenuation of leakiness in Care Medicine 34:169-173, 2008. doxycycline-inducible expression via incorporation of 3' AU-rich 316 Nguyen NQ, Fraser RJ, Bryant LK, Burgstad C, Chapman MJ, Bellon mRNA destabilizing elements. Biotechniques 45:155-162, 2008. M, Wishart J, Holloway RH, Horowitz M. The impact of delaying 334 Philp LK, Muhlhausler BS, Janovska A, Wittert GA, Duffield JA, enteral feeding on gastric emptying, plasma cholecystokinin, and McMillen IC. Maternal overnutrition suppresses the phosphorylation peptide YY concentrations in critically ill patients. Critical Care of 5'-AMP activated protein kinase (AMPK) in liver, but not skeletal Medicine 36:1469-1474, 2008. muscle, in fetal and neonatal sheep. American Journal of Physiology. 317 Nguyen NQ, Fraser RJ, Bryant LK, Chapman M, Holloway RH. Regulatory, Integrative & Comparative Physiology 295:R1982-1990, Diminished functional association between proximal and distal gastric 2008. motility in critically ill patients. Intensive Care Medicine 34:1246- 1255, 2008.

57 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

335 Philpott H, Hissaria P, Warrren L, Singhal N, Brown M, Proudman S, 354 Puri R, Dundon BK, Worthley MI, Worthley SG, Brown MA. Drug Cleland L, Gillis D. Eosinophilic fasciitis as a paraneoplastic eluting stent treatment of a radiation-induced left internal mammary phenomenon associated with metastatic colorectal carcinoma. arterial graft stenosis. Circulation Journal 72:1904-1906, 2008. Australasian Journal of Dermatology 49:27-29, 2008. 355 Puri R, Dundon BK, Worthley SG, Worthley MI. Thebesian coronary 336 Philpott H, Kette F, Hissaria P, Gillis D, Smith W. Chronic urticaria: the system. Heart Lung & Circulation 17:414-415, 2008. autoimmune paradigm. Internal Medicine Journal 38:852-857, 2008. 356 Putz U, Howitt J, Lackovic J, Foot N, Kumar S, Silke J, Tan SS. 337 Phumoonna T, Barton MD, Vanniasinkam T, Heuzenroeder MW. Nedd4-family interacting protein 1 (Ndfip1) is required for the Chimeric vapA/groEL2 DNA vaccines enhance clearance of exosomal secretion of Nedd4-family proteins. Journal of Biological Rhodococcus equi in aerosol challenged C3H/He mice. Vaccine Chemistry 283:32621-322627, 2008. 26:2457-2465, 2008. 357 Quan C, Talley NJ, Jones MP, Howell S, Horowitz M. Gastrointestinal 338 Pilichiewicz AN, Feltrin KL, Horowitz M, Holtmann G, Wishart JM, symptoms and glycemic control in diabetes mellitus: a longitudinal Jones KL, Talley NJ, Feinle-Bisset C. Functional dyspepsia is population study. European Journal of Gastroenterology and associated with a greater symptomatic response to fat but not Hepatology 20:888-897, 2008. carbohydrate, increased fasting and postprandial CCK, and diminished 358 Quan C, Talley NJ, Jones MP, Spies J, Horowitz M. Gain and loss of PYY. American Journal of Gastroenterology 103:2613-2623, 2008. gastrointestinal symptoms in diabetes mellitus: associations with 339 Pitson SM, Goodall GJ, Guthridge MA. Science amongst the vines. psychiatric disease, glycemic control, and autonomic neuropathy over Meeting on Signalling Systems. EMBO Reports 9:425-428, 2008. 2 years of follow-up. American Journal of Gastroenterology 103:2023- 340 Pitt LA, Hubert FX, Scott HS, Godfrey DI, Berzins SP. NKT cell 2030, 2008. development in the absence of the autoimmune regulator gene (Aire). 359 Rangappa P. History of analgesia and regional anaesthesia through European Journal of Immunology 38:2689-2696, 2008. philately. Anaesthia & Intensive Care 36 Suppl 1:12-18, 2008. 341 Ponniah A, Shakib S, Doecke CJ, Boyce M, Angley M. Post-discharge 360 Reuter SE, Faull RJ, Evans AM. L-carnitine supplementation in the medication reviews for patients with heart failure: a pilot study. dialysis population: Are Australian patients missing out? (Review Pharmacy World & Science 30:810-815, 2008. Article). Nephrology (Carlton) 13:3-16, 2008. 342 Pountney DL, Raftery MJ, Chegini F, Blumbergs PC, Gai WP. NSF, 361 Reynolds PN, Hodge S. The impact of defective clearance of apoptotic Unc-18-1, dynamin-1 and HSP90 are inclusion body components in cells in the pathogenesis of chronic lung diseases: chronic obstructive neuronal intranuclear inclusion disease identified by anti-SUMO-1- pulmonary disease, asthma and cystic fibrosis. In: Phagocytosis of immunocapture. Acta Neuropathologica 116:603-614, 2008. Dying Cells: From molecular Mechanisms to Human Diseases. 343 Power JHT, Asad S, Chataway TK, Chegini F, Manavis J, Temlett JA, Editors: Krysko DV, Vandenabeele P, Springer Publisher 2008. Jensen PH, Blumbergs PC, Gai WP. Peroxiredoxin 6 in human brain: 362 Ricciardelli C, Jackson MW, Choong CS, Stahl J, Marshall VR, molecular forms, cellular distribution and association with Alzheimer’s Horsfall DJ, Tilley WD. Elevated levels of HER-2/neu and androgen disease pathology. Acta Neuropathologica 115:611-622, 2008. receptor in clinically localized prostate cancer identifies metastatic 344 Prabhakaran VC, Bhatnagar A, Sandilla J, Olver J, Leibovitch I, potential. Prostate 68(8):830-838, 2008. Ghabrial R, Goldberg RA, Selva D. Orbital and adnexal rosai-dorfman 363 Roberts-Thomson KC, Stevenson IH, Kistler PM, Haqqani HM, disease. Orbit 27:356-362, 2008. Goldblatt JC, Sanders P, Kalman JM. Anatomically determined 345 Prabhakaran VC, Crompton J, Singhall N, Madge SN, Selva D. functional conduction delay in the posterior left atrium relationship to Perineural involvement of the frontal nerve by benign lymphoid structural heart disease. Journal of the American College of hyperplasia. Clinical & Experimental Ophthalmology 36:481-483, Cardiology 51:856-862, 2008. 2008. 364 Rogers NM, Coates PT. Calcific uraemic arteriolopathy: an update. 346 Prabhakaran VC, Davis G, Wormald PJ, Selva D. Congenital absence Current Opinion in Nephrology & Hypertension 17:629-634, 2008. of the nasolacrimal duct in velocardiofacial syndrome. J AAPOS 365 Rogers NM, Peh CA, Faull R, Pannell M, Cooper J, Russ GR. 12:85-86, 2008. Transmission of toxoplasmosis in two renal allograft recipients 347 Prabhakaran VC, Selva D. Orbital endoscopic surgery. Indian Journal receiving an organ from the same donor. Transplant Infectious Disease of Ophthalmology 56:5-8, 2008. 10:71-74, 2008. 348 Proudman SM, Cleland LG, James MJ. Dietary omega-3 fats for 366 Ross DM, Hughes TP. Current and emerging tests for the laboratory treatment of inflammatory joint disease: efficacy and utility. Rheumatic monitoring of chronic myeloid leukaemia and related disorders. Diseases Clinics of North America 34:469-479, 2008. Pathology 40:231-246, 2008. 349 Psaltis PJ, Carbone A, Nelson A, Lau DH, Manavis J, Finnie J, Teo KS, 367 Ross DM, Hughes TP. How complete is “complete” molecular Mackenzie L, Sanders P, Gronthos S, Zannettino AC, Worthley SG. response in imatinib-treated chronic myeloid leukemia? Leukemia An ovine model of toxic, nonischemic cardiomyopathy-assessment & Lymphoma 49:1230-1231, 2008. by cardiac magnetic resonance imaging. Journal of Cardiac Failure 368 Ross DM, Watkins DB, Hughes TP, Branford S. Reverse transcription 14:785-795, 2008. with random pentadecamer primers improves the detection limit of a 350 Psaltis PJ, Dundon BK, Teo KS, Worthley SG. Utility of cardiac quantitative PCR assay for BCR-ABL transcripts in chronic myeloid magnetic resonance imaging in detection of post-infarction intra- leukemia: Implications for defining sensitivity in minimal residual myocardial dissection. Heart Lung & Circulation 17:415-416, 2008. disease. Clinical Chemistry 54:1568-1571, 2008. 351 Psaltis PJ, Gronthos S, Worthley SG, Zannettino ACW. Cellular therapy 369 Ross IL, Heuzenroeder MW. A comparison of three molecular typing for cardiovascular disease, part 1 – Preclinical insights. Clinical methods for the discrimination of Salmonella enterica serovar Infantis. Medicine: Cardiology 2:125-138, 2008. FEMS Immunology and Medical Microbiology 53:375-384, 2008. 352 Psaltis PJ, Gronthos S, Worthley SG, Zannettino ACW. Cellular therapy 370 Royle PJ, McIntosh GH, Clifton PM. Whey protein isolate and for cardiovascular disease part 2 – Delivery of cells and clinical glycomacropeptide decrease weight gain and alter body composition experience. Clinical Medicine: Cardiology 2:139-151, 2008. in male Wistar rats. British Journal of Nutrition 100:88-93, 2008. 353 Psaltis PJ, Zannettino A, Worthley SG, Gronthos S. Mesenchymal 371 Ruan Y, Foo TC, Warren-Smith S, Hoffmann P, Moore RC, Ebendorff stromal cells - potential for cardiovascular repair. Stem Cells 26:2201- Heidepriem H, Monro TM. Antibody immobilization within glass 2210, 2008. microstructured fibers: a route to sensitive and selective biosensors. Optics Express 16:18514-18523, 2008.

58 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

372 Rudkin AK, Edussuriya K, Sennanayake S, Senaratne T, Selva D, 387 Shukri MJ, Watson DI, Lally CJ, Devitt PG, Jamieson GG. Sullivan T, Casson RJ. Prevalence of exfoliation syndrome in central Laparoscopic anterior 90 degree fundoplication for reflux or large Sri Lanka: the Kandy Eye Study. British Journal of Ophthalmology hiatus hernia. ANZ Journal of Surgery 78:123-127, 2008. 92:1595-1598, 2008. 388 Simon S, Selva D, Crompton JL. Torsten Nils Weisel. Clinical & 373 Rumbold AR, Cunningham J, Bailie RS, Hiller JE. Exploring the Experimental Ophthalmology 36:185, 2008. characteristics of the research workforce in Aboriginal and Torres Strait 389 Singh P, Smith CL, Cheetham G, Dodd TJ, Davy ML. Serous Islander health. Australian and New Zealand Journal of Public Health carcinoma of the uterus-determination of HER-2/neu status using 32:12-18, 2008. immunohistochemistry, chromogenic in situ hybridization, and 374 Saggu SK, Chotaliya HP, Cai Z, Blumbergs P, Casson RJ. The quantitative polymerase chain reaction techniques: its significance and spatiotemporal pattern of somal and axonal pathology after perikaryal clinical correlation. International Journal of Gynaecological Cancer excitotoxic injury to retinal ganglion cells: A histological and 18:1344-1351, 2008. morphometric study. Experimental Neurology 211:52-58, 2008. 390 Singhal N, Hissaria P, Joshi R, Nayagam S. Inflammatory myopathy 375 Sakko AJ, Butler MS, Byers S, Reinboth BJ, Stahl J, Kench JG, and cancer: rare association of seminoma testes and polymyositis. Horvath LG, Sutherland RL, Stricker PD, Henshall SM, Marshall VR, Internal Medicine Journal 38:295-297, 2008. Tilley WD, Horsfall DJ, Ricciardelli C. Immunohistochemical level of 391 Sipe W, Brierley SM, Martin CM, Phillis BD, Bautista Cruz F, Grady EF, unsulfated chondroitin disaccharides in the cancer stroma is an Liedtke W, Cohen DM, Vanner SJ, Blackshaw LA, Bunnett NW. independent predictor of prostate cancer relapse. Cancer Transient receptor potential vanilloid 4 mediates protease activated Epidemiology Biomarkers and Prevention 17:2488-2497, 2008. receptor 2-induced sensitization of colonic afferent nerves and visceral 376 Sanders P, Hocini M, Jaïs P, Takahashi Y, Rostock T, Sacher F, Jonsson hyperalgesia. American Journal of Physiology. Gastrointestinal and A, Rotter M, Hsu LF, Haïssaguerre M. Pulmonary and thoracic vein Liver Physiology 294:G1288-1298, 2008. sources: the focal theory of atrial fibrillation. In: Manual of Surgical 392 Smith B, Chur-Hansen A, Neale A, Symon J. Quality of life and Treatment of Atrial Fibrillation, Sie H, D’Ancona G, Bartolozzi F, cholinesterase inhibitors: a qualitative study of patients with Beukema W, Doty D, editors, Blackwell Publishing Limited, Oxford, Alzheimer’s Disease and their carers. Australasian Psychiatry 16:433- United Kingdom, Part I, Chapter 6, 2008. 437, 2008. 377 Savilla K, Kettler L, Galletly C. Relationships between cognitive 393 Smith DP, Supramaniam R, Marshall VR, Armstrong BK. Prostate deficits, symptoms and quality of life in schizophrenia. Australian and cancer and prostate-specific antigen testing in New South Wales. New Zealand Journal of Psychiatry 42:496-504, 2008. Medical Journal of Australia 189:315-318, 2008. 378 Schaller CE, Wang CL, Beck-Engeser G, Goss L, Scott HS, Anderson 394 Smith E, De Young NJ, Pavey SJ, Hayward NK, Nancarrow DJ, MS, Wabl M. Expression of Aire and the early wave of apoptosis in Whiteman DC, Smithers BM, Ruszkiewicz AR, Clouston AD, Gotley spermatogenesis. Journal of Immunology Feb 1;180:1338-1343, 2008. DC, Devitt PG, Jamieson GG, Drew PA. Similarity of aberrant DNA 379 Schloithe AC, Sutherland K, Woods CM, Blackshaw LA, Davison JS, methylation in Barrett’s esophagus and esophageal adenocarcinoma. Toouli J, Saccone GT. A novel preparation to study rat pancreatic Molecular Cancer 7:75, 2008. spinal and vagal mechanosensitive afferents in vitro. 395 Smith E, De Young NJ, Tian ZQ, Caruso M, Ruszkiewicz AR, Liu JF, Neurogastroenterology & Motility 20:1060-1069, 2008. Jamieson GG, Drew PA. Methylation of TIMP3 in esophageal 380 Schober MS, Chidlow G, Wood JP, Casson RJ. Bioenergetic-based squamous cell carcinoma. World Journal of Gastroenterology 14:203- neuroprotection and glaucoma. Clinical & Experimental 210, 2008. Ophthalmology 36:377-385, 2008. 396 Smith IM, Harvey N, Logan RM, David DJ, Anderson PJ. Odontogenic 381 Schuetz F, Kumar S, Poronnik P, Adams DJ. Regulation of the voltage keratocyst in a 5-year-old child: a rare cause of maxillary swelling in gated K+ channels KCNQ2/3 and 3/5 by serum and glucocorticoid- children. Journal of Plastic Reconstructive and Aesthetic Surgery regulated kinase-1. American Journal of Physiology. Cell Physiology 61:189-191, 2008. 295:C73-80, 2008. 397 Smith JA, Braunack-Mayer A, Wittert G, Warin M. “It’s sort of like 382 Seach N, Ueno T, Fletcher AL, Lowen T, Mattesich M, Engwerda CR, being a detective”: Understanding how Australian men self-monitor Scott HS, Ware CF, Chidgey AP, Gray DH, Boyd RL. The lymphotoxin their health prior to seeking help. BMC Health Services Research 8:56, pathway regulates Aire-independent expression of ectopic genes and 2008. chemokines in thymic stromal cells. Journal of Immunology 398 Smith JA, Braunack-Mayer AJ, Wittert GA, Warin MJ. Qualities men 180:5384-5392, 2008. value when communicating with general practitioners: implications for 383 Severi G, Hayes VM, Tesoriero AA, Southey MC, Hoang HN, Padilla primary care settings. Medical Journal of Australia 189:618-621, EJ, Morris HA, English DR, Sutherland RL, Boyle P, Hopper JL, Giles 2008. GG. The rs743572 common variant in the promoter of CYP17A1 is not 399 Smith LJ, Byers S, Costi J, Fazzalari NL. Elastic fibers enhance the associated with prostate cancer risk or circulating hormonal levels. mechanical integrity of the human lumbar anulus fibrosus in the radial BJU International 2007 101:492-496, 2008. direction. Annals of Biomedical Engineering 36:214-223, 2008. 384 Shah NP, Kantarjian HM, Kim DW, Réa D, Dorlhiac-Llacer PE, Milone 400 Solomon LB, Pohl AP, Chehade MJ, Malcolm AM, Howie DW, JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Henneberg M. Surgical anatomy for pelvic external fixation. Clinical Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Anatomy 21:674-682, 2008. Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with 401 Solomon LB, Stevenson AW. Tibial insertion of the biceps femoris Dasatinib 100 mg once daily preserves efficacy and improves tendon: anatomical and radiological description of an anatomical tolerability in Imatinib-resistant and -intolerant chronic-phase chronic variant. Clinical Anatomy 21:802-804, 2008. myeloid leukemia. Journal of Clinical Oncology 26:3204-3212, 2008. 402 Somogyi AA, Larsen M, Abadi RM, Jittiwutikarn J, Ali R, White JM. 385 Shaw M, Dent J, Beebe T, Junghard O, Wiklund I, Lind T, Johnsson F. Flexible dosing of Tincture of Opium in the management of opioid The reflux disease questionnaire: a measure for assessing treatment withdrawal: pharmacokinetics and pharmacodynamics. British Journal response in clinical trials. Health & Quality of Life Outcomes 6:31, of Clinical Pharmacology 66:640-647, 2008. 2008. 386 Shimamura Y, Holding C, Haynes DR, Vernon-Roberts B, Blumbergs PC, Fraser RD, Moore RJ. The biologic response to particles from a potential disc prosthesis material. Spine 33:351-355, 2008.

59 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

403 Sonneveld P, Hajek R, Nagler A, Spencer A, Bladé J, Robak T, Zhuang 419 Summers BL, Henry CM, Rofe AM, Coyle P. Dietary zinc SH, Harousseau JL, Orlowski RZ; for the DOXIL-MMY-3001 Study supplementation during pregnancy prevents spatial and object Investigators in addition to the authors, Horvath N (Adelaide), amongst recognition memory impairments caused by early prenatal ethanol many others. Combined pegylated liposomal doxorubicin and exposure. Behavioural Brain Research 186:230-238, 2008. bortezomib is highly effective in patients with recurrent or refractory 420 Sutton-Smith P, Beard H, Fazzalari N. Quantitative backscattered multiple myeloma who received prior thalidomide/lenalidomide electron imaging of bone in proximal femur fragility fracture and therapy. Cancer 112:1529-1537, 2008. medical illness. Journal of Microscopy 229:60-66, 2008. 404 Sorich MJ, Smith PA, Miners JO, Mackenzie PI, McKinnon RA. Recent 421 Sykes MJ, McKinnon RA, Miners JO. Prediction of metabolism by advances in the in silico modelling of UDP glucuronosyltransferase cytochrome P450 2C9: Alignment and docking studies of a validated substrates. Current Drug Metabolism 9:60-69, 2008. database of substrates. Journal of Medicinal Chemistry 51:780-791, 405 Southwood M, Jeffery T, Yang X, Upton P, Hall S, Atkinson C, Haworth 2008. S, Stewart S, Reynolds P, Long L, Trembath R, Morrell N. Regulation of 422 Tai K, Need AG, Horowitz M, Chapman IM. Glucose tolerance and bone morphogenetic protein signalling in human pulmonary vascular vitamin D: Effects of treating vitamin D deficiency. Nutrition 24:950- development. Journal of Pathology 214:85-95, 2008. 956, 2008. 406 Sowman PF, Thompson PD, Miles TS. Investigation of an unusual, 423 Tai K, Need AG, Horowitz M, Chapman IM. Vitamin D, glucose, high-frequency jaw tremor with coherence analysis. Movement insulin, and insulin sensitivity. Nutrition 24:279-285, 2008. Disorders 23:441-443, 2008. 424 Tak PP, Thurlings RM, Rossier C, Nestorov I, Dimic A, Mircetic V, 407 Sriram K, Jersmann H. Pneumothorax, pneumomediastinum and Rischmueller M, Nasonov E, Shmidt E, Emery P, Munafo A. Atacicept subcutaneous emphysema following closed percutaneous pleural in patients with rheumatoid arthritis: Results of a multicenter, phase ib, biopsy: a case report. Cases Journal 1:274, 2008. double-blind, placebo-controlled, dose-escalating, single- and 408 Sriram K, Moffatt D, Stapledon R. Tuberculosis infection of the breast repeated-dose study. Arthritis & Rheumatism 58:61-72, 2008. mistaken for granulomatous mastitis: a case report. Cases Journal 425 Takahashi Y, O’Neill MD, Hocini M, Dubois R, Matsuo S, Knecht S, 1:273, 2008. Mahapatra S, Lim KT, Jaïs P, Jonsson A, Sacher F, Sanders P, Rostock 409 Sriram K, Robinson P. Recurrent airway obstructions in a patient with T, Bordachar P, Clémenty J, Klein GJ, Haïssaguerre M. Characterization benign tracheal stenosis and a silicone airway stent: a case report. of electrograms associated with termination of chronic atrial fibrillation Cases Journal 1:226, 2008. by catheter ablation. Journal of the American College of Cardiology 410 Sriram KB, Thornton A, Antic R. Spontaneous mode non-invasive 51:1003-1010, 2008. ventilation fails to treat respiratory failure in a patient with Multi- 426 Tay J, Brinkworth GD, Noakes M, Keogh J, Clifton PM. Metabolic mincore disease: a case report. Cases Journal 1:93, 2008. effects of weight loss on a very-low-carbohydrate diet compared with 411 Stevens JE, Russo A, Maddox AF, Rayner CK, Phillips L, Talley NJ, an isocaloric high-carbohydrate diet in abdominally obese subjects. Giguère M, Horowitz M, Jones KL. Effect of itopride on gastric Journal of the American College of Cardiology 51:59-67, 2008. emptying in longstanding diabetes mellitus. Neurogastroenterology 427 Teo KS, Carbone A, Piantadosi C, Chew DP, Hammett CJ, Brown MA, & Motility 20:456-463, 2008. Worthley SG. Cardiac MRI assessment of left and right ventricular 412 Stiles MK, Brooks AG, John B; Shashidhar, Wilson L, Kuklik P, Dimitri parameters in healthy Australian normal volunteers. Heart, Lung & H, Lau DH, Roberts-Thomson RL, Mackenzie L, Willoughby S, Young Circulation 17:313-317, 2008. GD, Sanders P. The effect of electrogram duration on quantification of 428 Tewari N, Gill PG, Bochner MA, Kollias J. Comparison of volume complex fractionated atrial electrograms and dominant frequency. displacement versus circumferential arm measurements for Journal of Cardiovascular Electrophysiology 19:252-258, 2008. lymphoedema: implications for the SNAC trial. ANZ Journal of 413 Stiles MK, Brooks AG, Kuklik P, John B, Dimitri H, Lau DH, Wilson L, Surgery 78:889-893, 2008. Dhar S, Roberts-Thomson RL, Mackenzie L, Young GD, Sanders P. 429 Tewari N, Gill PG, Bochner MA, Kollias J. Comparison of volume High-density mapping of atrial fibrillation in humans: Relationship displacement versus circumferential arm measurements for between high-frequency activation and electrogram fractionation. lymphoedema: implications for the SNAC trial. ANZ Journal of Journal of Cardiovascular Electrophysiology 19:1245-53, 2008. Surgery 78:889-893, 2008. 414 Stiles MK, Brooks AG, Sanders P. Putting CFAE on the map. Journal 430 Thomas SD, Need AG, Tucker G, Slobodian P, O’Loughlin PD, Nordin of Cardiovascular Electrophysiology 19:904-906, 2008. BE. Suppression of parathyroid hormone and bone resorption by 415 Stiles MK, Dabbous OH, Fox KA; on behalf of the GRACE calcium carbonate and calcium citrate in postmenopausal women. investigators. Bleeding events with antithrombotic therapy in patients Calcified Tissue International 83:81-84, 2008. with unstable angina or non-ST-segment elevation myocardial 431 Thompson PD. Unravelling the tortuous tale of dystonia. Book Review. infarction; insights from a large clinical practice registry (GRACE). Lancet Neurology 7:480, 2008 Heart, Lung & Circulation 17:5-8, 2008. 432 Thompson PD. Gait disorders. In: Neurology in Clinical Practice, Fifth 416 Street JM, Braunack-Mayer AJ, Facey K, Ashcroft RE, Hiller JE. Virtual Edition. Bradley WG, Daroff RB, Fenichel GM, Jankovic J, editors. community consultation? Using the literature and weblogs to link Butterworth-Heinemann (Elsevier) Chapter 24, pp327-338, 2008. community perspectives and health technology assessment. 433 Thompson PD. Muscle cramp syndromes. In: Handbook of Clinical Health Expectations 11:189-200, 2008. Neurology, Volume 86 (3rd series) Myopathies. Mastaglia FL, Hilton 417 Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Keefe DM. Jones D, editors. Elsevier, Chapter 19, pp389-396, 2008. Faecal microflora and beta-glucuronidase expression are altered in an 434 Thompson PD, Meinck H-M. Stiff Person syndrome. In: Therapeutics irinotecan-induced diarrhoea model in rats. Cancer Biology & Therapy of Parkinson’s Disease and Movement Disorders, Hallett M, Poewe W, 7:1919-1925, 2008. editors, Wiley Blackwell Chapter 18, pp283-291 2008. 418 Strother RM, Sweeney C. Lessons learned from development of 435 Thompson SK, Ruszkiewicz AR, Jamieson GG, Esterman A, Watson DI, docetaxel. Expert Opinion on Drug Metabolism & Toxicology 4:1007- Wijnhoven BP, Lamb PJ, Devitt PG. Improving the accuracy of TNM 1019, 2008. staging in esophageal cancer: A pathological review of resected specimens. Annals of Surgical Oncology 15:3447-3458, 2008.

60 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

436 Thomson RL, Buckley JD, Noakes M, Clifton PM, Norman RJ, 452 Verrall GM, Henry L, Fazzalari NL, Slavotinek JP, Oakeshott RD. Bone Brinkworth GD. The effect of a hypocaloric diet with and without biopsy of the parasymphyseal pubic bone region in athletes with exercise training on body composition, cardiometabolic risk profile, chronic groin injury demonstrates new woven bone formation and reproductive function in overweight and obese women with consistent with a diagnosis of pubic bone stress injury. American polycystic ovary syndrome. Journal of Clinical Endocrinology Journal of Sports Medicine 36:2425-2431, 2008. & Metabolism 93:3373-3380, 2008. 453 Ward MB, Kotasek D, McKinnon RA. Investigation of HTR3C mutations 437 Trevisin M, Pollock W, Dimech W, Melny J, Paspaliaris B, Gillis D, for association with 5HT(3) receptor antagonist anti-emetic efficacy. Wong R, Savige J. Antigen-specific ANCA ELISAs have different Pharmacogenomics 9:1027-1033, 2008. sensitivities for active and treated vasculitis and for nonvasculitic 454 Warrier S, Prabhakaran VC, Davis G, Selva D. Delayed complications disease. American Journal of Clinical Pathology 129:42-53, 2008. of silicone implants used in orbital fracture repairs. Orbit 27:147-151, 438 Tsopelas C, Adam B, Liebregts T, Holtmann G, Bartholomeusz FD. 2008. Colonic transit studies with 99mTc-rhenium sulfide colloid in live rats. 455 Warrier S, Prabhakaran VC, Valenzuela A, Sullivan TJ, Davis G, Selva A preliminary study. Hellenic Journal of Nuclear Medicine 11:96-100, D. Orbital arteriovenous malformations. Archives of Ophthalmology 2008. 126:1669-1675, 2008. 439 Tsopelas C, Bellon M, Bevington E, Kollias J, Shibli S, Chatterton BE. 456 Warrier SK, Jain R, Gilhotra JS, Newland HS. Sutureless vitrectomy. Lymphatic mapping with (99m)Tc-Evans Blue dye in sheep. Annals of Indian Journal of Ophthalmology 56:453-458, 2008. Nuclear Medicine 22:777-785, 2008. 457 Warrier SK, Wu HM, Newland HS, Muecke JS, Selva D, Aung T, 440 Tuckwell W, Bezak E, Yeoh E, Marcu L. Efficient Monte Carlo modelling Casson RJ. Ocular biometry and determinants of refractive error in of individual tumour cell propagation for hypoxic head and neck rural Myanmar: The Meiktila Eye Study. British Journal of cancer. Physics in Medicine & Biology 53:4489-4507, 2008. Ophthalmology 92:1591-1594, 2008. 441 Tully PJ, Baker RA, Turnbull D, Winefield H. The role of depression 458 Warrilow D, Meredith L, Davis A, Burrell C, Li P, Harrich D. Cell and anxiety symptoms in hospital readmissions after cardiac surgery. factors stimulate HIV-1 reverse transcription in vitro. Journal of Journal of Behavioural Medicine 31:281-290, 2008. Virology 82:1425-1437, 2008. 442 Tumes DJ, Wong AC, Sewell WA, McColl SR, Connolly A, Dent LA. 459 Welldon KJ, Atkins GJ, Howie DW, Findlay DM. Primary human Differential rates of apoptosis and recruitment limit eosinophil osteoblasts grow into porous tantalum and maintain an osteoblastic accumulation in the lungs of asthma-resistant CBA/Ca mice. phenotype. Journal of Biomedical Materials Research A 84:691-701, Molecular Immunology 45:3609-3617, 2008. 2008. 443 Tytgat GN, McColl K, Tack J, Holtmann G, Hunt RH, Malfertheiner P, 460 White AJ, Withers DR, Parnell SM, Scott HS, Finke D, Lane PJ, Hungin AP, Batchelor HK. New algorithm for the treatment of Jenkinson EJ, Anderson G. Sequential phases in the development of gastroesophageal reflux disease. Alimentary Pharmacology and Aire-expressing medullary thymic epithelial cells involve distinct Therapeutics 27:249-256, 2008. cellular input. European Journal of Immunology 38:942-947, 2008. 444 Upton RN, Martinez AM, Grant C. A dose escalation study in sheep of 461 White DL. Is telomerase a player in chronic phase chronic myeloid the effects of the benzodiazepine CNS 7056 on sedation, the EEG and leukemia, disease progression and imatinib resistance? Leukemia & the respiratory and cardiovascular systems. British Journal of Lymphoma 49:1022-1023, 2008. Pharmacology 155:52-61, 2008. 462 Williams LM, Whitford TJ, Flynn G, Wong W, Liddell BJ, Silverstein S, 445 Upton RN, Rasmussen M, Grant C, Martinez AM, Cold GE, Ludbrook Galletly C, Harris AW, Gordon E. General and social cognition in first GL. Pharmacokinetics and pharmacodynamics of indomethacin: effects episode schizophrenia: Identification of separable factors and on cerebral blood flow in anaesthetized sheep. Clinical & Experimental prediction of functional outcome using the IntegNeuro test battery. Pharmacology & Physiology 35:317-323, 2008. Schizophrenia Research 99:182-191, 2008. 446 Upton RN. Organ weights and blood flows of sheep and pig for 463 Windsor JA, Sturm LP, Cosman PH, Cregan P, Hewett PJ, Maddern GJ. physiological pharmacokinetic modelling. Journal of Pharmacological A systematic review of skills transfer after surgical simulation training. & Toxicological Methods 58:198-205, 2008. Annals of Surgery 248:691, 2008. 447 van Orshoven NP, van Schelven LJ, Akkermans LM, Jansen PA, 464 Winefield HR, Black A, Chur-Hansen A. Health effects of ownership of Horowitz M, Feinle-Bisset C, van Huffelen AC, Oey PL. The effect of and attachment to companion animals in an older population. intraduodenal glucose on muscle sympathetic nerve activity in healthy International Journal of Behavioral Medicine 15:303-310, 2008. young and older subjects. Clinical Autonomic Research 18:28-35, 465 Wong AS, Myers JC, Jamieson GG. Esophageal pH profile following 2008. laparoscopic total fundoplication compared to anterior fundoplication. 448 Vanlint S, Nugent M, Durvasula S, Downs J, Leonard H. A guide for Journal of Gastrointestinal Surgery 12:1341-1345, 2008. the assessment and management of vitamin D status in people with 466 Wong MX, Hayball JD, Jackson DE. PECAM-1-regulated signalling intellectual disability (developed as an AADDM Working Party thresholds control tolerance in anergic transgenic B-cells. Molecular initiative). Journal of Intellectual Development & Disability 33:184- Immunology 45:1767-1781, 2008. 188, 2008. 467 Wong RC, Favaloro EJ, Adelstein S, Baumgart K, Bird R, Brighton TA, 449 Vanlint S, Nugent M, Durvasula S. Vitamin D and people with Empson M, Gillis D, Hendle MJ, Laurent R, Mallon D, Pollock W, intellectual disability. Australian Family Physician 37:348-350, 2008. Smith S, Steele RH, Wilson RJ. Consensus guidelines on anti-beta 2 450 Verhoef L, Depoortere E, Boxman I, Duizer E, van Duynhoven Y, Harris glycoprotein I testing and reporting. Pathology 40:58-63, 2008. J, Johnsen C, Kroneman A, Le Guyader S, Lim W, Maunula L, Meldal 468 Wood JP, Lascaratos G, Bron AJ, Osborne NN. The influence of visible H, Ratcliff R, Reuter G, Schreier E, Siebenga J, Vainio K, Varela C, light exposure on cultured RGC-5 cells. Molecular Vision 14:334-44, Vennema H, Koopmans M. Emergence of new norovirus variants on 2008. spring cruise ships and prediction of winter epidemics. Emerging Infectious Diseases 14:238-243, 2008. 469 Worthley SG, Reis ED, Helft G, Worthley MI, Fayad ZA. Serial magnetic resonance imaging correlates with neurological outcome in an 451 Vernon-Roberts B, Moore RJ, Fraser RD. The natural history of age experimental model of spinal cord ischemia. Spinal Cord 46:222-227, related disc degeneration: the influence of age and pathology on cell 2008. populations in the L4-L5 disc. Spine 33:2767-2773, 2008.

61 Annual Report 2008 Hanson Institute Proudly bringing together the best PUBLICATIONS of South Australia’s medical research

470 Wu HM, Casson RJ, Newland HS, Muecke J, Selva D, Aung T. 488 Zhang Y, Bi P, Hiller J. Climate variations and salmonellosis Anisometropia in an adult population in rural myanmar: the Meiktila transmission in Adelaide, South Australia: a comparison between Eye Study. Ophthalmic Epidemiology 15:162-166, 2008. regression models. International Journal of Biometeorology 52:179- 471 Wu KL, Rayner CK, Chuah SK, Changchien CS, Lu SN, Chiu YC, Chiu 187, 2008. KW, Lee CM. Effects of ginger on gastric emptying and motility in 489 Zhang Y, Bi P, Hiller JE. Climate Change and Population Health. In: healthy humans. European Journal of Gastroenterology & Hepatology Climate Change Research Progress, Peretz LN ed, New York, Nova 20:436-440, 2008. Sciences Publishers Inc 2008. 472 Wyatt L, Khew-Goodall Y. PTP-Pez: A novel regulator of TGFbeta 490 Zhang Y, Bi P, Hiller JE. Weather and the transmission of bacillary signaling. Cell Cycle 7:2290-2295, 2008. dysentery in Jinan, northern China: a time-series analysis. Public 473 Wycherley TP, Brinkworth GD, Noakes M, Buckley JD, Clifton PM. Health Reports 123:61-66, 2008. Effect of caloric restriction with and without exercise training on 491 Zschau N, Nguyen N, Tam W, Schoeman M. Intestinal perforation: a oxidative stress and endothelial function in obese subjects with type 2 rare complication of percutaneous endoscopic jejunostomy removal. diabetes. Diabetes, Obesity & Metabolism 10:1062-1073, 2008. Endoscopy 40 Suppl 2:E178, 2008. 474 Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S, Le A, Wang CY, Chen W, Shi S. Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS ONE 3:e2615, 2008. 475 Yates PJ, Quraishi NA, Kop A, Howie DW, Marx C, Swarts E. Fractures of modern high nitrogen stainless steel cemented stems cause, mechanism, and avoidance in 14 cases. Journal of Arthroplasty 23:188-196, 2008. 476 Yelland LN, Burns JP, Sims DN, Salter AB, White JM. Inter- and intra subject variability in ethanol pharmacokinetic parameters: Effects of testing interval and dose. Forensic Science International 175:65-72, 2008. 477 Yeoh E. Radiotherapy: long-term effects on gastrointestinal function. Current Opinion in Supportive and Palliative Care 2:40-44, 2008. 478 Ying Zhang, Peng Bi, Hiller JE. Climate change and the transmission of vector-borne diseases: a review. Asia Pacific Journal of Public Health 20:64-76, 2008. 479 Yong TY, Li JY, Amato L, Mahadevan K, Phillips PJ, Coates PS, Coates PT. Pituitary involvement in Wegener’s granulomatosis. Pituitary 11:77-84, 2008. 480 Young RL, Cooper NJ, Blackshaw LA. Anatomy and function of group III metabotropic glutamate receptors in ferret gastric vagal pathways. Neuropharmacology 54:965-975, 2008. 481 Young RL, Cooper NJ, Blackshaw LA. Chemical coding and central projections of gastric vagal afferent neurons. Neurogastroenterology & Motility 20:708-718, 2008. 482 Yu C, Moghaddami M, Mayrhofer G. Expression of a B-cell-restricted isoform of CD45 is associated with maturity in rat serosal and connective-tissue mast cells. Immunology 125:558-569, 2008. 483 Zannettino AC, Paton S, Arthur A, Khor F, Itescu S, Gimble JM, Gronthos S. Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. Journal of Cellular Physiology 214:413-421, 2008. 484 Zannettino AC, Psaltis PJ, Gronthos S. Home is where the heart is: via the FROUNT. Cell Stem Cell 2:513-514, 2008. 485 Zannettino ACW. Bone Loss, Cancer Mediated. Encyclopedia of Cancer, Second Edition, Ed. Schwab M, Springer Publishers, pgs 382- 385, 2008. 486 Zhang D, Bi P, Hiller JE, Lv F. Web-based HIV/AIDS behavioral surveillance among men who have sex with men: potential and challenges. International Journal of Infectious Diseases 12:126-131, 2008. 487 Zhang D, Bi P, Lv F, Zhang J, Hiller JE. Differences between Internet and community samples of MSM: implications for behavioral surveillance among MSM in China. AIDS Care 20:1128-1137, 2008.

62 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH GRANTS COMMENCING 2009 of South Australia’s medical research

Alcohol and Health Research Grants Scheme Hanson Institute NHMRC Project Grants Coyle P Alcohol & Health Grant Scheme: The effect of dietary zinc supplement throughout pregnancy on alcohol mediated changes in the Number of Grants expression of neurodevelopment genes 0 5101520253035402009 $35,000 Amgen Inc. *08 $20,684,825 Townsend A, Hardingham J, Price T Phase II study of second line therapy with irinotecan, panitumumab, and everolimus in metastatic 07 $16,297,355 colorectal cancer with KRAS wild-type. 2009 – 2010 $160,000 06 Amgen Australia Pty Ltd $12,167,801 Fazzalari N PhD Scholarship grant for a student to undertake PhD studies 05 to assist Professor Fazzalari with the elucidation of the contribution of $8,179,700 structural and material factors to the risk of fragility femoral fractures 2009 $35,000 04 $3,064,925 Arthritis Australia

0 5 10 15 20 25 Briggs AM, Parkinson IH, Fazzalari NL, Wark JD Subregional bone mineral density in the lumbar spine: Improving osteoporosis assessment Total value of Grants ($M) 2009 $10,000 Hissaria P, Khew-Goodall Y, Proudman S Identification of novel Number of NHMRC Project Grants awarded markers and molecular targets in pathological fibrosis in scleroderma skin Total value of NHMRC Project Grants ($M) lesions 2009 $45,000 Grants won for the period and commencing the following year. Excludes external members and fellowships Australian Academy of Science *Includes SA Pathology researchers at WCH and FMC. Oehler MK, Hoffmann P, Ricciardelli C, Brown MP Scientific Visits to Europe Award: Novel in vivo targeting of dead tumour cells exerts potent Funding of research mainly comes from external agencies that bystander killing effects allocate their funds on a competitive basis following national and 2009 $5,300 international peer-review of applications. The major medical Australian and New Zealand Society of Nuclear Medicine research funding agency in Australia is the National Health and Smyth D, Al-Ejeh F, Tsopelas C, Brown MP, Chatterton B Research Medical Research Council (NHMRC), funded by the Federal Grant: Molecular imaging with gallium-68 labelled biomolecules Government’s Department of Health and Ageing. The NHMRC 2009 $19,860 awarded funding totalling $23.5 million to Hanson Institute Australian Cancer Research Foundation researchers for research to commence in 2009. This is the largest amount of NHMRC funding awarded to Hanson Institute Lindeman G, Strasser A, Alexander W, Ernst M, Forrest S, Gibbs researchers since its inauguration in 2001. This increase P, Hibbs M, Hilton D, Huang D, Mann B, Roberts A, Scott H, includes the contribution by SA Pathology researchers. This Speed T, Stacker S, Visvader J ACRF Centre for Therapeutic outstanding achievement is a fitting testament to the high quality Target Discovery research conducted at the Hanson Institute and places it as one 2009 $5,000,000 of the finest medical research institutes in Australia. NHMRC Australian Dental Research Foundation project grants are usually funded over a three year period. Zilm P, Hoffmann P The use of MALDI mass spectrometry and biotyper Other agencies such as The Cancer Council South Australia raise software to identify oral bacteria money from donations by the general public and allocate their 2009 $6,000 funds to research projects on a similar basis. Each and every source of income is essential for the continued work of the Australian Lung Foundation Hanson Institute and success with applications is an indication Reynolds P Slater & Gordon Asbestos Research Fund: Optimisation of of the scientific excellence. immune-viral therapy for mesothelioma 2009 $30,000 Key: Australian Research Council Funding Body Barry SC, Zola H, D’Andrea RJ, Lewis I Collaborating/Partner Investigators Organisations: Women’s & Children’s Health Research Institute and Title of Grant Cellsense Pty Ltd Linkage Project: Differentiation of cord blood stem cells Period of Grant, Amount PA (A$) into thymus (T) cells with regulatory phenotype and function 2009 – 2011 $100,000 Bowie JH, Ball A, Brooks DA, Buntine MA, Chataway T, Hoffmann P, Lawrance WD, Lopez AF, McColl SR, Miners JO, Voelcker NH with partner organisations and collaborating organisations: The University of Adelaide, The Flinders University of South Australia, University of South Australia, Hanson Institute (IMVS), CSIRO Health Flagship LIEF grant: South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility 2009 $400,000

63 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH GRANTS COMMENCING 2009 of South Australia’s medical research

Hugo GJ, Wittert GA, Adams RJ, Cobiac L, Daniel M, Findlay CC, Reynolds PN, Holmes M Virus and immune therapy for mesothelioma Taylor AW, Wilson DH, Winefield HR, Woollacott AL, Ruffin R 2009 $89,750 with collaborating/partner organisations: Queen Elizabeth Scott H, D’Andrea R, Suthers G, Bardy P, Hughes T, Lewis I, Hospital Research Foundation, Workcover SA, Council on the Mullighan C, Hahn C Familial blood cancers Ageing, SA Health Linkage Project: Australia’s baby boomer generation, 2009 $101,500 obesity and work – patterns, causes and implications Sykes P, Ormsby R, Tilley W The reduction of prostate cancer using 2009 $221,000; 2010 $207,000; 2011 $213,000 whole body low dose radiation Robertson SA, Gilchirst RB Discovery Grant: Molecular mechanisms for 2009 $72,250 seminal fluid signalling in reproduction Zannettino A, Hughes TP, Evdokiou A Can kinase inhibitors be used to 2009 $170,000; 2010 & 2011 $150,000 inhibit cancer-associated bone loss? Sumby CJ, Carver JA, Wallace JC, Hrmova M, Pring A, Abell AD, 2009 $93,000 Booker GW, Bruce MI, Brugger J, Ford CM, Harris HH, Morris JC, Cardiovascular Lipid Research Grant (Pfizer) Paton JC, Peet DJ, Pyke SM, Shearwin KE, Menz RI, Abbott CA, Anderson PA, Brown MH, Johnston MR, Schuller KA, Lopez AF, Puri R The in vivo validation of intracoronary salbutamol for coronary Pitson SM, Lincoln SF, McKinnon RA with partner organisations endothelial function testing and collaborating organisations: The University of Adelaide, The 2009 $50,000 Flinders University of South Australia, South Australian Museum, European Union/Cyprus Research Promotion Foundation Institute of Medical and Veterinary Science, University of South Odysseos A, Keramidas A, Evdokiou A Novel compounds of vitamin E Australia LIEF grant: The South Australian Facility for Small and Large and bisphosphonates: A promising new therapeutic approach in the treatment Molecule X-Ray Diffraction Structure Determination of bone loss associated with osteoporosis and bone related malignancies 2009 $560,000 2009 – 2011 $319,000 Australian Respiratory Council GlaxoSmithKline Hodge S ARC Harry Windsor Research Grant: Investigation of macrophage Keefe D Development of an animal model to study tyrosine kinase inhibitor- function as a therapeutic target in chronic obstructive pulmonary induced mucosal injury and diarrhoea disease/emphysema (COPD) 2009 – 2012 $620,000 2009 $50,000 Haemophilia Foundation Australia Cancer Council SA McRae S Thrombin generation in patients with discrepant haemophilia A Bianco-Miotto T W Bruce Hall Cancer Research Fellowship: Epigenetic 2009 $20,000 mechanisms and therapies in prostate cancer June 2009 – June 2010 $97,000 Helsinn Callen D, Braithwaite A Novel approaches to selectively revert cancer Keefe DMK, Gibson RJ Investigation of Palanosetron for the prevention of cells to a normal state chemotherapy-induced mucositis 2009 $105,500 2009 – 2010 $55,000 Cummins AG, Roberts-Thomson I, Hardingham J, Gibson R. Leukemia & Lymphoma Society, USA – Translational Research Intestinal stem cells Program 2009 $101,000. Zannettino A, Hughes TP, Evdokiou A, Fitter S Abl kinase inhibition D’Andrea RJ, Brown AL, Lewis ID, Mulligan CG, Bardy PG Klf5 as a novel therapy for myeloma-associated bone loss function in Acute Myeloid Leukaemia 2009 – 2011 $600,000 2009 – $98,188 Leukemia Research Foundation Goodall G Research Associateship in Microarray Bioinformatics funding Eadie L PhD Scholarship: Effect of combination and concomitant therapies in 2010 on transport and efficacy of nilotinib 2009 $22,000 2009 – 2011 $40,000 Goodall GJ, Farshid G The role of microRNAs in breast cancer metastasis Medvet Science Pty Ltd 2009 $101,526 Goodall G Fund 50% of Microarray Research Associate at the Adelaide Hardingham JE, Chataway T, Hewett P, Price T A new prognostic Microarray Facility multi-marker assay for early stage bowel cancer 2009 – 2010 $44,078 2009 $89,750 Goodall G The role of microRNAs in breast cancer metastasis Jamieson G, Drew P, Smith E, Devitt P, Kelly J, Liu J-F Improving 2009 $15,000 diagnosis and treatment of reflux and cancer of the oesophagus by studying Guthridge M The regulation of pleiotropic responses by bidentate motifs changes in microRNAs embedded in growth factor receptors 2009 $72,250 2009 $15,000 Kumar S, Cakouros D Controlling gene expression in normal and Pitson S Mechanisms of regulation and biological roles of sphingosine cancer cells kinase 2 2009 $101,500 2009 $15,000 Lopez A, Ramshaw H, Mullighan C Eradicating the leukaemic stem cell Schwarz Q Start Up Funds with a specific therapy 2009 – 2011 $269,645 2009 $89,750 Scott HS Using familial predispositions to haematological malignancies to Moore N Research Fellowship: Medroxyprogesterone acetate (MDA) action follow disease progression in the normal human breast: implications for breast cancer risk in users of 2009 $15,000 hormone replacement therapy Shandala T Innate immune response in Drosophila is regulated by June 2009 – June 2010 $87,000 14-3-3 proteins Pitson S Regulation and roles of sphingosine kinase 2 2009 $15,000 2009 $89,750

64 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH GRANTS COMMENCING 2009 of South Australia’s medical research

Zannettino A Abl kinase inhibition as a novel therapy for malignancy- Goodall G, Khew-Goodall Y Development Grant: Inhibition of metastasis associated bone loss by miR-200 2009 $15,000 2009 – 2010 $168,750 National Breast Cancer Foundation Grimbaldeston M The role of dermal mast cells in limiting the pathology Bracken CP Post Doctoral Fellowship: The role of the microRNA-200 family associated with chronic low-dose UVB irradiation of the skin in breast cancer metastasis 2009 – 2011 $142,250 2009 – 2012 $73,265 Gronthos S, Koblar SA, Matsuo K The role of Eph/ephrin interactions in Gregory P Early Career Fellowship: Identification and functional evaluation mediating mesenchymal stem cell commitment, migration and bone fracture of microRNAs involved in breast cancer metastasis repair 2009 – 2012 $160,031 2009 – 2011 $185,500 National Health & Medical Research Committee Guthridge M, Hughes TP A novel cytokine-receptor survival axis in chronic myeloid leukaemia Anderson RL, Khew-Goodall Y, Gregory PA, Johnstone CN 2009 – 2011 $136,000 Identification of genes that control the spread of breast cancer 2009 – 2011 $196,250 Guthridge M, Ekert PG Identifying the critical components of growth factor-mediated survival pathways Andrews RK, Cranmer SL, Ramshaw HS, Salem HH The role of 2009 – 2011 $195,500 platelet receptor glycoprotein Ib-V-IX in thrombosis 2009 – 2011 $192,250 Haynes DR, Atkins GJ, Howie DW, Crotti T Finding ways to make orthopaedic implants last longer Atkins GJ, Findlay DM, Bonewald LF, Anderson PH Osteocytes and 2009 – 2011 $129,250 bone health 2009 – 2011 $163,750 Hiller JE, Elshaug AG, Braunack-Mayer AJ, Moss JR, Wale JL, Buchan HA Changing policy and practice in health care Barry SC, Shannon F, D’Andrea R, Zola H To identify markers and key 2009 $250,250; 2010 $365,250; 2011 $245,250 genes required for regulatory T cell formation and function 2009- 2011 $174,583 Hughes T, Melo VJ, Branford S, White D Development and assessment of novel assays to predict response to second-line TKI therapy in Beckett EA Diabetes and the gastrointestinal tract imatinib-resistant CML 2009 – 2011 $127,258 2009 – 2011 $152,675 Blackshaw LA Principal Research Fellowship Levi CR, Sturm JW, Attia J, Scott RJ, Koblar SA, Lincz LF Genome- 2009 – 2013 $135,500 wide association study in stroke Bowen J Australian Based Biomedical Training Fellowship: Patient toxicity 2009 – 2011 $369,333 prediction:Indentification of mucosal injury mediators using microarray Lopez Program Grant: For research into better treatment for blood cell technology cancers such as leukaemia and inflammatory diseases 2009 – 2012 $71,250 2010 – 2014 $740,000 Coates PT, Kitching AR Dendritic cells in the kidney Morris H, Anderson PH, O’Loughlin PD, Atkins GJ The regulation of 2009 – 2011 $152,125 vitamin D-dependent bone metabolism Cooper D, Beard M, Dore G, Emery S, French M, Kelleher A, Kent 2009 – 2011 $196,125 S, Lloyd A, Purcell D Program Grant: HIV and HCV vaccines and Nalivaiko E, Day TA, Sanders P, Saint DA How chronic stress and Immunopathogenesis depression harm the heart 2009 – 2013 $3,315,836 2009 – 2011 $119,308 Coyle P, Rofe AM Prenatal alcohol exposure: A molecular mechanism for Page AJ, Blackshaw LA, Wittert GA Interactions of gastric hormones memory deficits involving the zinc-binding protein, methallothionein with vagal afferent pathways and the role of this system in obesity 2009 – 2011 $89,000 2009 – 2011 $166,500 Danthiir V, Wilson C, Nettelbeck TJ, Burns NR, Clifton PM The Parker MW, Hercus TR Studies to understand the activation of growth effect of omega-3 fatty acids on cognitive ageing in the elderly factors active in cancer and inflammation 2009 – 2011 $238,083 2009 – 2011 $199,000 Davey RA, Zajac JD, Morris HA Male hormone receptors in bone Reynolds PN, Hodge SJ, Clark HW Improving clearance of dead cells forming cells to treat chronic bronchitis and emphysema 2009 – 2011 $130,541 2009 – 2011 $157,600 Ekert PG, Scott HS Hox genes and myeloid leukaemia Robertson SA, Quayle AJ Seminal fluid and reproductive health 2009 – 2011 $190,500 2009 – 2011 $163,750 Evdokiou A, Findlay DM, Zannettino AC Novel strategies for the Rychkov GY, Koblar SA, Gronthos S, Kumar S, Blackshaw LA, treatment of bone cancer Brierley SM, Wilson DP, Beltrame JF, Peet DJ Equipment Grant: 2009 – 2011 $170,333 Patch clamping and imaging cells in tissue slices Feinle-Bisset C, Horowtiz M, Clifton PM, Rades T, Jones KL, 2009 $57,000 Rayner CK Lauric acid, a potential nutrient-based appetite suppressant Sanders P, Brooks AG, Young GD Efficacy of coronary sinus ablation for 2009 – 2011 $238,000 treatment of atrial fibrillation Feinle-Bisset C, Clifton PM, Horowtiz M, Jones KL, Wittert G 2009 – 2011 $121,313 Effects of acute and longer-term dietary changes on gut function and appetite White JM, Nettelbeck TJ, Burns NR, Somogyi AA Cognitive effects of in lean and obese subjects opioid drugs 2009 – 2011 $271,333 2009 – 2011 $126,758 Gibson PG, Simpson JL, Upham JW, Reynolds PN, Yang IA, Wood JP, Chidlow G, Casson RJ The role of Tau in experimental retinal Hodge SJ The AMAZES study: Asthma and Macrolides: the AZithromycin and optic nerve pathology: Relevance to glaucoma Efficacy and Safety study 2009 – 2011 $120,250 2009 – 2013 $671,250

65 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH GRANTS COMMENCING 2009 of South Australia’s medical research

Wood AW, Finnie JW, Ueno S Does mobile phone radiation affect brain Callen D Clinical Project Grant: A breast tissue resource for methylation processes? studies on chromosome 16q and determining vitamin D metabolism in 2009 – 2011 $78,750 breast tissues Hoffmann P, McColl SR, Oehler MK, Findlay DM, Evdokiou A, 2009 $25,000 Lopez A NHMRC Equipment Grant: Facility for matrix deposition on tissue Carr J, Pitson S, Li P, Burrell C Bridging grant: The role of altered TNF sections for imaging mass spectrometry responses in the severity of DV infection 2009 $43,760 2009 $50,000 National Heart Foundation Cooper L Dawes Postgraduate Biomedical Scholarship (top-up): The Brooks A Complex electrograms in atrial fibrillation: what are their identification of genes and signalling pathways regulated by Twist-1 and mechanisms? Dermo-1 that mediate mesenchymal stem cell growth, survival and 2009 $125,000 differentiation 2009 $15,000 Faull R, McKenzie L, Sanders P Atrial remodelling in an ovine model of chronic reno-vascular hypertension: implications for atrial arrhythmogenesis Dundon B Clinical Project Grant: Evaluation of cardiac risk and alterations 2009 – 2010 $64,400 in coronary structure and function in end stage renal failure 2009 $16,425 Sanders P Implications of left atrial stretch in the development of atrial fibrillation Eadie L Dawes Postgraduate Biomedical Scholarship (top-up): Studies of 2009 $124,950 the cellular transport of nilotinib 2009 $15,000 Nestec Ltd Faull R Honours Scholarship: Calcium absorption in renal transplant Keefe DMK, Bowen JM, Schiffrin E Investigation of effect of nutritional recipients drink on chemotherapy-induced mucosal injury and tumour growth 2009 $2,000 2009 – 2010 $178,809 Fazzalari N Bridging Grant: Mechanisms of osteoarthritis: altered Keefe DMK, Bowen JM, Schiffrin E Development of a fractionated subchondral bone remodelling radiotherapy model to assess treatments for chronic intestinal radiation 2009 $50,000 injury 2010 – 2011 $180,781 Grimbaldeston M Florey Fellowship: Skin mast cells and vitamin D3: Immunomodulatory functions associated with chronic low-dose UVB Ophthalmic Research Institute of Australia (ORIA) irradiation Casson R, Blumbergs P The effect of glucose on experimental glaucoma 2009 – 2011 $109,600 2009 – 2010 $69,030 Grimbaldeston M Clinical Project Grant: Does Vitamin D3 potentiate IgG- Wood J, Chidlow G, Casson R The role of Tau in experimental glaucoma induced interleukin 10 production by human mast cell? 2009 $50.000 2009 $23,930 Pfizer Australia Pty Ltd Helbig K Clinical Project Grant: Chemokine antagonists of inflammation in Thomas D Targetting cell survival pathways in chronic myeloid leukaemia chronic HCV infection 2009 $48,500 2009 $20,000 Prostate Cancer Foundation of Australia Howie D Clinical Project Grant: The precision of using RSA to measure Day TK Young Investigator Grant: Androgen receptor signalling in prostate movement of tantalum Trabecular Metal acetabular components in total hip cancer tumourigenesis replacement 2009 – 2013 $122,802 2009 $20,000 Royal Adelaide Hospital/SA Pathology Research Committee Jesudason C Allied Health Grant: An evaluation of the effectiveness of physiotherapy service to the emergency Extended Care Unit (EECU) Alsharifi M Mary Overton Award 2009: Flu vaccine formulation and viral 2009 $32,639 antigenic variations 2009 $50,000 Kernick J Allied Health Grant: High flow nasal oxygen or non-rebreather mask – A randomised controlled trial Andrews J Clinical Project Grant: What are the relationships amongst 2009 $17,335 factors associated with; (a) reduced patient satisfaction and (b) increased adverse outcomes in Inflammatory Bowel Disease (IBD)? – An exploratory McRae S Mary Overton Award 2009: Thrombin generation in multiple study of patient's perceptions of medical and surgical care. myeloma 2009 $20,000 2009 $50,000 Atlantis E Early Career Fellowship: The effects of a worksite wellness Murray J Allied Health Grant: Stroke patients who aspirate thin liquids – program on psychological health and body fat outcomes: a randomized A comparison of outcomes of current and emerging practice control trial 2009 $33,000 2009 – 2011 $87,000 Puri R Dawes Postgraduate Medical Scholarship (top-up): Dynamic Bochner M Clinical Project Grant: The impact of Tamoxifen CYP2D6 structural and functional studies of human coronary arteries in vivo metaboliser status on breast cancer outcome in women treated with 2009 $15,000 Tamoxifen for early breast cancer Ruszkiewicz A Clinical Project Grant: Evaluation of immunohistochemical 2009 $20,000 markers of sessile errated adenoma in routine histopathological testing Bonder C Florey Fellowship: A novel pathway controlling endothelial 2009 $24,220 progenitor cell fate Slobodian P Clinical Projects Grant: Serum equilibration time on standard 2009 – 2011 $109,600 vitamin D treatment Butler L Clinical Project Grant: A novel explant model for the investigation 2009 $20,000 of hormone signalling and novel treatments in human prostate tissue Solomon L Clinical Project Grant: Abductor muscles function after hip 2009 $20,000 arthroplasty. A clinical testing, EMG and MRI study 2009 $20,000

66 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH GRANTS COMMENCING 2009 of South Australia’s medical research

Storer K Allied Health Grant: A prospective study to demonstrate that earlier and more regular investigation of known risk factors of delayed wound healing may improve early management of non-traumatic foot amputations in patients with Type II Diabetes 2009 $6,468 Thomas D Clinical Project Grant: Validation of stromal survival cytokine, Spp1 (Osteopontin), as a novel prognostic marker in acute myeloid leukaemia 2009 $17,000 Torpy D Clinical Projects Grant: The effect of continuous subcutaneous hydrocortisone infusion (CSHI) pump therapy in Addison’s Disease on subjective health status: A double-blind, randomised, placedo-controlled clinical trial 2009 $25,000 Zinonos I Dawes Postgraduate Biomedical Scholarship (top-up): Efficacy of Apomab, a fully human agosistic TRAlL death receptor DR5 monoclonal antibody, in animal models of skeletal malignancies. 2009 $15,000 Royal Adelaide Hospital/SA Pathology Research Committee/University of Adelaide Seimon R Dawes Postgraduate Biomedical Scholarship: Oral and small intestinal sensitivity to dietary fats in lean and obese humans and the responses to acute and longer-term dietary restriction – implications for energy intake regulations in obesity 2009 $15,000 SA Premier’s Science and Research Fund Marshall R, Clark J Exercise to promote neural recovery following spinal cord injury: acute care to the community 2009 – 2011 $198,240 The Clive and Vera Ramaciotti Foundations Horowitz M Proposal for One 2020tc single head camera 2009 $30,000 The Queen Elizabeth Hospital Research Foundation Hardingham J, Townsend A, Price T Over-expression of SET is a critical factor in Wnt/‚-catenin signalling in colorectal cancer 2009 $20,000 Raynor M, Dobrovic A Analysis of DNA in plasma as a new methodology for early detection and monitoring of cancer 2009 $20,000 University of Adelaide Faculty of Health Sciences Logan RM, Bowen JM Investigating the role of pro-inflammatory mediators in the pathogenesis of cancer treatment-induced mucosal injury 2009 2010 $8,000 Bowen J, Gibson R Seed funding for new contract research 2009 $26,000 Gibson R Seed funding 2009 $10,000 Sweeney C, Lopez A, To LB, Tilley W et al Adelaide Cancer Research Institute 2009 – 2013 $1,000,000

67 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Amgen Australia Pty Ltd Australian Orthopaedic Association Research Foundation Lewis I Assist in the development of templates for all commonly used Howie DW, Holubowycz O, Callary SA Polyethylene wear and chemotherapy regimes at Royal Adelaide Hospital migration of acetabular components following total hip replacement with a 1/8/2008 – 30/9/2009 $29,091 large articulation Archdiocese of Sydney 2008 – 2009 $23,225 Gronthos S, Koblar S Adult stem cell research Howie D, McGee M, Taylor J The detection of periprosthetic osteolysis 2008 – 2009 $100,000 around total knee replacements in a human cadaver model 2007 – 2008 $26,955 Arthritis Australia Solomon LB, Chehade MC, Howie DW, Callary SA, Carbone T, Bonder C The Allan Stephens Grant: Cellular recruitment in rheumatoid Stevenson A A review of treatment methods and radiographic and clinical arthritis: a role for sphingosine kinase outcomes of patients with tibial plateau fractures 2008 $15,000 2008 – 2009 $28,725 Lester S, Rischmueller M Genetic determinants of type I interferon Australian Research Council responses in primary Sjogren’s syndrome and systemic lupus erythematosus 2008 $50,000 Semple SJ, McKinnon RA, Wang J, Claudie DJ Linkage Project: Pharmacological investigation of medicinal plant products from Kaanju Association for International Cancer Research, UK Homelands, Wenlock and Pascoe Rivers, Cape York Peninsula Woodcock J, Guthridge M The role of dimeric 14-3-3 in AML 2006 – 2008 $50,000 blast survival Bi P, Ryan P, Hiller JE, Roder D, Han G, Collaborating/Partner October 2005 – September 2008 $74,137; $76,137; $78,584 Organisations: SA Department of Health & Migrant Resource Astra Zeneca AB Centre South Australia Linkage Project: Changing disease patterns Blackshaw LA Third research program: Transient lower oesophageal amongst migrants: a focus on the National Health Priority sphincter relaxation in gastrointestinal disorders 2008 – 2010 $25,627 2008 – 2009 $665,724 Braunack-Mayer AJ, Rogers W, Moss JR, Hiller JE, Bi P, Salter Australian Agency for International Development AB, Givney RC, van Eyk H Linkage Project: Citizens’ juries: enabling Newland H, Muecke J, Selva D, Casson R Reducing preventable effective influenza pandemic policy through engagement with the community blindness in Burma by Vision Myanmar Program 2007 $32,000; 2008 $52,000 July 2007 – June 2011 $295,318 Brewer N, Young RL, Weber N, Ma-Wyatt AM, Semmler C, Australian Centre for Hepatitis & HIV Virology McKinnon RA, Partner Organisations and Collaborating Organisations: Flinders University of South Australia, University Carr JM, Qiao M, Shaw D, Higgins G, Li P ACH2: Application of an of Adelaide and University of South Australia LIEF Project: A multi- HIV allele-specific quantitative RT-PCR for study of low frequency function eye-tracker facility antiretroviral resistance mutations 2008 $120,000 2007 – 2008 $73,000 Brooks DA, Shearwin KE, McKinnon RA, Parkinson-Lawrence EJ, Australian Dental Research Foundation Wallace JC, Evans AM, Peet DJ, Morona R, Whitelaw ML, Ecroyd Menicanin D, Gronthos S, Bartold PM HW, Pitson SM, Lopez AF, Forbes BE, Sumby CJ, Morris HA, Genomic characterisation of mesenchymal stem cells present in human bone Hopwood JJ, Partner Organisations and Collaborating marrow and dental pulp tissues Organisations: University of South Australia, University of 2008 $7,600 Adelaide, Institute of Medical and Veterinary Science, Adelaide Wada N, Mrozik K, Gronthos S, Bartold PM Immunosuppressive Women's and Children's Hospital, AIB Laboratories (Bio mechanisms of allogeneic periodontal ligament stem cells on T-lymphocytes Innovation SA) LIEF Project: Biophysical Characterisation Facility 2008 $7,500 2008 $245,000 Australian Cancer Research Foundation Callen D, Morris HA, Collaborating partner: SA Pathology Linkage Project: Determining the regulation of vitamin D metabolism McColl S, Hoffmann P, Wallace J, Lopez A, Gamble J Adelaide 2008 – 2010 $92,000 Proteomics Centre 2006 – 2010 $300,000 Croft K, James M, Novogen Ltd Linkage Project: Structure-activity Australian Lung Foundation relationships in the development of new bioactive isoflavonoids 2006 – 2008 $25,000 Hodge S The Australian Lung Foundation COPD Research Award: Fazzalari N, Voelcker N, Lal R Discovery Project: Material structure and Alternative alveolar macrophage phenotype and function in COPD patients properties of mineralised tissue: an integrated micro and nano level with/without lung cancer - implications for tumour susceptibility and investigation progression 2008 – 2010 $125,460 1/4/2008 – 31/3/2009 $100,000 Griesser HJ, Thierry B, Prestidge CA, Brown MP, Tabrizian M Reynolds P The Australian Lung Foundation Melbourne Community Discovery Project: Advanced nanostructured biointerfaces for cell capture Foundation-Slater & Gordon Asbestos Research Fund Asbestos Research 2008 $150,000; 2009 $130,000; 2010 $130,000; 2011 $125,000 Grant-in-aid: Does replicative viral therapy synergize with immunotherapy in mesothelioma Hayball JD, Brown MP, Howley PM. Industry partner: Virax 2008 $30,000 Holdings Limited Linkage Project: Improving and manipulating the Australian National University immune adjuvant properties of recombinant fowlpox vectors 2005 – 2008 $27,500 Kuchel T Equipment for Mouse Phenomics Agreement James MJ, Gibson RA Discovery Project: Omega-3 fats in vegetable oils: October 2007 – September 2012 $200,000 Improving their benefits 2008 $85,000; 2009 $87,500; 2010 $85,000

68 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Karnon JD, Beilby J, Holton CH, Hakendorf PH, Ben-Tovim DI, Cleland L Employment of Research Officer and related maintenance costs Ryan P, Eckermann SD, Sawyer MG, Roos NP, Woollacott AL, 2008 $77,000 Banham DM, Pegram R, Thompson S, Elshaug AG. Fitter S Kia Marina Cruise for Myeloma Research Fellowship Collaborating/Partner Organisations: Department of Health SA, 2008 – 2010 $60,000 Department of Education and Children’s Services, Central Commonwealth Serum Laboratories Northern Adelaide Health Service Linkage Project: Evaluating the long-term costs and benefits of community-based initiatives Lopez A GM-CSF receptor site 4 2008 – 2011 $100,000 plus partner contributions: 2008 $50,000; 2009 2008 – 2010 $482,437 $100,000; 2010 $100,000; 2011 $50,000 Cooperative Research Centre for Biomarker Translation Mackenzie L, Sanders P Discovery Project: Electrophysiological and Lopez AF, Bonder CS, Pitson SM CRC for Biomarker Translation anatomical characterization of the coronary sinus musculature and its 2008 – June 2009 $332,634 relationship to the atria CRC for Contamination Assessment and Remediation of the 2008 – 2010 $147,000 Environment (University of South Australia) Nettlebeck TJ, Burns NR, Wittert GA Smith E, Juhaz A, Rofe AM Bioavailability models for quantifying human Discovery Project: Declining mental efficiency, cognitive performance and health risk individual differences in aged function 2006 – 2008 $480,000 2007 – 2009 $83,000 Croucher Foundation Poronnik P, Kumar S Discovery Project: Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and Cheung KC PhD scholarship transporters 1/7/2008 – 30/6/2011 2008 – 2010 $180,000 CSIRO Reynolds KJ, Fazzalari NL, Bottema MJ, Hearn TC, Cleek TM Ruszkiewicz A, Moore J, Cosgrove L, Fung K, Beard M Flagship Discovery Project: Three-dimensional simulation of trabecular bone project: Identifying protein markers of serrated adenomas using proteomics remodelling September 2007 – October 2008 $100,000 2006 – 2008 $80,000 Curtin University of Technology Winefield H Linkage Project: Optimal Resourcing: A longitudinal study of Briggs AM, O'Sullivan PB, Wark JD, Fazzalari NL, Dillon D, work demands, resourcing, and psychological well-being in Australian Buchbinder R, Smith AJ. Curtin University of Technology frontline police officers Impaired bone health in the context of chronic back pain: An exploratory 2005 – 2008 $12,074 study Winefield AH, Delfabbro PH, Dollard MF, Winefield HR, Metzer 2008 – 2009 $12,000 JC, Hammarstrom A Discovery Project: Transition from school to work: Daw Park Foundation A 10 year longitudinal study of unemployment, underemployment, social Fraser R Does an improvement in drooling severity following treatment exclusion, and mental health in young people correspond to benefits in patient perceived quality of life in Parkinson’s 2008 – 2012 $104,915 Disease? BioInnovation Project - State Government Funding 2008 $10,000 Brown M A method of diagnosis and treatment and agents useful for same Department of Further Education, Employment, Science and 2008 $20,000 Technology Goodall G, Richards R, Rudzki Z, Koblar S, Keefe D, Kuss B, Kuchel T Large Animal Imaging Facility (LARIF) D’Andrea R Fund 50% of Microarray Research Associate at the Adelaide October 2007 – September 2012 $963,000 Microarray Facility Kuchel T Mouse Phenomics Agreement July 2006 – June 2008 $43,538; $44,835 October 2007 – September 2012 $200,000 Goodall G, Khew-Goodall Y Commercial Development initiative: Department of Health Blocking tumour invasion and metastasis with microRNAs 1/4/2008 – 31/3/2009 $50,000 Nordin BEC Vitamin D and calcium project 1/7/2008 – 30/6/2009 $20,000 Ratcliff RM, Higgins GD, Arthur JL Development of an antigen capture enzyme immuno-assay (EIA) for a novel Adelavirus Department of Health and Ageing 1/6/2008 – 31/7/2009 $60,000 Beilby J, Laurence C et al Role of Point of Care Testing in Australian Bristol Meyer Squibb General Practice 2006 – 2008 $1,666,666 White DL, Hughes TP ALL5 correlative substudy 2008 – 2010 $182,000 DePuy Australia/Johnson & Johnson White DL, Hughes TP Investigation into the drug transport proteins Brumby S, Fowler S, Duncan W, Van Essen J, O’Brien J, Standen involved in the uptake of dasatinib A, Carbone A, McGee MA Computer navigated total knee replacement 2008 – 2010 $169,464 surgery 2007 – 2008 $33,712 Clive and Vera Ramaciotti Foundation DePuy Spine Horowitz M, Fraser R, Rayner C, Jones K Contribution towards a 2020tc single-head imager 30000 (camera and software) Mulaibrahimovic A, Moore RJ Biomechanical and neurophysiological 2008 $30,000 responses of mechanical stimulation via spinal manipulation in an ovine model of lytic spondylolisthesis Commissioner of Charitable Funds 2007 – 2008 $35,000 Brown M Support for Laboratory Manager Diabetes Australia Research Trust 2008 $70,000 Young RL Characterisation of intestinal sweet taste molecules in type-2 diabetes 2008 $49,730

69 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Drug & Alcohol Services Council Medtronic Davey M RAH Emergency Department Designer Drug Early Warning System Moore RJ Local bone regeneration in the vertebrae in the osteoporotic Research Project (D2EWS) ovine model using rhBMP-2/POE delivery: a pilot study 2007 – June 2008 $39,153 2007 – 2008 $319,180 Ellex Medical Pty Ltd Medvet Science Pty Ltd Casson R The effects of nanosecond laser pulses on the rat retina D’Andrea R Start-up grant to support the establishment of the Acute May 2007 – April 2008 $20,000 Leukaemia Laboratory Fay Fuller Foundation 2008 – 2012 $100,000 Leclercq T Fay Fuller Fellowship Dunn K Fellowship for Psychiatry 1/7/08 – 30/6/2011 $70,000 2008 – 2010 $100,000 Pitson S Fay Fuller Fellowship Elshaug A Fellowship for Public Health 2007 – 2010 $100,000 2008 – 2010 $100,000 GlaxoSmithKline Australia Pty Ltd Goldney R Mental Health Survey: Major depression in South Australia: trends in prevalence, morbidity, mental health literacy and costs to the Keefe D Development of an animal model to study tyrosine kinase inhibitor- community induced mucosal injury and diarrhoea 2008 $157,000 1/10/2008 – 31/12/2011 $219,000 Scott H Start-up grant Haematology Private Practice Fund 2008 – 2012 $100,000 Zannettino A Development of a therapeutic optamer that antagonises SDF- Mesoblast Ltd and Australian Government AusIndustry 1 (CXCL12) binding to the CXR0 September 2007 – August 2008 $27,000 Moore RJ, Gronthos S, Zannettino ACW, Melrose J, Pearcy MJ A preclinical trial of the potential for cultured mesenchymal precursor cells to Hunter Area Health Service restore extracellular matrix and normal mechanical function to degenerate Lopez A Chronic Fatigue Syndrome as a manifestation of the post- intervertebral discs infectious fatigue complex: new models from Coxiella and Rickettsial 2007 – 2008 $570,589 infections National Breast Cancer Foundation of Australia May 2007 – April 2008 $25,000 Betterman K The identification of genes important for lymphatic vascular Inner Wheel Australia remodelling during mammary gland development Barry SC, D’Andrea RJ, Lewis ID Differentiation of cord blood stem 2008 – 2010 $32,003 cells into regulatory T cells for cell therapy Callen D 2008 $57,000 The role of FBXO31 in a novel pathway of breast tumour suppression Juvenile Diabetes Research Foundation/Australian Federal 2008 $70,000; 2009 $178,000 Government Clarke C, Tilley WD, Leedman P, Fuller P, Muscat G, Funder J, Russ G, Coates TPH, Torpy DJ et al SA/NT islet cell transplant program Ragan M, Simpson E, Rosenthal Identification of nuclear receptor ‘Clinical Islet Transplantation’ networks as new targets for breast cancer treatment 2006 – 2009 $723,641 2008 – 2012 $1,328,000 (yr1), $1,838,000 (yrs 2 & 3), $2,100,000 (yr4&5) Leukemia Research Foundation Evdokiou A, Findlay DM, Butler L TRAIL in breast cancer therapy Engler J Scholarship: Factors which control targeted drug uptake into 2006 - 2008 $97,000 CML cells Hickey TE & Tilley WD Medroxyprogesterone acetate (MPA) is an 2007 – 2008 $40,000 endocrine disruptor of androgen receptor signaling in breast. Hughes T Developing predictive assays to select second line therapy in October 2008 – October 2010 $100,000 imatinib resistant CML Hiller J, Hayes S, Kilbreath S, Cornish B, Pillar N, Speakman D, 2008 $81,225 Achen M Collaborative Breast Cancer Research Grant Program: Researching Lim H Honours scholarship: Identification of prognostic markers and lymphoedema following breast cancer in Australia: A strategic plan for therapeutic targets in acute myeloid leukaemia improving understanding through evidence-based research 2008 $10,000 2008 $15,000 Ross D Scholarship: Characterisation of leukaemic CML cells remaining Tilley WD, Butler LM, Roder DM, Farshid G Androgen receptor status after treatment as a determinant of breast cancer risk 2006 – 2008 $40,000 2006 $34,000; 2007 $110,000; 2008 $110,000 Sadras T Honours Scholarship: Dissecting the role of beta-catenin in FLT3- National Collaborative Research Infrastructure Scheme (NCRIS) ITD AML Morris HA, Kuchel T, Vink R Large Animal Research and Imaging 2008 $10,000 Facility (LARIF) Lions Medical Research Foundation 2007 – 2011 $213,000 plus $380,000 co-investment SA Government Carter S Novel combination strategies for the treatment of prostate cancer (DFEEST) 2007 – 2009 $30,000 Lewis I, To LB Therapeutic Products Facility MBF Foundation Ltd 2007 – 2011 $125,000 Wittert G, Worthley S, Piantadosi C, McAinch A The safety efficacy of National Health & Medical Research Council rapid weight-loss using a modified very low calorie diet, followed by a Alderuccio F, Scott H, Huber F-X The role of Aire in immunological weight maintenance strategy, on cardiovascular risk factors – ‘Healthy Weight tolerance and autoimmunity for Life Project’ 2008 – 2010 $138,875 2007 – 2009 $48,985 Atkins G, Findlay D, Haynes D, Zheng T, Zannettino A The role of TNF family members TWEAK and TNF-alpha in bone remodelling 2007 – 2009 $181,500

70 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Atkins G Career Development Award: The cell and molecular biology of Clifton P, Noakes M, Brinkworth G, Buckley J, Fenech M, human bone remodelling Wilson C Long-term efficacy and safety of low-carbohydrate diets 2007 – 2011 $89,000 2006 – 2008 $162,917 Barr R Peter Doherty Fellowship: Defining the relationship between Cook N Biomedical Postgraduate Scholarship: Characterisation of sphingosine kinase regulation and oncogenic signalling neuropeptide messenger RNA and TRPM7 channels in acute and chronic 2007 – 2011 $68,500 neurological disorders Barry SC, Shannon F, Zola H, D’Andrea RJ The molecular 2007 – 2009 $21,866 identification of FoxP3 positive regulatory T cells D’Andrea R, Scott H, Bardy P, Melo J Molecular genetics of 2006 – 2008 $154,250 polycythemia vera Bartold P, Gronthos S, Zilm P Periodontal ligament stem cells 2008 – 2010 $204,000 2007 – 2009 $195,000 D’Andrea R, Gonda T Dissecting FLT3 signalling in acute myeloid Beard M R Douglas Wright Career Development Award: Defining the leukaemia hepatocyte response to HCV infection: its role in modulating liver disease 2007 – 2009 $159,500 and virus replication Davey R, Zajac J, Findlay D, Morris H, Karsenty G The 2005 – 2009 $89,000 physiological role of calcitonin and its receptor in bone cell metabolism Beard M, Jones B The role of Cyp2e1, alcohol and HCV in modulation of 2007 – 2009 $159,000 hepatocyte homeostasis HCV replication and resistance of interferon Dimitri H NHMRC/NHF Training Postgraduate Scholarship: Obstructive 2006 – 2008 $74,250 sleep apnoea and atrial fibrillation Beard M, McColl S, Qiao M The role of CXCR3 chemokines in hepatitis 2008 – 2009 $31,422 C and other forms of viral hepatitis Dodd J, Turnbull D, McPhee A, Wittert G, Robinson J Limiting 2006 – 2008 $149,250 weight gain in overweight and obese women during pregnancy to improve Beard M, Helbig K Identification of interferon stimulated genes that limit health outcomes – a randomised trial HCV replication and predict therapeutic outcome 2008 – 2011 $488,875 2008 – 2010 $124,500 Dundon B NHMRC/NHF Training Postgraduate Scholarship: Assessment of Beard M, Whitelaw M, Paton J, Peet D, Evdokiou A Zannettino A the role of kidney transplantation in improving cardiovascular health in renal Equipment grant: Kodak chemiluminescence and gel imaging system failure (40000MMPro Image Station) 2008 – 2009 $31,422 2008 $55,000 Ernst M, Hoffmann P Validation of Stat3 as a therapeutic target in Bianco-Miotto T Peter Doherty Fellowship: Protective role of androgen diseases arising from its inappropriate activation by gp130 cytokines signalling breast cancer 2007 – 2009 $215,083 2005 – 2008 $66,000 Evdokiou A R Douglas Wright Biomedical Career Development Award: Blackshaw LA, Brierley S, Rychkov G, Holtmann G Transient Novel approaches to bone cancer therapy receptor potential channels (TRPs) as transducers and targets in primary 2005 – 2009 $85,250 visceral afferents Evdokiou A, Findlay D Targeting the vicious cycle of cancer-induced bone 2008 – 2010 $177,000 disease with TRAIL and bisphosphonates Blackshaw LA Senior Research Fellowship (Level B) 2007 – 2009 $142,250 2006 – 2010 $119,000 Evdokiou A, Findlay D, Butler L Histone deacetylase inhibitors (HDIs) Blackshaw LA, Brookes S, Brierley S, Page A How does inflammation with antineoplastic and antiosteolytic properties of the gut change its sensory innervation? 2008 – 2010 $171,250 2006 – 2008 $204,431 Faull R Benefits of intravenous L-carnitine supplementation in long-term Bonder C Peter Doherty Fellowship: The role of the sphingosine kinase and haemodialysis patients endothelial cell activation in autoimmune diseases 2008 – 2010 $133,500 2005 – 2008 $69,750 Fazzalari N, Kuliwaba J Intrinsic bone qualities in fragility fracture Bonder C New Investigator Grant: Role for sphingosine kinase-1 endothelial patients: mass, microarchitecture, mineralization and damage accumulation progenitor cell survival and differentiation 2006 – 2008 $142,503 2007 – 2009 $88,350 Fazzalari N, Kuliwaba KS, Parkinson IH, Smith P Vertebral body Brierley S Training Postgraduate Fellowship: Interaction of TRP channels strength: Contribution of bone mass, bone structure and material properties and inflammatory mediators: a critical role in visceral pain 2008 – 2010 $142,375 30/6/2008 – 30/6/2013 $69,750 Feinle-Bisset C Clinical Career Development Award: Relationship between Brooksbank M Pallative Care Grant: Informing the development of a model diet, symptoms and gastric motor function in functional dyspepsia of care for patients with end stage COPD: what are their care needs and are 2004 – 2008 $80,000 they being met? Findlay D, Haynes D, Howie D, Atkins G, Crotti T Impaired bone 2008 – 2010 $39,725 remodelling leads to failure of orthopaedic prostheses Buchanan G CJ Martin Fellowship: In vivo regulators of androgen receptor 2006 – 2008 $164,500 function in prostate cancer Finnie J, Blumbergs P, Kuchel T Centre of Excellence: Australian Centre 2006 – 2009 $66,000 for Radiofrequency Bioeffects Research Chidlow G, Wood J, Casson R Role of osteopontin in ischemic-like 2004 – 2008 $89,350 injury to the retina Forwood M, Fazzalari N, Kuliwaba J Influence of anti-inflammatory 2008 – 2010 $114,438 treatments on healing of stress fractures Clements J, Sutherland R, Risbridger G, Tilley WD Enabling 2006 – 2008 $133,250 Grant: Australian Prostate Cancer Collaboration Bio-Resource Foster P, Lopez A Targeting the shared beta-chain of the IL-3, IL-5 and (Hanson Institute Node) GM-CSF receptors as therapy for allergic inflammation July 2004 – June 2009 $84,000 2008 – 2010 $195,125

71 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Fraser R, Chapman M, Rayner C, Holloway R, Holtmann G, Hill C, Cleland L, Jones G, March L Fish oil in the treatment of knee Horowitz M Impact of gastrointestinal dysmotility on enteral nutrition in the osteoarthritis critically ill 2007 – 2009 $206,250 2008 – 2010 $150,500 Hodge S Biomedical Career Development Award: Investigating the causes of Gagliardi L Scholarship: Adrenal Cushing’s: Natural history and genetic failed efferocytosis in COPD/emphysema with a view to identifying novel analysis of inherited forms, and prevalence in high risk groups therapeutic targets 2008 $32,003 31/3/2008 – 30/3/2012 $92,500 Gentilcore D Australian Clinical Research Fellowship: Effects of exercise Hoffmann P Equipment grant: Facility for matrix deposition on tissue on gastrointestinal function and postprandial blood pressure in the elderly sections for imaging mass spectrometry 2007 – 2010 $68,500 2008 $29,000; Faculty Endowment income $10,000; RIBG $5,000 Gilbert G, Reeves P, Sintchenko V, Lan R, Kong F, Holtmann G, Holloway R, Talley N, Gericke C, Fraser R, Adam B, Heuzenroeder M Optimisation of Salmonella genotyping and Liebregts T, Beilby J Complementary and Alternative Medicine Grant: A epidemiological data analysis for detection and investigation of outbreaks randomised placebo-controlled trial of a herbal preparation in functional 2007 – 2009 $149,500 dyspepsia: cost effectiveness and mechanisms Gill G SNAC2: A randomised trial of extending sentinel node based 2008 – 2010 $243,965 management to women with larger or multifocal breast cancers Holtmann G, Holloway R, Talley N, Liebregts T, Adam B, 2008 – 2012 $1,185,213 Siffert W Life-threatening ulcer complications in the elderly: role of visceral Gill G, Wetzig N, Gebski V, Ung O, Campbell I, Oliver D SNAC1: sensory function and molecular mechanisms A randomised trial of sentinel node based management versus axillary 2008 – 2010 $142,375 clearance for women with breast cancers Horowitz M, Clifton PM, Wittert GA, Chapman I, Fraser RJ, 2007 – 2009 $78,500 Rayner CK, Feinle-Bisset C, Jones KL Clinical Centre of Research Gill G, Wetzig N, Ung O, Bilous M, Campbell I, Collins J, Hague Excellence: CCRE in nutritional physiology, interventions and outcomes W, Kirby A SNAC1: A randomised trial of sentinel node based management 2007 – 2011 $400,000 versus axillary clearance for women with small breast cancers Horowitz M, Jones K, Rayner C, Feinle-Bisset C, Smout A, 2008 – 2010 $424,283 Samsom M Upper gastrointestinal motility and glycaemic control in Goodall G, Shannon F, Khew-Goodall Y, Ruszkiewicz A Regulation diabetes mellitus of expression of the microRNA-200 family 2007 – 2009 $174,000 2008 – 2010 $183,500 Howie D, Nivbrant B Radiostereometric analysis of the effect of a large Gregory P Peter Doherty Fellowship: MicroRNA regulation of genes articulation on prosthetic wear and migration after hip replacement involved in angiogenesis 2008 – 2010 $61,200 2005 – 2008 $68,500 Howie D, Field J, Forwood M, Morgan D, McGee M, Hearn T Griesser H, Thierry B, Brown M, Majewski P, Taylor D Determination of irradiation dose efficacy for use in impaction grafting at Immunotargeted nanoparticles to improve tumour delivery of revision joint replacement chemosensitising cytotoxic drugs and beta-radiation 2007 – 2009 $131,000 2008 – 2010 $173,500 Hughes T Practitioner Fellowship Grimbaldeston M CJ Martin Fellowship: Regulation of cutaneous gene 2008 – 2012 $83,100 expression by mast cells Hughes T, Melo J The role of intracellular uptake and retention of Abl August 2007 – July 2009 $68,500 kinase inhibitors in modifying clinical response in CML Gronthos S Research Fellowship 2007 – 2009 $151,850 2008 – 2012 $107,500 James M, Gibson R, Cleland L, Cook-Johnson R, Lester S Gronthos S, Zannettino A, Fazzalari N The role of TWIST family of Regulation and activity of fatty acid delta-6-desaturase (D6D) basic-helix-loop transcription factors in bone cell commitment, function and 2007 – 2009 $172,250 repair James M, Sanders P, Young G, Edwards J, Metcalf R, Gibson R 2007 – 2009 $157,050 Effects of n-3 polyunsatuarated fatty acids on post surgical atrial fibrillation: Gururatsak M Training Postgraduate Scholarship: Gastroesophageal A prospective randomised study sensory function in patient with complicated and uncomplicated peptic ulcer 2006 – 2008 $178,969 and gastroesophageal reflux Jeffs L Medical Postgraduate Scholarship: The pathogenesis of Wegener’s 2008 – 2009 $32,003 granulomatosis and microscopic polyangiitis Guthridge M The role of the phosphorylated Ser/Tyr bidentate motif in 2005 – 2008 $29,071 leukemia and myeloproliferative disorders Jilbert A Mason W, Harley H Clonal proliferation of hepatocytes and 2007 – 2009 $83,900 progression of liver disease in chronic hepatitis B virus infection Guthridge M The regulation of pleiotropic responses by phospho-Ser/Tyr 2007 – 2009 $136,625 binary switches embedded in growth factor receptors Jilbert A Immune therapies for chronic hepatitis B virus infection 2006 – 2008 $106,735 2007 – 2009 $117,325 Harrich D, Warrilow D, Li P Early events in HIV reverse transcription Jilbert A Mason W Resolution of acute hepatitis B virus infections 2008 – 2010 $203,000 2007 – 2009 $117,325 Harvey NL New Investigator Grant: Molecular mechanisms of Jones K, Horowitz M, Chapman I, Feinle-Bisset C, Rayner C lymphangiogenesis in development and disease Pathophysiology of postprandial hypotension in the elderly – role of ‘gastric’ 2007 – 2009 $99,200 and ‘small intestinal’ mechanisms Helbig K Peter Doherty (Biomedical) Fellowship: Host factors modulating 2007 – 2009 $150,000 the severity of Hepatitis C virus infections Kleinig T NHMRC/NHF Postgraduate Scholarship: Neuroprotection through 2006 – 2009 $68,500 cell cycle inhibition in acute ischaemic stroke 2007 – 2009 $31,422

72 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Kumar S Roles of Ndfip1 and Ndfip2 as adaptors for the Nedd4 family of Parker M, Hercus T Studies of proteins involved in cancer and allergic ubiquitin ligases diseases 2008 – 2010 $200,000 2006 – 2008 $166,250 Kumar S, Cook D Physiological function of Nedd4-2 in regulating the Parsons D, Anson D, Siu K, Kuchel T, Smith G Correction and epithelial sodium channel measurement of the basic defects in cystic fibrosis 2008 – 2010 $257,750 2007 – 2009 $298,000 Kumar S Caspase function in animal development Pitson S The role of SKAM and sphingosine kinase in wound healing 2006 – 2009 $169,128 2008 – 2010 $90,000 Kumar S Senior Principal NHMRC Fellowship Pitson S Research Fellowship 2006 – 2010 $147,250 2008 – 2012 $107,500 Kumar S Caspase-2 function in cell death and disease Pitson S The molecular mechanisms regulating oncogenic signalling by 2007 – 2009 $172,900 sphingosine kinase 1 phosphorylation and localisation Kumar S, Cakouros D Transcriptional control of programmed cell death 2007 – 2009 $151,850 2006 – 2008 $169,681 Powell B, Anderson P, Zannettino A, Gronthos S, David D Lau D Training Postgraduate Scholarship: Relationship between changes Mechanisms of premature cranial fusion: role of retinol binding protein 4 in due to cardiac thickening and increased heart rhythm disorders osteogenesis and suture fusion 2008 $31,422 2008 – 2010 $178,000 Leong D NHMRC/NHF Training Postgraduate Scholarship: The integrated Psaltis P (Co-funded with National Heart Foundation) Medical Postgraduate assessment of cardiac function and synchrony, and its clinical implications Scholarship: A study of the properties of STRO-1 selected mesenchymal in cardiac pacing stem cells and their potential for cardiac repair 2008 – 2010 $31,422 2006 – 2008 $31,422 Liew G Training Postgraduate Scholarship: Investigation of diseased blood Ratcliff RM, Higgins GD, Davidson GP, Arthur JL A new virus vessels that can cause strokes using the latest scanning technologies causing acute gastroenteritis in humans 2008 – 2009 $32,003 2008 – 2010 $172,750 McColl S Understanding the mechanism and significance of CXCL16- Rayner C, Fraser R, Horowitz M, Wittert G, Feinle-Bisset C, medicated protection of tumour cells from CTL-induced apoptosis Jones K, Clifton P Equipment grant: Equipment for concurrent impedance, 2006 – 2008 $171,250 manometry and barostat recordings in nutritional physiology studies 2008 $52,000 McColl S Studies on the role of the p101 component of the Class 1B PI 3- kinase in cell migration and activation Reynolds P, Reynolds A Improved gene delivery strategies for primary 2006 – 2008 $149,250 pulmonary hypertension 2006 – 2008 $123,556 McColl S, Kochetkova M, Hoffmann P Understanding the function of the CCR7 chemokine receptor in breast cancer cells and tumours Reynolds P Practitioner Fellowship 2007 – 2009 $160,150 March 2007 – February 2012 $80,850 McFarlane A, Galletly C, Sim M, Sawyer M, Baghurst P Childhood Reynolds P, Holmes M, Hodge G, Hodge S, Chambers D cognitive antecedents of adult psychopathology: follow-up of the Port Pirie Monitoring of cytokine/chemokines to improve morbidity and rejection rates Lead Cohort into adulthood in lung transplant patients 2007 – 2009 $188,550 2008 – 2010 $119,650 Mathias J, Bigler E, Bowden S, Rosenfeld J, Taylor D, Vink R, Robertson S Macrophage-regulated tissue remodelling in endometrial Rose S Diagnostic and prognostic evaluation of diffusion tensor imaging receptivity ofr embryo implantation and pregnancy success and cognitive function after traumatic brain injury 2006 – 2008 $160,250 2008 – 2010 $279,750 Robinson BWS, Reynolds PN, Currie A, van der Most R, Lake R, Molaee P NHMRC/NHF Training Postgraduate Scholarship: Assessing Nowak A, Scott B National Asbestos Diseases Research Institute Project: heart function using magnetic resonance imaging Integrating conventional mesothelioma therapies with immuno- and 2008 – 2009 $32,003 gene-therapies 2007 – 2009 $208,205 Morris H, O’Loughlin P, May B Maintenance of bone strength in aged rats: the vitamin D requirement Russell D, Ricciardelli C, Williams E Mechanism of breast cancer 2007 – 2009 $177,350 metastasis: tumour cell remodelling of the extracellular matrix 2008 – 2010 $120,733 Newcombe R Training Postgraduate Scholarship: Mechanisms of cell death in chronic spinal cord compression using a rat model Saint R, Kumar S, Richardson H, Richards R, Hime G, O’Neill S 2008 – 2010 $31,422 Enabling Grant: Australian Drosophila biomedical research support facility 2007 – 2011 $200,000 Norman R, Hickey T, Tilley W Androgen receptor activity in normal and abnormal human ovarian function Sanders P Stretch induced pulmonary vein remodelling: implications for 2007 – 2009 $133,375 the initiation and maintenance of atrial fibrillation 2006 – 2008 $184,750 Norman RJ, Rodgers RJ, Robertson SA, Thompson JG, Lane M, Davies MJ, Dekker GA, Irving-Rodgers HF, Jasper MJ, Hayball Scott H Senior Research Fellowship Level B JD, Gilchrist RB, Kind KL, Moore VM, Willson K, Chan A 2007 – 2011 $119,000 Periconceptual foundations for a healthy start to life Scott H, Heath WR et al Program Grant for European Collaboration: 2007 – 2008 $36,000 Novel Approaches to pathogenesis, diagnosis & treatment of autoimmune Omari T, Blackshaw LA Neuromodulation of triggering of transient lower diseases based on new insights into thymus-dependent self-tolerance oesophageal sphincter relation and gastro-oesophageal reflux 2004 – 2008 $199,128 2008 – 2010 $118,292 Goodnow C, Scott H et al Program Grant for European Collaboration: Autoimmune polyendocrine syndrome type I – a rare disorder of childhood as a model for autoimmunity 2006 – 2008 $100,164 73 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Slade G, Spencer J, Roberts-Thomson K, Hiller JE. Capacity Leung M ‘J’ Trust Fund: Impaired microvascular perfusion immediately after Building Grant: Oral health research for the Australian population primary percutaneous coronary intervention as a predictor of adverse 2005 – 2009 $498,650 myocardial infarction characteristics on cardiac MRI Stringer A Biomedical PhD Scholarship: Chemotherapy-induced mucositis: 2008 $10,000 the role of gastrointestinal microflora and mucins in the luminal environment Reynolds P 2008 – 2009 $21,866 Mechanisms underlying the link between endothelial BMPR2 gene Thomas D Medical Postgraduate Scholarship: Survival signalling in acute expression and pulmonary hypertension myeloid leukaemia 2008 – 2009 $63,000 2007 – 2009 $31,422 Sanders P, Young GD, Mackenzie L Thompson PD, jointly with Semmler JG, Nordstrom MA, Pitcher Role of the coronary sinus musculature in the substrate for atrial fibrillation JB, Todd G, Ridding MC Equipment grant: Neuromotor Training and 2007 – 2008 $60,927 Rehabilitation Facility (University of Adelaide) Worthley SG, Wittert GA, Worthley MI Cardiovascular and 2008 $38,000 inflammatory effects of dietary intervention in obesity Tilley W, Butler L, Marshall V Androgen receptor signalling in 2008 – 2009 $64,500 development and progression of prostate cancer Young G, James M, Metcalf R, Sanders P Effects of both dietary and 2007 – 2009 $241,250 acute administration of n-3 polyunsaturated fatty acids on cardiac Tilley W, Owens J, Norman R, Findlay D, Keefe D, Wittert G et al electrophysiology in humans Equipment grant: Distiller image analysis software and server 2008 – 2009 $61,120 2008 $52,000 National Institutes of Health USA Turner R Postgraduate Overseas Biomedical Fellowship Chisari F, Wieland S, Purcell R, Jilbert AR Pathogenesis of liver 2008 – 2012 $62,000 disease in hepatitis Vadas MA, Lopez AF, Gamble JR, Goodall GJ Program Grant: 2008 $34,625 USD (subcontractor funding only) Leucocyte and endothelial cell biology Lanford RE, Mason WS, Jilbert AR Resolution of acute hepatitis B virus 2005 – 2009 $926,993 infections in chimpanzees Vink R, Blumbergs P, Fadan A Substance P antagonists as a novel 2007 – 2008 $39,960, $49,796 USD (subcontractor funding only) therapeutic intervention in stroke Mason WS, Jilbert AR Hepadnavirus infections and liver cancer 2006 – 2008 $103,750 June 2005 – May 2010 $28,517 USD (subcontractor funding only) Vink R, Blumbergs P, Van Den Heuvel C Raised intracranial pressure Neil Sachse Foundation after trauma: characterisation and development of pharmacological Vink R Equipment Grant: Nova free magnesium analyser interventions 2008 $25,000 2008 – 2010 $189,000 Vink R Characterising cell death following spinal cord injury Wake M, Gunn J, Gibbson K, Wittert G, Gold L General Practice 2008 $40,000 Clinical Research Program: Better outcomes for obese children in general Nobel Biocare practice: randomised control trial of a new shared-care-model vs usual care 2008 – 2010 $160,000 Fazzalari N Influence of surface roughness and shape on microdamage of the osseous surface adjacent to osseointegrated dental implants during Watson D, Jamieson G, Martin C, Smith G Randomised trials for implant placement antireflux surgery 2008 – 2009 $45,000 2006 – 2010 $197,887 Northern Communities Health Foundation Wetzig N, Campbell I, Gill G, Ung O, Collins J, Bilous M, Hague W, Kirby A SNAC2: A randomised trial of extending sentinel node based Worthley S Relationship between electro-anatomic and functional management to women with larger or multifocal breast cancers characteristics in patients with atrial abnormalities using magnetic resonance 2008 – 2010 $395,071 imaging (MRI): implications for stroke risk 2008 – 2010 $15,000 Wittert G Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes – a randomised trial Novartis Pharmaceuticals 2008 – 2011 $488,875 Hughes C TWISTER study: A phase II study of withdrawal of imatinib Woodcock J Regulation of 14-3-3 monomerization controls cell therapy in adult patients with chronic phase myeloid leukaemia in stable life/death fate complete molecular remission 2006 – 2008 $174,878 18/6/2008 – 30/6/2011 $67,773 Yeoh A Biomedical Postgraduate Scholarship: Radiation-induced Hughes TP, Ross D Correlative studies linked to Twister (CML8) study mucositits: relationships between short and long-term fractionated radiation, 2007 – 2009 $163,133 NF-kappaB, COX-1, and COX-2 Hughes TP, White DL Correlative studies linked to TOPS (CSTIK2301) 2007 – 2008 $11,129 clinical trial Zannettino ACW, Gronthos S, Peet DJ, To L, Evdokiou A The role of 2006 – 2008 $195,453 CXCL12(SDF-1)/CXCR4 in pathological angiogenesis and osteolytic bone Hughes TP, White DL Corrleative studies linked to TIDEL II (CML9) study disease of multiple myeloma 2007 – 2009 $594,736 2007 – 2009 $217,400 Singhal N, Brown MP Phase II study evaluating efficacy and safety of National Heart Foundation Everolimus with Letrozole for management of advanced (unresectable or Gentilcore D Clinical Postdoctoral Research Fellowship Award: metastatic) non small cell lung cancer after failure of platinum-based Pathophysiology of postprandial hypotension in the elderly – role of gastric treatment and small intestinal mechanisms 2007 – 2008 $209,920 2008 – 2009 $64,750

74 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Singhal N, Brown MP A parallel phase I study of LBH589 in combination Rebecca L Cooper Medical Research Foundation with external beam radiotherapy or chemoradiation for locally advanced non Horowitz M, Jones KL, Gentilcore D, Rayner CK, Feinle-Bisset C small cell lung cancer CLBH589CAU02T Measurement of autonomic nerve function in patients with diabetes with or 2007 – 2009 $256,000 without postprandial hypotension Zannettino A, Dewar A, To LB, Hughes TP Tyrosine kinase inhibition 2008 $20,000 as a potential modality to control osteolytic bone disease: a new role for Proudman S Genetic risk factors for cardiovascular disease in rheumatoid Imatinib mesylate and second generation Bcr-Abl inhibitors arthritis 2007 – 2010 $157, 000 2008 $20,000 Novartis Pharmaceuticals and Bristol Meyer Squibb Replicor Inc Hughes TP RESIST study Jilbert AR. Section IV. Second in vivo experiment. To study the ability of 2008 – 2009 $850,000 PS-ON REP AC to inhibit DHBV infection in vivo in 14-day old ducklings. Novartis Pharmaceuticals Australia Pty Ltd Hughes T Substudy No March 2007 – October 2008 $18,642 2 (Pilot study of DNA PCR monitoring) of the CML9 TIDEL II Jilbert AR. Section VI. Third in vivo experiment. Dose response experiment 2008 $67,647 of the ability of REP 9AC (REP 2055) to inhibit DHBV infection in vivo in Novo Nordisk Pharmaceuticals Pty Ltd 14-day old ducklings. Davidson R The effect of weight loss and dietary modification on cardiac August 2007 – October 2008 $19,377 and vascular abnormalities in type 2 diabetes mellitus: A serial non-invasive Jilbert AR. Section VII. Fourth in vivo experiment to test prophylactic and study using cardiac magnetic resonance (CMR) and echocardiographic therapeutic treatment of 14-day old DHBV infected ducklings with the endpoints REPLICor PS-ON, REP 9AC (REP 2055). 2008 $4,000 October 2007 – November 2008. $56,016 Torpy D Regional Diabetes Scheme: Screening on Cushing’s syndrome and Royal Adelaide Hospital/SA Pathology Research Committee primary aldosteronism in Type 2 diabetes mellitus Ahern J Mannose binding lectin – a potential therapy for improving alveolar 2008 $4,000 macrophage function in chronic obstructive pulmonary disease Oncaidia Ltd (COPD)/emphysema? Brown M Apomab and telomerase technology – Consultancy Agreement 2008 $20,000 July 2007 – June 2008 $30,000 Alasady M Dawes Postgraduate Scholarship (top-up): Atrial Ophthalmic Research Institute of Australia (ORIA) arrhythmogenesis as a consequence of myocardial ischemia 2008 – 2010 $5,000 Chidlow G, Casson RJ Further aspects of osteopontin in the retina 2008 $48,250 Alsharifi M Early Career Fellowship: Identifying elements of the immune responses responsible for cross-protection during viral infections, induced Ovarian Cancer Research Foundation by gamma ray inactivated viruses and peptide-based vaccines Oehler MK, Hoffmann P Proteomics of ovarian cancer implantation 2008 – 2010 $71,060 2008 $40,000 Blackshaw LA, Horowitz M, Page A, Rayner C Bridging Grant: Oehler MK, Hoffmann P Autoantibodies in ovarian cancer Adaptation of nutrient sensing from the gut in response to diet and disease 2008 $24,000 2008 $50,000 Pfizer Bonder C Uremic serum causes endothelial progenitor cell dysfunction Leung M Cardiovascular Lipid Research Grant: Impaired microvascular 2008 $20,000 perfusion immediately after primary percutaneous coronary intervention as Bonder C Mary Overton: Leukocyte trafficking in disease: a role for a predictor of adverse myocardial infarction characteristics on cardiac MRI sphingosine kinase 2008 $30,000 5/9/2007 – 31/12/2008 $50,000 Soon K, Worthley SG, Brown M Cardiovascular Lipid Research Grant: Brooks A High density mapping of atrial fibrillation – organisation within Direct comparison between magnetic resonance imaging and multi-slice chaos? computed tomography in the evaluation of coronary artery disease 2008 – 2010 $20,000 2008 $50,000 Butler L Florey Fellowship: The role of androgen receptor signalling in the Worthley MI, Nelson A, Worthley SG Cardiovascular Lipid Research normal human breast Grant: Assessment of coronary endothelial function using cardiac magnetic 2006 – 2008 $88,060 resonance imaging Butler M Dawes Postgraduate Scholarship (top-up): Non-genomic 2008 $47,3315 androgen receptor signalling and its potential role in contributing to Premier’s Science & Research Fund anovulation in women with polycystic ovary syndrome Wittert G, Hiller J, Andrews G, Taylor A, Tilley W, Buchanan G, 2008 – 2010 $5,000 Marshall V, Ivell R, O’Loughlin P, Warin M, Braunack-Mayer A, Cawrse J Dawes Postgraduate Scholarship (top-up): Role and function of Burns N, Nettelbeck E, Wilson C, Fenech M, Findlay D, Fazzalari ANKRD11 in tumourigenesis N, Casson R The Florey Adelaide Male Ageing Study: Promoting health 2008 – 2010 $5,000 wellbeing and utilisation of health services by middle aged and older men Cleland L, McColl SR, Hoffmann P Characterisation of citrullinated 2006 – 2008 $300,000 peptides in rheumatoid synovial fluid and removal by synovial lavage Prostate Cancer Foundation of Australia 2008 $10,000 Buchanan G, Koff A, Hakim D, Coetzee G A novel regulator of Deane A, Bryant L, McConnell H, Chapman M, Holloway R, androgen receptor function in prostate cancer Fraser R The effects of intravenous sedation on the lower oesophageal 2008 – 2012 $146,719.80; $120,282; $123,238; $123,238 sphincter: a comparison between dexmedetomidine and propofol in humans 2008 $21,274

75 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Eyre N The involvement of PDZK1 in SR-B1-dependant entry of Hepatitis Thomas D Validation of a novel cytokine gene signature as a prognostic C virus marker in acute myeloid leukaemia 2008 $20,000 2008 $24,000 Feinle-Bisset C, Horowitz M, Jones KL Characterisation of day-to-day Thompson S Prognostic factors in oesophageal cancer – the importance of variations in energy intake in healthy men and women, and the effect of the malignant cells in lymph nodes menstrual cycle in women – relationships with gastric emptying, intragastric 2008 $21,712 meal distribution and gastrointestinal and reproductive hormones Willoughby S The impact of restoration of sinus rhythm on endothelial 2008 $15,000 function and inflammation Gentilcore D, Jones K, Horowitz M, Rayner C Effects of the 2008 $10,000 oligosaccharide, alpha-cyclodextrin, on postprandial blood pressure in Young RL, Rayner C, Blackshaw LA, Horowitz M Intestinal taste healthy older subjects – relationships to gastric emptying, glycaemia and receptor molecules in human type-2 diabetes superior mesenteric blood flow 2008 $24,225 2008 $15,000 Royal Adelaide Hospital/SA Pathology Research Grimbaldeston M Mary Overton Project: Leukocyte trafficking in disease: Committee/University of Adelaide a role for sphingosine kinase Barratt D Dawes Postgraduate Scholarship: Role of drug transporters in the 2008 $50,000 clinical pharmacology of opioids Hahn C Bridging grant: Funiwasectional in vivo screen angiogenic genes April 2005 – April 2008 $9,418 and analysis of selected critical genes in angiogenesis and tumours Brennan I Dawes Scholarship: Evaluation of appetite regulation in the lean 2008 $50,000 and obese subjects Harvey N Florey Fellowship: The identification and characterisation of March 2006 – February 2009 $21,226 lymphangiogenic genes in health and disease Curry E Dawes Postgraduate Scholarship (top-up): Correlating target 2005 – 2009 $99,986 antigen responses with vector-specific immunity following immunisation with Hiwase S Characterisation of mesenchymal stromal cells from placenta and recombinant fowlpox virus its role in umbilical cord blood transplantation 2007 – 2009 $5,000 2007 – 2008 $21,866 Deane A Gastrointestinal dysmotility underlying difficulties with nutrition, Hodge S Florey Fellowship: Investigating the causes of failed efferocytosis metabolism and recovery in critical illness in COPD/emphysema with a view to identifying novel therapeutic targets 2007 – 2009 $20,489 2008 – 2010 $99,986 Forsyth J Dawes Postgraduate Scholarship (top-up): Structural and Howie D Polyethylene wear and migration of acetabular components functional analysis of a novel centrosome associated protein, Nedd1 following total hip replacements with a large articulation 2006 – 2009 $5,000 2008 $20,000 Gordon E Dawes Postgraduate Scholarship (top-up): Investigating the role Kong Y Dawes Scholarship: Growth factors and neurogenesis and mechanism of action of macrophages in embryonic lymphangiogenesis 2008 – 2010 $20,007 2007 – 2009 $5,000 Leong D Dawes Postgraduate Scholarship (top-up): The integrated Hewett D Florey Fellowship: Functional analysis of candidate genes assessment of cardiac function and synchrony, and its clinical implications implicated in 5q- syndrome and haematopoiesis in cardiac pacing 2007 – 2009 $87,240 2008 – 2010 $5,000 Hiwase D Dawes Postgraduate Medical Scholarship: Evaluation of anti- Limaye V A South Australian database for patients with biopsy-proven proliferative and pro-apoptotic effect of dasatinib on CML CD 34+ cells inflammatory myositis 2006 – 2009 $30,600 2008 $25,000 Jarman K Dawes Postgraduate Scholarship (top-up): Mechanisms Menicanin D Dawes Scholarship: Characterisation of the cellular mediating the functional activation of sphingosine kinase and its cellular differentiation hierarchy of stromal tissues consequences 2008 – 2010 $20,007 2006 – 2009 $5,000 Molaee P Assessment of left atrial function using electro-anatomic Kleinig T Dawes Postgraduate Scholarship (top-up): Neuroprotection mapping and cardiac magnetic resonance imaging through cell cycle inhibition in acute ischaemic stroke 2008 $20,000 2007 – 2009 $5,000 Oehler MK, Hoffmann P, Ricciardelli C, Brown MP Profiling of the Lee M Targeting the vicious cycle of cancer induced bone disease with immunoproteome in early ovarian cancer novel therapeutics 2008 $21,600 2007 – 2009 $10,933 Peh CA Establsihment of an ANCA positive vasculitis clinical sample Lee M Dawes Scholarship: The minimal vitamin D requirement relative to repository at the RAH/Hanson Institute calcium intake for the maintenance of bone micro-architecture in aged rat 2008 $6,400 2007 – 2009 $10,933 Ruszkiewicz A Survival and response to adjuvant chemotherapy in Dukes’ Paterson E Dawes Scholarship: Regulation of mRNA turnover c serrated pathway adenocarcinoma of the colorectum February 2006 – January 2009 $21,231 2008 $20,000 Psaltis P Dawes Postgraduate Scholarship (top-up): A study of the Stringer A Dawes Scholarship: Toxicity of chemotherapy agents properties of STRO-1 selected mesenchymal stem cells and their potential for 1/2/2006 – 31/1/2009 $21,231 cardiac repair Thomas D Comparison of effects of calcium and vitamin D separately and 2006 – 2009 $5,000 in combination of serum pth and bone resorption markers in elderly women Stiles M Dawes Postgraduate Medical Scholarship: Electrophysiological 2008 $14,136 and electroanatomical remodeling of the ateria in patients with atrial flutter 2006 – 2009 $30,600

76 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

Tang C Dawes Postgraduate Scholarship: Determining the role of Susan G Komen For the Cure intracellular uptake and retention of Abl kinase inhibitors in leukaemic stem Butler LM, Tilley WD, Birrell SN The role of androgen receptor cells and progenitors in CML signaling in the breast: potential disruption by synthetic progestins used in 2008 – 2010 $10,933 hormone replacement therapy Thomas SDC, Need AG, Slobodian P, Nordin BEC Comparison of the July 2005 – June 2008 $41,999 effects of two marketed calcium preparations on bone resorption in Tilley WD, Roder DM, Raymond WA, Birrell SN, Bianco-Miotto T postmenopausal women Androgen receptor status as a determinant of breast cancer risk and disease January 2007 – June 2008 $5,700 progression Vakaci I Dawes Postgraduate Scholarship: Differentially loaded 2006 – 2008 $88,014 radiostereometric analysis (RSA) for fracture assessment The Cancer Council South Australia 2008 – 2010 $10,933 Butler L Senior Research Fellowship: Androgen signalling in the normal Wyatt L Dawes Postgraduate Scholarship (top-up): Investigating the human breast: role and implications for breast cancer risk regulation of tyrosine phosphatase Pez-mediated signalling in embryonic 2008 – 2011 $98,000 development and human disease Callen D, Sharma R, Farshid G The role of FBXO31 in a novel pathway 2006 – 2009 $5,000 of breast tumour suppression Young J Dawes Scholarship: Structure function studies of novel genes 2008 $107,724 involved in blood vessel formation Dorstyn L Analysis of the mechanisms of caspase regulation in Drosphila June 2006 – June 2009 $21,231 2008 $88,500 Royal Australasian College of Physicians Gibson R Post-doctoral Research Fellowship: Gene profile changes in Gagliardi L Novartis Oncology Endocrinology Fellowship: Adrena human oral mucosa following treatment with cytotoxic agents Cushing’s endocrine and genetic pathogenesis and prevalence in high-risk April 2004 – May 2009 $34,000 groups Goodall G mRNA targets of microRNAs involved in metastasis 2008 $40,000 2007 – 2008 $77,250 Leung M, Worthley SG Post Doctoral Fellowship: Servier Staff Research Goodall G Fund 50% of Microarray Research Associate at the Adelaide Fellowship: Assessment of microvascular perfusion in patient presenting with Microarray Facility STEM January 2007 – June 2009 $43,333 2008 $10,000 Griesser HJ, Thierry BJ, Brown MP, Majewski P, Taylor J An Rural Industries Research and Development integrated approach to the development of advanced functional Heuzenroeder M Expansion and refinement of a molecular typing system nanostructures as cancer diagnostic and therapeutic agents for Salmonella 2007 – 2008 $ 71,000 July 2006 – June 2010 $94,880 Guthridge M Peter Nelson Leukaemia Senior Research Fellowship: The role San Remo of a novel GM-CSF signalling pathway in regulating cell survival in Myeloid Callen D San Remo Fellowship: Novel tumour suppressors define new Leukaemia molecular pathways of tumourigenesis August 2005 – July 2008 $88,160 2007 – 2009 $100,000 Guthridge M A novel cytokine-receptor survival axis in chronic myeloid Neilsen P Fellowship leukaemia 2007 – 2009 $86,000 2008 $100,000 Scoliosis Research Society Hahn C The role of a novel protein, VasGAP, in angiogenesis Briggs AM, Parkinson I, Wark JD, Fazzalari NL Scoliosis 2007 – 2008 $77,250 Research Society Measurement of vertebral subregional bone mineral Hardingham J, Chataway T, Hewett P Development of new biomarkers density using lateral-projection DXA: Establishing concurrent and predictive for micro-metastatic disease detection in early stage colorectal cancer validity. 2008 $82,750 2008 – 2009 $14,875 Khew-Goodall Y Cancer Council Senior Research Fellowship: the role of Sir Edward Dunlop Medical Research Foundation tyrosine phosphatase PEZ in cancer progession Willoughby S Reducing the risk of stroke following cardioversion: July 2006 – June 2009 $89,964 Characterisation of the effect of restoration of sinus rhythm on endothelial Khew-Goodall Y Regulation of epithelial-mesenchymal transition in cancer function and inflammation in men 2008 $75,250 1/7/2008 – 30/6/2009 $7,500 Kumar S Nedd1 function in centrosome, cell cycle and senescence Smith & Nephew Inc 2008 $83,500 Fazzalari N Evaluation of poly lactide carbonate in poor quality bone Ramshaw H Peter Nelson Leukaemia Senior Research Fellowship: June 2006 – January 2008 $20,410 Development of a non-toxic therapy for AMC (acute myeloid leukaemia) Stem Cell Healthcare & Tech Inc April 2008 – April 2011 $92,000 Barry SC, D’Andrea RJ, Lewis ID Cord blood stem cell expansion Reynolds P Combined oncolytic and immuno-therapy for mesothelioma 2008 $92,000 2008 $85,000 Stryker Australia Pty Ltd TQEH Research Foundation Chehade MJ, Solomon LB, Pohl AP, Howie DW, Carbone T, D’Andrea RJ, Brown AL, Lewis ID KLF5 function in normal and Taylor A Health outcomes of patients with fractures of the hip according to leukemic myelopoiesis fracture type, treatment and patient preinjury mobility 2008 $98,000 2008 – 2009 $60,000 Tyco Healthcare Pty Ltd Ruszkiewicz A Research Assistant support for Colorectal Unit 2007 – 2008 $40,000

77 Annual Report 2008 Hanson Institute Proudly bringing together the best CURRENT GRANTS of South Australia’s medical research

University of Adelaide Al-Dasooqi N Australian Postgraduate Award: Matrix metalloproteinases: key regulators of chemotherapy-induced mucosal injury 2008 – 2010 $26,669 Anderson P Early Career Research Fellowship, Faculty of Health Sciences 2007 – 2009 $70,000 John B Biosense-Webster Electrophysiology Scholarship 2006 – 2008 $30,000 Ricciardelli C Hilda Farmer Fellowship: Versican as a target to inhibit peritoneal adhesion of ovarian cancer cells 2007 – 2009 $105,000 Wigg A Patient Partner Teaching Program March 2008 $7,200 University of Adelaide/CSIRO Danthiir V, Wilson C, Nettelbeck T, Burns N, Wittert G Brailsford Robertson Award: Impact of nutrition, including long-chain Omega-3 polyunsaturated fatty acids on cognition and functional ageing 2007 – 2008 $100,000 University of Adelaide Faculty of Health Sciences Hiller JE, Elshaug AG University of Adelaide Faculty of Health Sciences Research Committee, Research Development Award: Implementing and evaluating a framework to disinvest ineffective health care 2008 $13,000 Hiller JE, Gericke CG University of Adelaide Faculty of Health Sciences Research Centre (Adelaide Centre for Health Technologies and Services Research – ACTS) 2008 $40,000 University of Adelaide Research Committee Wittert G Healthy Ageing Research Cluster (HARC) 2008 $100,000 University of Queensland Kuchel T Large Animal Imaging Facility (LARIF) October 2007 – September 2012 $867,000 US Army Medical Research and Materiel Command Barrett J Prostate Cancer Training Award: Role of Apha-SGT in hormone regulated prostate cancer cell growth 2008 – 2010 $129,826 Kennaway D, Tilley WD, Butler LM Disruption of the circadian rhythms of gene expression and the development of breast cancer 2006 – 2009 $173,333 Tilley WD, Butler LM, Marshall VR Mechanism of prostate cancer tumorigenesis 2007 – 2010 $147,889 Victorian Neurotrauma Initiative Tan S-S, Kumar S, Vaux D, Morganti-Kossmann C, Silke J, Kossmann T (Howard Florey, LaTrobe University and Alfred Hospital) Preventing neuronal cell death following brain trauma 2007 – 2009 $553,333 Virax Holdings Ltd Hayball JD, Brown MP, Howley PM Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors 2005 $12,500; 2006 $25,000; 2007 $25,000; 2008 $12,500

78 Annual Report 2008 Hanson Institute Proudly bringing together the best PATENTS of South Australia’s medical research

Hanson Institute Patents

08

07

06

05

04

0 1020304050 Number of Patents

Commercial Development L>R Elena Voss, Bernadette Swart, Craig Rogers, Liz Holland-Clarke, Daniela Tyson, The role of the Intellectual Property & Commercialisation (IP&C) Dara Melanson Office is to facilitate links with industry, government and other research organisations through the provision of contract Research, Consultancy, and Services Agreements together with IP&C Office staff commercialisation of IP. Bernadette Swart IP & Commercialisation Manager The formation of SA Pathology in July 2008, which now includes sites at the Women’s and Children’s Hospital and Flinders Elizabeth Holland-Clarke Medical Centre resulted in a significant increase in the IP&C Senior Commercial Lawyer Office portfolio. Belinda Wade Business Development Associate Patent Update Craig Rogers The granting of patents provides international recognition of Business Development Associate innovative research conducted at the Hanson Institute, incorporating research from SA Pathology and the Royal Adelaide Daniela Tyson Hospital (RAH). Currently the IP&C Office has 144 filed patents Intellectual Property Officer awaiting examination and holds 44 granted patents under Dara Melanson commercial development. Intellectual Property Officer Elena Voss In 2008 the following patents held by Medvet Science on behalf of the Intellectual Property Administration Officer (part-time) Hanson Institute, IMVS (now part of SA Pathology) and RAH were granted. Contact (08) 8222 3839 Inventors: Lopez A, D’Andrea R. www.medvet.com.au Title: Method of Modulating Leukemic Cell and Eosinophil Activity with Linking Science to Markets Monoclonal Antibodies Country: USA Patent 7,427,401 Inventors: Gamble J, Vadas M, Li X Title: A method of modulating endothelial cell activity Country: Australia Country: Australia Patent 2003258356 Inventors: Heuzenroeder M, Barton, Vanniasinkam T Title: GroEL Chimeric Protein and Vaccine Country: New Zealand Patent 532070 Agreement Update The IP&C office reviewed and administered 439 new agreements which included the negotiation and execution of 32 research and licence agreements. Highlights included: the signing of an agreement with CSL Ltd to develop a treatment for leukaemia and inflammatory diseases by targeting a protein that has been found to be deregulated in certain clinical conditions. The findings were published in Cell in August and are the result of a collaboration between researchers at the Hanson Institute and St Vincent’s Institute in Melbourne. The partnership with CSL will see the development of antibodies to the protein receptor.

79 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH ETHICS of South Australia’s medical research

The Research Ethics Committee and the Investigational Drugs Subcommittee provide a critical component of the infrastructure for human research activities at the Hanson Institute. The year 2008 saw 291 new studies approved. Of these, 109 were clinical drug trials where the most numerous group were cancer trials, representing >25% of the total drug trials. Of the non-drug trials, the discipline with the highest number was Cardiology, representing 12% of the total. With overlap from previous years, more than 1000 projects are active at any time. The Research Ethics Committee meets National Health and Medical Research Council (NHMRC) Guidelines, which aim to provide a broad mix of experience and viewpoints. The Committee currently includes: • A Minister of Religion • A Layman • A Laywoman • A Lawyer • A Doctor • A Clinical Psychologist • A Scientist • Seven physicians from a range of medical specialties A variety of research projects are assessed and these include clinical drug trials, physiological studies on human subjects who might be patients or healthy volunteers, laboratory-based studies with human material such as blood cells and tissue samples and qualitative research studies. For clinical drug trials where a new or existing drug is being examined outside of its approved indication, the research proposal is subjected to an additional level of analysis provided by the Investigational Drugs Subcommittee. This committee, which has in its membership clinical pharmacologists, the Director of the RAH Pharmacy, and a research pharmacist, reviews the protocols from a viewpoint of drug safety, regulatory requirements, and the general study design. The subcommittee makes recommendations to the Research Ethics Committee which also reviews the same protocols. The reviews and the level of documentation maintained by the Research Ethics Committee allow drug trials in this centre to meet the highest international standards of conduct which are required by government regulatory authorities. Dr Michael James Chairman Research Ethics Committee

80 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL STUDIES of South Australia’s medical research

Clinical studies enable us to identify and evaluate safer and more Casson R Micropulse laser treatment of diabetic macular – pilot study with effective medical treatments and are an important component of 2RTV1 prototype. the activities of the Hanson Institute. Casson R A 12 month phase 2, single centre, proof of concept trial to Clinicians of the Hanson Institute are actively involved in many assess the safety and efficacy of the micropulse laser in the treatment of local, national and international studies trialling a range of new proliferative diabetic retinopathy. The Proliferative Diabetic Laser Trial. drugs, medical devices and treatment programs. Chapman M A randomized, double-blind, placebo-controlled, multicenter, Key phase-3 study of Drotrecogin Alfa (activated) administered as a continuous Investigator 96-hour infusion to adult patients with septic shock. F1K-MC-EVDP Study Title PROWESS Chatterton B An open-label, non-randomized, multi-center study to Andrews J Effect of the probiotic bacterium Escherichia coli Nissle 1917 on optimize image assessment and evaluate the efficacy and safety of BAY 94- symptom pattern and immunologic function in patients suffering from 9172 (ZK 6013443) positron emission tomography (PET) for irritable bowel syndrome with diarrhoea. detection/exclusion of cerebral amyloid beta in patients with probable Antic R RESTORA 1 – Multi-center, double-blind, randomized, placebo- Alzheimer’s disease compared to healthy volunteers. Protocol 311741 controlled, active reference, parallel-group polysomnography study to assess Chong C Efficacy of screening ultrasound in hepatocellular carcinoma. the efficacy and safety of a 16-day oral administration of ACT-078573 in adult subjects with chronic primary insomnia. Collins M Screening for colorectal cancer in kidney transplant recipients. CRCKT01A Bannister K A 12-week, open label, multicenter, titration study with a 9- month maintenance treatment extension, to demonstrate efficacy of SBR759 Coventry B A phase 2 study of intralesional PV-10 in the treatment of compared to sevelamer HCl in lowering serum phosphate levels in chronic metastatic melanoma. PV-10-MM-02 kidney disease patients on hemodialysis. CSBR75 Deane A The effects of intravenous sedation on the lower oesophageal Bradley J A comparison of prasugrel and clopidogrel in acute coronary sphincter: a comparison between dexmedetomidine and propofol in humans. syndrome (ACS) subjects with unstable angina/non-ST-elevation myocardial Dimitri H Acute atrial electrical remodelling in response to obstructive sleep infarction (UA/NSTEMI) who are medically managed. H7T-MC-TABY apnoea episodes. TRILOGY ACS Dundon B Evaluation of alterations in cardiovascular structure and function Briffa M A double-blind, dose-ranging study to determine the optimal oral following surgical arterio-venous fistula closure after successful renal morphine or oxycodone needed to treat breakthrough pain for people on transplantation. regular opioid in the palliative care setting. (Breakthrough Opioid Study) Elias T A randomised, controlled trial of exit site application of Medihoney BT06 antibacterial wound gel for the prevention of catheter-associated infections in Briffa M A randomized, double-blind, placebo-controlled study of a fixed peritoneal dialysis patients. HONEYPOT dose of subcutaneous methylnaltrexone in adults with advanced illness and Faull R A phase 2 randomised, multicentre, active comparator-controlled opioid-induced constipation: Efficacy, Safety, and Additional Health trial to evaluate the safety and efficacy of CP-690,550 and mycophenolate Outcomes. 3200K1-4000-WW mofetil/ mycophenolate sodium in de novo kidney allograft recipients. Briffa M Open label extension study to assess the safety of a fixed dose of A3921030 subcutaneous methylnaltrexone in subjects with advanced illness and Faull R A randomized, controlled, open-label, multi-centre, parallel-group opioid-induced constipation. 200K1-4001-WW study to assess all-cause mortality and cardiovascular morbidity in patients Brooks A Efficacy of coronary sinus ablations for treatment of atrial with chronic kidney disease on dialysis and those not on renal replacement fibrillation. therapy under treatment with MIRCER. Brooks A Repolarisation variability during fixed pacing. Faull R A randomised, double blind, placebo-controlled parallel study to Brooks A Effect of rate and structure on complex fractionated atrial assess the efficacy and safety of L-carnitine for the treatment of dialysis- electrograms as a substrate for atrial fibrillation. related disorders in end-stage renal disease patients undergoing long-term haemodialysis treatment. LC/08.06 Brown M A parallel phase I study of LBH589 in combination with external beam radiotherapy or chemoradiation for locally advanced non small cell Gagliardi L Adrenal Cushing’s: natural history and genetic analysis of lung cancer. CLBH589CAU02T inherited forms, and prevalence in high risk groups. Brown M A phase 3, randomized, double-blind, placebo-controlled study of Gentilcore D The effects of acarbose on the blood pressure, heart rate and abiraterone acetate (CB7630) plus prednisone in patients with metastatic splanchnic blood flow responses to intraduodenal sucrose in healthy older castration-resistant prostate cancer who have failed docetaxel-based subjects. chemotherapy. COU-AA-301 Gentilcore D Effects of the oligosaccharide, alpha-cyclodextrin, on Carruthers S Randomised phase III trial comparing concurrent postprandial blood pressure in healthy older subjects – relationships to chemoradiation and adjuvant chemotherapy with pelvic radiation alone in gastric emptying, glycaemia and superior mesenteric blood flow. high risk and advanced stage endometrial carcinoma. PORTEC-3, CKTO Gill G A double blind randomized placebo controlled Phase III study to 2006-04, CME P06.031 assess the efficacy of recMAGE-A3 + AS15 ASCi as adjuvant therapy in Carruthers S A randomised phase III study of radiation doses and patients with MAGE-A3 positive resected stage III melanoma. fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of Gill G A multicentre randomised trial of sentinel lymph node biopsy versus the breast. TROG 07.01 axillary clearance in operable breast cancer. SNAC2 Casson R A 12 month, phase 3, single-centre, randomised trial to compare Greville H A randomised, double blind, placebo controlled, parallel group the safety and efficacy of a 1.25mg/0.5mL bevacizumab intravitreal injection study to investigate the safety and efficacy of two doses of tiotroium bromide to the macular grid laser therapy in the treatment of macular edema following (2.5ug and 5 ug) administered once daily via the Respimat device for 12 Branch Retinal Vein Occlusion (BRVO). weeks in patients with cystic fibrosis. Casson R Travoprost / Brinzolamide fixed combination vs TRAVATAN and Greville H A multicentre, open-label, single arm, proof of concept study to vs AZOPT. C-07-63 evaluate safety, tolerability and effect on sputum Pseudomonas Aeruginosa Casson R density on inhaled ciprofloxacin in adult patients with cystic fibrosis. Cipro Safety and efficacy study of Travoprost APS versus TRAVATAN®. C-08-10 in CF ARD-3100-0702

81 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL STUDIES of South Australia’s medical research

Greville H A Phase 3, international, multi-center, randomized, double-blind, Jenkins S Clinical implementation of a head mounted display for placebo-controlled, parallel-group, efficacy and safety study of Denufosol anaesthesia patient monitoring. Tetrasodium inhalation solution in patients with cystic fibrosis lung disease Keefe D A randomised double blind, parallel group study conducted under and FEV1 = 75% but 110% = predicted. in house blinding conditions to determine the efficacy and tolerability of Harley H A randomized, double-blind, placebo-controlled, Phase III trial of Aprepitant for the prevention of chemotherapy induced nausea and vomiting 2 regimens of telaprevir (with and without delayed start) combined with associated with moderately emetogenic chemotherapy. MK0869-130 EMEND pegylated interferon alfa-2a (Pegasys) and ribavirin (Copegus) in subjects Kimber T Open-label, 6-12 months safety and efficacy study of levodopa- with chronic genotype 1 hepatitis C infection. carbidopa intestinal gel in levodopa-responsive subjects with advanced Hecker J A phase 2 multicentre, randomized, double blind, placebo- Parkinson’s disease and severe motor-fluctuations. Protocol S187.3.004 controlled study of the safety, tolerability, and pharmacokinetics of multiple Kimber T A prospective, randomised, double-blind, double-dummy parallel doses of PF-04360365 in patients with mild to moderate Alzheimer’s disease. group multi-centre, event driven, non inferiority study comparing the efficacy A9951002 and safety of once daily oral Rivaroxaban (BAY59-7939) with adjusted dose Heddle B A single centre, randomised, controlled Phase 1/2 study of adults oral Warfarin for the prevention of stroke and non central nervous system with bee venom allergy to evaluate the safety and efficacy of a bee venom systemic embolism in subjects with non valvular atrial fibrillation. ROCKET desensitisation regime containing inulin adjuvant. Study P1-BEE001 Kneebone C TYSABRI Observational Program (TOP). Hetzel D A phase 2/3 multicenter, randomised, placebo-controlled, double- Lewis I A phase III, randomized, double-blind, placebo-controlled study to blind study to evaluate the safety and efficacy of Golimumab induction evaluate the efficacy and safety of prochymal (ex-vivo cultured adult human therapy, administered intravenously, in subjects with moderately to severely mesenchymal stem cells) infusion in combination with corticosteroids for the active ulcerative colitis. C0524T16 treatment of newly diagnosed acute GVHD. Osiris265 Hetzel D Efficacy and safety of oral budesonide-MMX (CB-01-02) 6 mg Lewis I A multicenter, double-blind, randomized, placebo-controlled, dose- and 9 mg extended release tablets in patients with mild or moderate active ranging trial evaluating the safety and efficacy of RI-001 in medically ulcerative colitis. A multicentre, randomised, double-blind, double-dummy, immunosuppressed Respiratory Syncytial Virus (RSV) infected patients at comparative study versus placebo with an additional reference arm risk of lower tract RSV illness. ADMA001 evaluating entocort® EC. CB-01-02/02 Lewis I An open label randomised controlled dose escalating phase II study Hetzel D A randomised, double-blind, parallel study of rabeprazole of AS1411 combined with cytarabine in the treatment of patients with primary extended-release 50mg versus esomeprazole 40mg for healing and refractory or relapsed acute myeloid leukaemia. AS1411-C-201 symptomatic relief of moderate to severe erosive gastroesophageal reflux Lewis I A phase 3, randomized, double blind, multicentre study of disease (GERD). E3810-G000-302 proteinase 3 PR1 peptide mixed with montanide ISA 51 VG adjuvant and Hetzel D 5 year registry study of HUMIRA (Adalimimab) in patients with administered with GM-CSF in elderly patients with AML in first complete moderately to severely active Crohn’s Disease. P06-134 remission or adults in second complete remission: A pivotal study. TVC Hetzel D A Phase 3 randomized, placebo-controlled, blinded, multicenter PR01-104 study of the induction and maintenance of clinical response and remission Ludbrook G A randomized, double-blind, placebo-controlled, phase 1/2 by MLN0002 in patients with moderate to severe ulcerative colitis. trial of Embrel® (Etanercept) administered by the transforaminal epidural Hetzel D A Phase 3, randomized, placebo-controlled, blinded, multicenter route for the treatment of lumbosacral radiculopathy. Protocol BDCISP- study of the induction and maintenance of clinical response and remission 2ENBREL by MLN0002 in patients with moderate to severe Crohn’s disease. Protocol Ludbrook G A double-blind, multi-centre, placebo-controlled trial of SABER No. C 13007 – Bupivacaine for post-operative pain control and opioid sparing/opioid Hetzel D A phase III, randomised, double-blind, dose response, stratified, related adverse event reduction following arthroscopic shoulder surgery. placebo-controlled study evaluating the safety and efficacy of SPD476 versus C803-017 placebo over 104 weeks in the prevention of recurrence of diverticulitis. Ludbrook G Pharmacokinetics of subcutaneous tramadol in healthy SPD476-313 volunteers. Holmes M A phase III, 26-week, multi-center randomized double-blind, Luscombe-Marsh N Acute effects of high-protein as compared to high-fat placebo-controlled, parallel-group study to assess the efficacy, safety and oral preloads on thermogenesis, appetite perceptions and energy intake and tolerability of indacaterol (150 & 300 µg o.d.) in patients with chronic the relationship with antropyloroduodenal motility, gastric emptying and gut obstructive pulmonary disease (COPD). Study S hormone release in overweight men. Holmes M A randomised, double-blind, double dummy, placebo- Mahar L A randomized, double-blind, placebo-controlled study of the safety controlled, parallel-group, multicenter dose ranging study to evaluate the and tolerability of E5555, and its effects on markers of intravascular efficacy and safety of GW685698X inhalation powder once a day and inflammation in subjects with coronary artery disease. E5555-G000-201 Fluticasone Propionate 500mcg inhalation powder twice daily compared with McLean A Medical conditions as a contributing factor in crash causation. placebo for 8 weeks in adolescent and adult subjects with persistent asthma symptomatic on moderate dose ICS therapy. FFA109684 Molaee P Assessment of left atrial function in patients with severe mitral stenosis. Holtmann G Complementary and alternative medicine grant application: A randomised placebo-controlled trial of a herbal preparation in functional Nguyen J An investigation of the therapeutic properties of human universal dyspepsia: cost effectiveness and mechanisms. energy treatment, during External Beam Radiotherapy (EBRT) for early stage prostate and breast cancer. HUE and QOL study Holtmann G Association of mucosal and peripheral immune activation with symptom patterns and co-morbidity in patients with functional Norman R Multi-center, double-blind, randomized study to Investigate the gastrointestinal disorders. impact of a sequentialoral contraceptive containing estradiol valerate and dienogest (SHT00658ID) compared to a monophasic contraceptive Hughes T A worldwide, observational registry collecting longitudinal data containing ethinylestradiol and levonogestrel (Microgynon) over & treatment on the management of Chronic Myelogenous Leukemia (CML) patients (The cycles on alleviating complaints of reduced libido in women with acquired WORLD CML Registry) in routine practice. female sexual dysfunction (FSD) associated with oral contraceptive use. Hustig H Randomised, double-blind, parallel-group, placebo-controlled and Norman R A multicenter, randomized, double-blind, active-controlled, active referenced study of Lu AA34893 to evaluate the efficacy and safety of parallel group, 2-arm study to investigate the effect of estradiol three doses Lu AA34893 and quetiapine versus placebo in the treatment of valerate/dienogest compared to Microgynon on hormonal withdrawal depression in patients with Bipolar I or II. associated symptoms in otherwise healthy women after 6 cycles of treatment.

82 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL STUDIES of South Australia’s medical research

Oehler M Profiling of the immunoproteome in early ovarian cancer. Rolan P The utility of saccadic eye movements and dynamic pupilometry to Patton N Compassionate use protocol for the use of AMD3100 to mobilise assess the interaction between circadian rhythm in alertness and sleep peripheral blood stem cells for collection and transplantation. AMD3100- deprivation with acute opioid administration in healthy volunteers. CUP001 Roodenburg O A prospective, randomised, double-blind, double-dummy, Peh CA A randomised, double-blind, placebo-controlled, factorial-design multicenter study to assess the safety and efficacy of doripenem compared trial to assess the effect of aspirin and fish oil (omega-3 fatty acids) in the with imipenem in the treatment of subjects with ventilator-associated prevention of early thrombosis in arterio-venous fistulae in patients with pneumonia. DORINOS3008 Stage IV or V chronic kidney disease requiring haemodialysis. FAVOURED Sanders P Patient notifier feature for reduction of anxiety: a multicenter ICD Study. study. PANORAMIC CR06002HV Penhall R A 24 week, multicenter, open-label evaluation of compliance and Sanders P Accuracy and clinical outcomes associated with CARTO XP+/- tolerability of the once daily 10cm2 Exelon Patch formulation in patients with v9 ultrasound for the guidance of AF ablation: a randomised controlled trial. probably Alzheimer’s. CENA713DAU01 Sanders P Catheter ablation versus standard conventional treatment in Penniment M Radiotherapy with humidification in head and neck cancer. patients with left ventricular dysfunction and atrial fibrillation. CASTLE-AF TROG 07.03 Sanders P First line radiofrequency ablation versus antiarrhythmic drugs Pohl A A phase 2 randomized, controlled, open-label (dose-blinded), multi- for atrial fibrillation treatment: A multi-center randomised trial. RAAFT center, dose-finding study of the safety and efficacy of I-0401 in the treatment Sanders P Delayed termination of atrial fibrillation following cardioversion. of patients with fractures of the tibial plateau requiring grafting. Selva Nayagam S A phase II trial evaluating the efficacy and safety of CS I-040101/02 epirubicin and cyclophosphamide (EC) followed by docetaxel with Proudman S Clinical phase 1/11A study of subcutaneous administration of gemcitabine (DG) (+trastuzumab if HER2 positive) as neoadjuvant ofatumumab in rheumatoid arthritis patients on stable dose of methotrexate. chemotherapy for women with large operable or locally advanced breast OFA110867 CM5108 cancer. Prowse R A phase 3, multicenter, randomised, double-blind, placebo- Selva Nayagam S A phase II, dose-escalation to rash trial of Erlotinib controlled, parallel group efficacy and safety trial of bapineuzumab (AAB- (Tarceva®) plus Gemcitabine in patients with metastatic pancreatic cancer. 001) in subjects with mild to moderate Alzheimer’s disease who are BO21128 apoliprotein Ee4 non-carriers. 3133K1-3000-WW Selva Nayagam S A randomised, open label, phase III study of taxane Prowse R A phase 3, multicenter, randomised, double-blind, placebo- based chemotherapy with lapatinib or trastuzumab as first line therapy for controlled, parallel group efficacy and safety trial of bapineuzumab (AAB- patients with HER2/neu positive metastatic breast cancer. EGF108919 001) in subjects with mild to moderate Alzheimer's disease who are Selva Nayagam S A randomized, double-blind, placebo-controlled, apoliprotein Ee4 carriers. 3133K1-3001-WW multicenter Phase II study to compare the efficacy and tolerability of Prowse R Effect of Á-secretase inhibition on the progression of Alzheimer ’s pazopanib administered in combination with exemestane versus exemestane disease: LY450139 versus placebo. IDENTITY H6L-MC-LFAN(b) plus placebo in postmenopausal subjects with advanced or metastatic Rayner C The effect of glucagon-like peptide-1 analogue, exanatide on hormone receptor positive breast cancer. VEG 108843 duodenal motility and flow events and small intestinal transit in healthy Shaw D A multi-center, randomized, double-blind, active-control, 96 week, humans and patients with type 2 diabetes mellitus. phase III trial of efficacy and safety of clevudine compared with adefovir at Rayner C Effects of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor, weeks 48 and 96 in nucleoside treatment-naïve patients with HBeAG positive on blood glucose and plasma incretin and insulin responses to small chronic hepatitis due to hepatitis B virus. CI-PSI-5268-06-306 intestinal glucose infusion, in healthy lean and obese subjects, and alone or Shaw D A multi-center, randomized, double-blind, active-control, 96 week, in combination with metformin in patient phase III trial of efficacy and safety of clevudine compared with adefovir at Rayner C Regulation of small intestinal sweet taste receptor expression by weeks 48 and 96 in nucleoside treatment-naïve patients with HBeAG negative luminal glucose exposure and blood glucose concentrations in healthy chronic hepatitis due to hepatitis B virus. CI-PSI-5268-06-305 humans and patients with type 2 diabetes mellitus. Shaw D A phase III randomized, double-blind trial of TMC278 25mg q.d. Rayner C Gastrointestinal determinants of vascular risk in healthy humans versus efavirenz 600mg q.d. In combination with a background regimen and patients with type 2 diabetes mellitus. containing 2 nucleoside/nucleotide reverse transcriptase inhibitors in anti- Reynolds P Improving clearance of dead cells to treat chronic bronchitis retroviral naive HIV-1 infected subjects. TMC2 and emphysema. Singhal N Phase 2, single-arm, open-label, multi-center trial of second-line Reynolds P The AMAZES study: Asthma and macrolides: the Azithromycin panitumumab monotherapy in patients with metastatic or recurrent squamous efficacy and safety study cell carcinoma of the head and neck. 20062088 PRISM Reynolds P Open label extension study in patients with idiopathic Singhal N A phase III randomised study of brivanib alaninate (bms- pulmonary fibrosis who completed protocol AC-052-321(BUILD 3). 582664) in combination with cetuximab (Erbitux) in patients previously AC-052-322 treated with combination chemotherapy for metastatic colorectal carcinoma. CO.20 Ritchie B Multicenter, randomized, pilot phase 1 study to evaluate the combination of an HCV polymerase inhibitor (RO5024048) and HCV Singhal N A randomised phase II trial of weekly docetaxel (Taxotere) protease inhibitor (RO5190591) in genotype 1 chronic hepatitis C patients. chemoradiotherapy +/- cetuximab (Erbitux) in the treatment of localised Protocol PP22205/A (CM5608). resectable cancer of the oesophagus. DECO AG0307OS Rolan P A comparison of opioid tolerance and opioid-related Smith B Smoking termination opportunity for inpatients. STOP hyperalagesion when produced by remifentanil with “sawtooth” plasma Smith W An open label study of Ig NextGen 16% administered by profiles compared to standard “flat” profiles in healthy volunteers. subcutaneous infusion in patients with primary Immunodeficiency (PID). Rolan P A study of the effect of circadian rhythm on the sedative effects of CSLCT-SCIG-07-42 buprenoorphine in alternate-day dosed buprenorphine-maintained patients. Solomon L Correlation of abductor morphology, innervation and power Rolan P A comparison of cold pain tolerance as a measure of opioid-related after hip replacement surgery. hyperalgesia in patients receiving chronic codeine therapy compared to Solomon L Abductor muscles function after hip arthroplasty. A clinical healthy volunteers. testing, EMG and MRI study.

83 Annual Report 2008 Hanson Institute Proudly bringing together the best CLINICAL STUDIES of South Australia’s medical research

Solomon L Intramedullary nailing versus external fixation in closed tibial Wittert G A multicentre, randomised, double blind, placebo controlled shaft fractures. A randomised clinical trial. study to assess the efficacy, safety and tolerability of taspoglutide Solomon L Tibial plateau fracture outcome review. (RO5073031) compared to placebo in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. BC20750RG Solomon L The trochanteric micromovement after primary total hip arthroplasty: a pilot human study using radiostereometric analysis. Wittert G A multicenter, randomised, double blind, double dummy, placebo and active controlled study to assess the efficacy, safety and tolerability of Soulsby N Inhaled tobramycin as a treatment option for hospitalised taspoglutide (R05073031) compared to sitagliptin and placebo in patients patients with cystic fibrosis. with type 2 diabetes mellitus inadequately controlled with metformin. Sutherland P A comparison of psychosocial outcomes following Tadalafil BC21713 once a day or PDE5 inhibitor as needed in men with erectile dysfunction. Wittert G A phase III open label titration trial to evaluate the effectiveness H6D-CR-S024 and safety of different doses of a dermal application of Testosterone MD- Sutherland P Pivotal phase III trial to investigate the efficacy and safety of Lotion® (cutaneous solution) in hypogonadal men. MTE08 an orodispersible tablet vardenafil versus placebo in the treatment of men Worthley M Study of coronary Atheroma by InTravascular Ultrasound: with erectile dysfunction (ED) a fixed-dose, double-blind, randomized multi- Effect of Rosuvastatin Versus AtorvastatiN (SATURN). A 104-week, center trial. POTENT II randomized, double-blind, parallel group, multi-center Phase IIIb study Sweeney C A phase 1b/2 study to assess the safety and efficacy of AMG comparing the effects of treatment with rosuvastatin 40mg or atorvastatin 102 in combination with mitoxantrone and prednisone in subjects with 80mg on atherosclerotic disease burden as measured by intravascular previously treated castrate resistant prostate cancer. 20070611 ultrasound in patients with coronary artery disease. Sweeney C A phase 3b randomised, open-label study of bevacizumab Worthley S Bare metal bifurcation stent clinical trial in humans. (Avastin) and temsirolimus vs. bevacizumab (Avastin) and Interferon-alpha The Medtronic BRANCH clinical trial IP#088. (Roferon) as first line treatment in subjects with advanced renal cell Worthley S A multi-center study evaluating the safety of the Osprey medical carcinoma. 3066K1-3311-WW contrast removal system. TP-6067-03 Sweeney C Pilot study evaluating genetic variants leading to non-small cell Worthley S A randomized, multi-centre, single-blind comparison of the lung cancer in females with minimal smoking history. conor cobalt chromium reservoir based stent with sirolimus elution versus Sweeney C A phase II multi-centre trial of a seven day aprepitant schedule the TAXUS liberte paclitaxel-eluting coronary stent system in de novo native for the prevention of chemotherapy induced nausea and vomiting in patients coronary artery lesions. The RES-ELUTION Study. receiving five day cisplatin-based chemotherapy for germ cell tumours. Worthley S A multicenter, randomised, double-blind, placebo-controlled Short name: Aprepitant for Germ Cell Chemotherapy or Aprepitant Trial. study to evaluate the safety and efficacy of SCH 530348 in addition to Sweeney C A phase I study to determine the safety and pharmacokinetics standard of care in subjects with a history of atherosclerotic disease: of ascending single IV doses of ALD518 80mg, 160mg, 320mg and 640 mg Thrombin receptor antagonist in secondary prevention of Atherothrombotic administered as a single dose to patients with advanced cancer and a phase Ischemic Events. TRA 2P-TIMI 50 II study of the safety and efficacy of ALDS518 IV. Yeoh E Phase II prospective non-randomized trial of the use of conformal Sweeney C Randomised study of larotaxel and cisplatin (LC) versus high dose rate brachytherapy alone for the treatment of favorable stage gemcitabine and cisplatin (GC) in the first line treatment of locally advanced adenocarcinoma of the prostate. P-BIG / metastatic urothelial tract or bladder cancer. EFC6668 Young G Effects of dietary administration of n-3 polyunsaturated fatty acids Sweeney C NPI-0052 and Vorinostat in Patients with Non-Small Cell Lung on cardiac electrophysiology in humans. Cancer, Pancreatic Cancer or Melanoma. Protocol No.NPI 0052-103 Sweeney C Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer. PETACC-6 Sweeney C A multinational, randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of AVE5026 in the prevention of venous thromboembolism (VTE) in cancer patients at high risk for VTE and who are undergoing chemotherapy. SAVE-ONCO, EFC6521. Thompson S Prognostic impact of micrometastases in oesophageal cancer – applying the sentinel lymph node concept. Tilley W Androgen Receptor activity in normal and abnormal human ovarian function. To B An Australasian, phase II, multicentre, randomised, dose intensification study investigating oral fludarabine, oral cyclophosphamide and i.v. rituximab (poFCivR) tolerance in previously untreated elderly (≥ 65 years old) patients with chronic lymphocytic (CLL). ALLG CLL5 Torpy D A multicenter, randomized, blinded study to assess the safety and efficacy of pasireotide LAR vs. octreotide LAR in patients with active acromegaly IM depot injection. CSOM230C2305 Torpy D The effect of continuous subcutaneous hydrocortisone infusion (CSHI) pump therapy in Addison’s disease on subjective health status: A double-blind, randomised, placebo-controlled clinical trial. Torpy D Survey of pregnant outcomes in women with Addison’s disease. Vink R Diagnostic and prognostic evaluation of diffusion tensor imaging and cognitive function after traumatic brain injury. Outcome after Head Injury. White J Effects of food on the oral bioavailability of R-methadone in healthy subjects.

84 Annual Report 2008 Hanson Institute Proudly bringing together the best INVITED PRESENTATIONS of South Australia’s medical research

Major national and international presentations Buchanan G Atkins G Speaker • ‘AR mechanisms’, Fourth Pacific Rim Breast and Prostate Cancer Meeting, Speaker Whistler, British Columbia, Canada • ‘Human osteoblast differentiation – modelling the osteocyte’, 5th Clare • ChIP-chip linked activity profiling of the androgen receptor: collaborators Valley Bone Meeting, Clare, South Australia and the contextual hierarchy of the transcriptional response’, West Beard M Australian Institute of Medical Research Seminar Program, Perth, Western Speaker Australia • ‘Hepatitis C virus and innate immunity’, 2nd International Symposium on Butcher C Infection and Immunity, Beijing, China and Fudan University Shanghai, Organising Committee Member Shanghai, China • New Directions in Leukaemia Research Conference (NDLR 2008) Chair Butler L • Innate Immunity Session, 15th International Symposium on HCV and Related Viruses, San Antonio, Texas, USA Speaker • ‘Androgen receptor signalling in prostate cancer: new insights into Convenor targeted therapies’, Endo 08 (Endocrine Society USA Annual Meeting), • Australian Centre for Hepatitis Virology (ACHV), Annual Scientific San Francisco, California, USA Meeting, Barossa Valley, South Australia • ‘A novel combinatorial approach for treatment of prostate cancer’, Bignold L Australian Health and Medical Research Congress, Brisbane, Queensland Speaker Session Chair • ‘The “aneuploidy-modified mutator-phenotype” theory of malignant • Symposium on Origin and Progression of Prostate Cancer, Endo 08 tumours’, 2nd Conference on Chromosomes and Cancer, Oakland, (Endocrine Society USA Annual Meeting), San Francisco, California, USA California, USA Casson R • ‘DNA-protein clamp dysfunction as a mechanism of chromosomal aberrations’ and ‘David Paul Hansemann, chromosomes and cancer’, Speaker 8th International Conference of Anticancer Research, Kos, Greece • ‘The basic science/clinical interface in ophthalmology: more than meets the eye’, Council Lecture, Royal Australian & New Zealand College of Blackshaw LA Ophthalmologists Scientific Congress, Melbourne, Victoria Speaker Cleland L • ‘Nociceptors – new biology’ Symposium, Official Satellite meeting, 12th World Congress on Pain, Edinburgh, Scotland Speaker • ‘Sensory function and dysfunction of the esophagus’, San Diego, USA • ‘Medicinal use of fish oil’, Medical Grand Rounds, Princess Alexandra • ‘Oesophageal structure and function in health and disease’, International Hospital, Brisbane, Queensland Meeting on the Oesophagus, Adelaide, South Australia • ‘Fish oil as an NSAID substitute’, RACP Trainees Preceptor Course, • ‘Professional skills needed to build a successful career in medical Australian Rheumatology Association National Scientific Meeting, research’, ASMR Professional Development Program, Adelaide, South Adelaide, South Australia Australia • ‘From medicine’s age of reason to bone and joint decadence and beyond’, • ‘Pathways to pain’, Plenary Lecture, 2nd Joint International Meeting on SC Milazzo Oration, Australian Rheumatology Association National Neurogastroenterology and Motility, Lucerne, Switzerland Scientific Meeting, Adelaide, South Australia • ‘Omega-3s for the body?’ Inflammation, including arthritis’, Omega-3 Bonder C Centre Consensus Meeting, CSIRO, Sydney, New South Wales Speaker Coyle P • ‘Sphingosine kinase: a regulator of endothelial progenitor cell differentiation’, 12th Australasian Autoimmunity Workshop, Sydney, New Speaker South Wales • ‘Birth defects and cognitive impairments caused by acute alcohol exposure ‘binge’ in early pregnancy: Is zinc deficiency involved?’, National Organising Committee Member Conference on Alcohol in Pregnancy: Is Any Too Much?, Monash • 13th Australasian Autoimmunity Workshop, Adelaide, South Australia University, Victoria • 4th Barossa Signalling Meeting, Adelaide, South Australia Brierley S D’Andrea R Speaker Speaker • ‘Novel and specific roles for the ion channel TRPA1 in visceral sensory • ‘Translocation-specific gene expression changes in AML: potential leads transduction’, 6th Annual Functional Brain-Gut Research Group’s for therapy’, New Directions in Leukaemia Research Conference (NDLR Functional GI Disorders Young Investigators Forum, La Jolla, California, 2008), Queensland USA • ‘Using gene expression profiling to identify potential AML therapies’, Brown A HSANZ/TIGSA, Conjoint Scientific Meeting, Clare, South Australia Organising Committee Member Co-Chair • New Directions in Leukaemia Research Conference (NDLR 2008) • Organising and Scientific Committees, New Directions in Leukaemia Brown M Research Conference (NDLR 2008) Speaker Elshaug AC • ‘Interactive clinical case session’, Case Presentation of Metastatic Non Keynote Speaker small Cell Lung Cancer, Lilly Oncology Asia Pacific Thoracic Cancer • ‘Disinvestment from existing ineffective health care practices’, Introducing Regional Medical Conference, Hong Kong Innovation in Healthcare Systems, EuroScan and Osteba Conference, Bilbao, Spain

85 Annual Report 2008 Hanson Institute Proudly bringing together the best INVITED PRESENTATIONS of South Australia’s medical research

Evdokiou A Speaker Speaker • ‘Aspects of a successful career in science’, Career Development Lecture, • ‘From lab bench to bedside and back’, ARCS 17th Annual Scientific Department of Human Biology, Technical University of Munich, Germany Congress, Sydney, New South Wales • ‘How I built a career in physiological science’, Career Development • ‘Bone metastasis models and therapeutic interventions’, Australian Health Workshop, Young Investigator Meeting, 2nd Joint International Meeting & Medical Research Congress, Brisbane, Queensland for Neurogastroenterology and Motility, Lucerne, Switzerland • ‘Bone metastasis and cancer therapy through trials of new generation • ‘Recent topics nutrition – Dietary influence on GI functions and functional drugs such as ApoZL/TRAIL’, National Breast Cancer Foundation, GI diseases’, Department of Human Biology, Technische Universität, Canberra, Hobart, Darwin and Perth, Australia München, Germany • ‘Satiety signals from the gut’, Annual Meeting of the Society for the Study Fazzalari N of Ingestive Behavior, Paris, France Convenor and Speaker • ‘Relationships between gastrointestinal function and acute energy intake’, • ‘Bone and gene studies in osteoporosis: why are they important?’, and Annual Scientific Meeting of the Nutrition Society of Australia, Adelaide, ‘Keeping bones well’, 5th Clare Valley Bone Meeting, Clare, South South Australia Australia Gibson R Speaker Speaker • ‘Bone and genes: Exploring their relationship’, Rheumatology Department, • ‘Leading lights of South Australia’, ASMR Annual Scientific Meeting, University Orléans, France Adelaide, South Australia • ‘Structure overload and structural anisotropy in human vertebral trabecular bone’, International Congress on Theoretical and Applied Goldney R Mechanics, Adelaide, South Australia Speaker • ‘Structural and molecular characteristics of trabecular bone in primary hip • ‘Suicide: Do we know more than 19th century alienists? Was there suicide osteoarthritis’, Australian Rheumatology Association, 50th National research before Durkheim?’, Valedictory Scientific Meeting for Professor Meeting, Adelaide, South Australia G Burrows, Melbourne, Victoria • ‘Fracture and failure of bone – how and why?’ (Bone Pathways!), • ‘Antidepressants and suicide: What the media don’t report’, Asia-Pacific Australian Bone Academy, Melbourne, Victoria Coroners Society Conference, Adelaide, South Australia Session Chair • ‘Depression, suicide and antidepressants: With a focus on younger • Session 4, Bone Strength, Australian and New Zealand Bone and Mineral persons’, Specialist Symposium on Mental Health – Dimensions of Society, Melbourne, Victoria Depression, Melbourne, Victoria Member Goodall GJ • Board Member, International Society for Fracture Repair Speaker • Council Member, Australian and New Zealand Bone and Mineral Society • ‘MicroRNAs involved in epithelial-mesenchymal transition; Centenary • Council Member, Australian and New Zealand Orthopaedic Research Colloquium IV ‘Opportunities in RNA Based Therapeutics’, Sydney, New Society South Wales Findlay D • ‘Regulation of EMT by the miR-200 family of microRNAs and its implications for cancer’, HMRI Cancer Conference 2008, Newcastle Speaker • ‘MicroRNAs and breast cancer’, 4th International PacRim Breast and • ‘The osteocyte’, Australian and New Zealand Bone and Mineral Society Prostate Cancer Conference, Whistler, BC, Canada Postgraduate Meeting, Melbourne, Victoria • ‘Regulation of EMT by the miR-200 family of microRNA’, 2008 • ‘Osteocytes: the cells within’, 14th Annual Scientific Meeting, Australian Queenstown Molecular Biology Meeting, New Zealand and New Zealand Bone and Mineral Society, Melbourne, Victoria • ‘Role of the miR-200 family in mediating EMT in response to TGF-beta’, • ‘Microarray gene expression profiling of human osteoarthritic bone Cytokines 2008, Montreal, Canada suggests altered bone remodelling, wnt and TGF beta/BMP signalling’, • ‘Regulation of EMT by the miR-200 family of microRNAs’, Baker Heart (Findlay, Hopwood, Tyskin, Fazzalari), Osteoarthritis Research Society Research Institute, Melbourne International World Congress, Rome, Italy • ‘Regulation of EMT by the miR-200 family of microRNAs and its • ‘The role of TWEAK in bone’ and ‘Osteocytes: the basis of healthy bone’, implications for cancer’, Ludwig Institute for Cancer Research-Austin, (Findlay, Atkins), Third International Congress of Chinese Orthopaedic Melbourne and Peter MacCallum Cancer Centre, Melbourne Association, Suzhou, China • ‘Regulation of EMT by the miR-200 family of microRNAs’, John Curtin • ‘TNF family proteins in bone’, Rheumatology Section, Molecular Medicine School for Medical Research, Canberra, and The Murdoch Childrens Centre, University of Edinburgh, Western General Hospital, Edinburgh, Research Institute, University of Melbourne Scotland • ‘TNF family proteins in bone’, Department of Orthopaedic Surgery, Mt Greenwood J Sinai Hospital, New York; Department of Rheumatology and Orthopaedics, Speaker Hospital for Special Surgery, New York; Kansas City Bone and Tooth • ‘Burn care innovations’, Governor’s Leadership Foundation, Adelaide, Seminar Series, Kansas City, Missouri, USA; and Diamantina Institute, South Australia Brisbane, Queensland • ‘Burns and the hand’, Combined Conference of Australian Faculty of Conference Organiser Occupational and Environmental Medicine and Australian Faculty of • Member, Organising Committee, 5th Clare Valley Bone Meeting, Clare, Rehabilitation Medicine, Adelaide, South Australia South Australia • ‘The use of CEA and bioengineered products in burn wounds’, Masterclass, Conjoint Annual Scientific Congress, Royal Australasian Feinle-Bisset C College of Surgeons and College of Surgeons of Hong Kong, Hong Kong Plenary Session Chair • ‘Planning for mass burn casualties in South Australia’; Design and • ‘Food intake, obesity and brain-gut interactions’, Annual Meeting of the synthesis of biodegradable polymers to create dermal regeneration American Gastroenterological Association, San Diego, California, USA scaffolds’; ‘Biodegradable polymers – (i) in vitro evaluation as dermal • ‘Gastrointestinal dysfunction: moving forward’, Joint International Meeting matrices’; ‘Biodegradable polymers (ii) in vivo evaluation as dermal of Neurogastroenterology and Motility, Lucerne, Switzerland matrices’, Conjoint Annual Scientific Congress, Royal Australasian • ‘Clinical research’, Annual Meeting of the Australian Society for Medical College of Surgeons and College of Surgeons of Hong Kong, Hong Kong Research, Adelaide, South Australia

86 Annual Report 2008 Hanson Institute Proudly bringing together the best INVITED PRESENTATIONS of South Australia’s medical research

• ‘Design, synthesis and preliminary evaluation of NovoSorb™ Programme Committee biodegradable polymers to create an ideal dermal regeneration matrix’, • International Scientific Programme Committee for the VIIIth Annual ANZAC Research Institute, 7th Annual Conference, Concord Hospital, meeting, Health Technology Assessment International, Brazil, 2008-2011 Sydney, New South Wales Hercus T Gregory PA Speaker Speaker • ‘The structure of the GM-CSF receptor complex reveals a new mode of • ‘A double-negative feedback loop between the microRNA-200 family and cytokine receptor activation, Keystone Symposium on Structural Biology the E-cadherin repressors ZEB1 and SIP1 regulates epithelial- and Activation Mechanisms of Membrane Receptors, St John’s College, mesenchymal transition’, COMBIO 2008, Canberra University of Cambridge, England • ‘The microRNA-200 family and miR-205 regulate epithelial-mesenchymal Hodge S transition by targeting the E-cadherin repressors, ZEB1 and SIP1’, Cold Speaker Spring Harbor Laboratory meeting on Epithelial Mesenchymal Transition, • ‘COPD’, Australian Parliamentary Offices, Canberra Cold Spring Harbor, New York, USA • ‘Efferocytosis in COPD’, National Annual Asthma Meeting, Newcastle, Gustafsson J New South Wales Student Presentation Conference Chairperson • ‘Imaging mass spectrometry on murine nervous system tissues, 13th • American Thoracic Society Annual Scientific Meeting in 2009, San Diego, Proteomics Symposium, Lorne, Victoria USA Speaker • Asian Pacific Society of Respirology Annual Scientific Meeting: Allergy • ‘Imaging mass spectrometry (IMS) application to murine tissues’, 4th and Immunology Oral Session PRICPS-AOHUPO Conference, Cairns, Queensland • Asian Pacific Society of Respirology Annual Scientific Meeting: COPD Guthridge M Poster Session • TSANZ Annual Scientific Conference: Immunology and Cell Biology Speaker Poster Session • ‘A new cytokine receptor survival switch: What goes wrong in leukemia’, New Directions in Leukaemia Research Conference, Sunshine Coast, Hoffman P Queensland Speaker Session Chair • ‘Imaging mass spectrometry (IMS) of murine tissues using a piezoelectric • ‘Hot Topics’, New Directions in Leukaemia Research Conference, printer’, 4th PRICPS-AOHUPO Conference, Cairns, Queensland Sunshine Coast, Queensland Howie D Harvey N Speaker Speaker • ‘Lessons in periacetabular osteotomy’ and ‘THA or resurfacing in the • ‘Defining the role of macrophages in embryonic lymphangiogenesis’, The young patient’, Bernest Hip Symposium, Berne, Switzerland Hunter Cell and Developmental Biology Meeting, Hunter Valley, New • ‘Techniques in femoral impaction bone grafting including mechanical South Wales vibration’ and ‘Reporting survival of total hip replacement – the cemented polished double taper stem in young patients’, Arthroplasty Society of Hickey T Australia Annual Scientific Meeting, Canberra, Australia Speaker Hughes T • ‘Androgen receptor activity in the pathology of polycystic ovary syndrome’, Beijing International Congress of Reproductive Medicine, Speaker Beijing, China • ‘Optimizing therapy in patients with sub-optimal response’; ‘Risk based decision making in upfront therapy – is early response important’, Session Chair Advisory Board Meeting on CML GOLS, Prague, Czech Republic • ‘Breast density, HRT and breast cancer risk’, Four Pacific Rim Breast and • ‘Advances in chronic myelogenous leukaemia: an international Prostate Cancer Meeting, Whistler, British Columbia, Canada perspective’, Canadian Blood and Marrow Transplant Group, Montreal, • ‘Viva la difference: mammalian reproductive strategies’, Society for Canada Reproductive Biology Annual Meeting, Melbourne, Victoria • ‘TKIs in CML: same target, new power – Imatinib dose optimization’, EHA • ‘Androgens in women’, Endocrine Society of Australia Annual Scientific Congress, Copenhagen, Denmark Meeting, Melbourne, Victoria • ‘Molecular diagnostics in CML’; ‘Tyrosine kinase inhibitors and Organising Committee resistance’, South African Society of Haematology, Cape Town, South • Member, International Organising Committee, Fourth PacRim Breast and Africa Prostate Cancer Meeting, Vancouver, British Columbia, Canada • ‘Second generation TKI’, NZ HSANZ Haematology Update Meeting, • Member, Program Organising Committee, Society for Reproductive Queenstown, New Zealand Biology Annual Meeting, Melbourne, Victoria • ‘Predictive assays for de-novo CML patients receiving TKI therapy’, ESH Hiller JE CML Meeting, Boston, USA Speaker • ‘Dose optimization overcoming suboptimal response’; ‘Molecular • ‘Widgets, gadgets and other health technologies: using evidence, monitoring: is it feasible in clinical practice?’; ‘Update on emerging priorities and values to guide choices’, Research Tuesday Professorial treatment options for CML therapy’, GOLS Meeting, Buenos Aires, Brazil Seminar, University of Adelaide, South Australia • ‘How to measure minimal residual disease – FISH & PCR’, Leukaemia 2008, Houston, USA Session Chair • ‘The real deal with CML’, ASH Veritas Institute for Medical Education, 50th • ‘International perspectives on disinvestment from ineffective health care American Society of Haematology, San Francisco, USA practices’, 5th Annual Meeting, Health Technology Assessment • ‘Overcoming imatinib resistance in CML with second generation ABL International, Montreal, Canada kinase inhibitors’, NDLR, Sunshine Coast, Queensland Chair and Discussant • ‘Molecular diagnosis and monitoring of CML’, ISLH, Sydney, New • ‘A fresh perspective on health services research in South Australia’, Health South Wales Services Research Association of Australia and New Zealand, Adelaide, South Australia

87 Annual Report 2008 Hanson Institute Proudly bringing together the best INVITED PRESENTATIONS of South Australia’s medical research

James M Lopez A Keynote Speaker Speaker • ‘Rheumatoid arthritis and fish oil’, International Society of Fatty Acids and • ‘Biology of 14-3-3 proteins’, Gordon Research Conference, Ventura, Lipids meeting, Kansas City, USA California, USA Jilbert A • ‘A new mechanism of cytokine receptor activation’, New Directions in Leukaemia Research, Sunshine Coast, Queensland Speaker and Chair • ‘Pathogenesis’, International Meeting on the Molecular Biology of Morris H Hepatitis B Viruses, La Jolla, California, USA Speaker Speaker • ‘International Standardisation of Immunoassays’, Endocrine Society of • ‘Hepatitis B infections – update and overview’, Australian Society for Australia Annual Scientific Meeting Melbourne, Victoria Microbiology, Clinical Virology Seminar, Adelaide, South Australia • ‘Vitamin D deficiency and depletion: How much do we need for optimal • ‘Reactivation of Hepatitis B virus: the silent partner’, Adelaide health?’ and ‘Nomenclature, properties and units: The IFCC Philosophy’, Haematology Group, Adelaide, South Australia Australasian Association of Clinical Biochemists Annual Scientific Conference, Adelaide, South Australia Committee Member • ‘Traceability and standardisation of immunoassays’ and ‘Laboratory quality • Australian Centre for HIV and Hepatitis Virology Research, Scientific regulations and accreditation standards in Australia’, 1st International Meeting, Barossa Valley, South Australia Symposium on Quality and Standardisation in Laboratory Medicine, Keefe D Istanbul, Turkey Speaker Parkinson I • ‘Mucositis: the mouth ulcer and beyond’, Palliative Care Grand Rounds, Speaker University of Wisconsin, USA • ‘Prediction of bone strength: contribution of individual trabecular • ‘The changing face of medical oncology’, PRIME, SA GP Education elements’, 5th Clare Valley Bone Meeting, Clare, South Australia Weekend, South Australia • ‘Probiotics and diarrhoea’, Clinical Oncological Society of Australia, Pitson S Sydney, New South Wales Speaker Khew-Goodall Y • ‘Oncogenic signalling of sphingosine kinase 1 is controlled by the calcium-myristoyl switch protein CIB1’, Queenstown Signal Transduction Speaker meeting, Queenstown, New Zealand • ‘The PTP-Pez is a novel regulator of TGF-beta secretion: implications for health and cancer’, Lorne Cancer Conference, Victoria Ross I • ‘The PTP-Pez is a novel regulator of TGF-beta secretion: implications for Speaker health and cancer’, FASEB Summer Research Conference: Protein • ‘Salmonella molecular typing’, The Ozfoodnet and SA Health National Phosphatases, Colorado, USA Face-to-Face Meeting, Adelaide, South Australia • ‘The role of PTP-Pez and miR-200 microRNAs in TGF-beta-induced Scott H morphogenesis’, Combio 2008, Canberra, ACT Speaker Kumar S • ‘Using familial predispositions to haematological malignancies to follow Invited Chair disease progression’, New Directions in Leukaemia Research, • ‘Cell growth and differentiation’, Hunter Cell Biology Meeting, Pokolbin, Maroochydore, Queensland New South Wales • Familial predispositions to haematological malignancies’, Familial Cancer, Speaker Research and Practice 2008, Couran Cove, Queensland • ‘Regulation of the metal iron transporter DMT1 by ubiquitination’, Hunter • ‘Immunology meets genetics’, 4th Adelaide Immunology Retreat of the Cell Biology Meeting, Pokolbin, New South Wales Australian Society of Immunology, Normanville • ‘Ubiquitin and cellular regulation’, The FASEB Summer Research Smith L Conference, Saxtons River, Vermont, USA Speaker • ‘Cell Death’, (Late Breaking Hot Topics), Gordon Research Conference, • ‘Relationships between mineralisation and micromechanical properties Lucca (Barga), Italy within the individual remodelling packets of human femoral trabecular • ‘Regulation of receptors, transporters and ion channels by the Nedd4 bone spicules’, 5th Clare Valley Bone Meeting, Clare, South Australia family of ubiquitin ligases’, Australian Physiological Society Meeting, Stringer A Melbourne, Victoria Speaker Kumarasinghe D • ‘New thoughts on the pathobiology of mucositis’, Department of Speaker Pediatrics, UMCG, Groningen, Netherlands • ‘An examination of osteoblast gene expression in osteoarthritis’, 5th Clare • ‘Chemotherapy-induced modification to gastrointestinal microflora: Valley Bone Meeting, Clare, South Australia Evidence and implications of change’, Department of Microbiology, Logan R UMCG, Groningen, Netherlands Speaker Thompson PD • ‘Destructive lesions in the anterior maxilla’, Pathology Update, Royal Speaker College of Pathologists of Australasia, Sydney, New South Wales • ‘Movement disorder look-alikes: The great pretenders’, Video Session at • ‘The changing face of febrile neutropenia – from monotherapy to moulds 12th International Congress of Parkinson’s Disease and Movement to mucositis’, Mucosal Barrier Injury, Life Time Achievement Symposium, Disorders, Chicago, USA Middleburg, The Netherlands • ‘Unusual movement disorders – What is your diagnosis?’, Asian Scientific • ‘Serum levels of NF-kappaB and pro-inflammatory cytokines following Symposium on Parkinson’s Disease and Restless Legs Syndrome, Tokyo, chemotherapy’, Multinational Association for Supportive Care in Cancer, Japan International Symposium, Houston, Texas, USA

88 Annual Report 2008 Hanson Institute Proudly bringing together the best INVITED PRESENTATIONS of South Australia’s medical research

Tilley W Speaker • ‘Androgen receptor signalling in prostate cancer’, The American Association for Cancer Research Annual Scientific Meeting, San Diego, California, USA • ‘The role of androgen receptor in prostate cancer’, Sydney Cancer Conference, University of Sydney, New South Wales • ‘Ron Ross Award Oration’, Fourth Pacific Rim Breast and Prostate Cancer Meeting, Whistler, British Columbia, Canada • ‘Contribution of aberrant androgen receptor signalling to prostate tumorigenesis’, The Hunter Medical Research Institute Conference on Translational Cancer Research, Newcastle, New South Wales Co-Chair • International Advisory Group, Fourth PacRim Breast and Prostate Cancer Meeting, Vancouver, British Columbia, Canada Organising Committee • Member, International Organising Committee, Fourth PacRim Breast and Prostate Cancer Meeting, Vancouver, British Columbia, Canada Vink R Speaker • ‘Effects of magnesium on cognitive outcome following brain injury’, Gordon Conference on Magnesium in Biological Processes and Medicine, Ventura, California, USA • ‘Head trauma and secondary impact – Fact or fiction’, Asia-Pacific Coroner’s Society Conference, Adelaide, South Australia Wittert G Speaker • ‘Epidemiology of ageing males in Australia, 6th World Congress of the Ageing Male, Tampa, Florida, USA • ‘Obesity in the older male’, 6th World Congress of the Ageing Male, Tampa, Florida, USA • ‘Obesity and the metabolic syndrome, 15th International Congress on Dietetics Yokohama, Japan • ‘Metabolic syndrome and sexual dysfunction in men: implications for the cardiovascular system’ and ‘Type II diabetes mellitus: emerging treatment strategies and concepts’, Hypertension, Diabetes and Lipid Symposium, Shanghai, China • ‘How to implement a lifestyle management program’, GSK Gold Program for GPs and Specialists, Sydney, New South Wales • ‘Obesity and heart disease’, Cardiac Society of Australia and New Zealand, Adelaide, South Australia • ‘Obesity and sexual function in men’, Australian Health and Medical Research Conference, Brisbane, Queensland Zannettino A Speaker • ‘Mechanisms of bone loss in myeloma’, Myeloma Patient and Family Seminar, Myeloma Foundation of Australia, Adelaide, South Australia • ‘Elevated serum levels of CXCL12 is associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients’, Fifth Clare Valley Bone Meeting, Clare Valley, South Australia • ‘The use of prospectively isolated mesenchymal precursor cells (MPC) to repair bone defects’, Bio Innovation SA Networking Forum, Bio Innovation Osteo Networking Evening, Adelaide, South Australia • ‘Multiple myeloma’, Ansett “Down to Earth” Club Annual General Meeting, Adelaide, South Australia • ‘Efficacy of mesenchymal stromal cells (MSC) for the repair of skeletal tissues’, NCRIS 5.5 CGMP, Seminar Workshop “Nano-Engineering for Cells”, Adelaide, South Australia

89 Annual Report 2008 Hanson Institute Proudly bringing together the best AWARDS, APPOINTMENTS AND ACCOLADES of South Australia’s medical research

Ahern J Centenera M • Lung Research Laboratory, awarded Best Overall Poster at the Thoracic • Breast & Prostate Cancer Research Laboratories, awarded her PhD Society of Australia and NZ Annual Scientific Meeting ‘Characterisation of a Dominant Negative Androgen Receptor in Prostate Andrews J Cancer Cells’, University of Adelaide • Nerve-Gut Research Laboratory, appointed Associate Professor, University Cleland L of Adelaide • Arthritis & Rheumatology Research Laboratory, received the Unsung Hero Badiei A of South Australian Science Award 2008 • Bone and Joint Research Laboratory, awarded PhD with commendation, Colella A University of Adelaide ‘Trabecular bone structural anisotropy’ • Adelaide Proteomics Centre, awarded his PhD ‘The Genetic and Beard MR Biochemical Analysis of Drosophila Wwox Protein Function’ • Hepatitis C Virus Research Laboratory, received an Australian Academy of Condina M Science USA Travel Award • Adelaide Proteomics Centre, awarded 3rd poster prize, Lorne Proteomics Betterman K Symposium • Appointed SA representative of the Students of the Australasian • Lymphatic Development Laboratory, received a Best Poster Presenter Proteomics Society (SoAPS) Prize, University of Adelaide Faculty of Health Sciences Postgraduate Research Expo Cooper L Blackshaw LA • Mesenchymal Stem Cell Group & Regenerative Medicine Program, Bone & Cancer Laboratories, received a Dawes Scholarship from the RAH/SA • Nerve-Gut Research Laboratory, President of Australasian Pathology Research Committee Neurogastroenterology and Motility Association 2008 Coyle P Bong LF • Drugs and Metals Research Laboratory, appointed Affiliate Associate • Myeloma & Mesenchymal Research Group, awarded First Class Honours, Professor, Department of Medicine, University of Adelaide University of South Australia ‘The Effects of BEZ235, a Dual Pan Class I PI3 Kinase and mTOR Inhibitor, on Osteoblast Differentiation and Diener K Function’ • Arthritis & Rheumatology Research Laboratory, awarded her PhD Bowen J ‘Approaches Toward Inducing Active Prostate-Specific Immunotherapy, University of South Australia • Mucositis Research Group, Cancer Council South Australia recipient of Travel Grant to attend Multinational Association of Supportive Care in Dunn K Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual • Psychiatry, awarded her PhD ‘Fast-Food Consumption: Application and Scientific Meeting Extension of the Theory of Planned Behaviour to Incorporate Effective • MASCC Young Investigator Award Responses and Implicit Associations’, Psychology/Medicine, University of Brierley SM Adelaide • Nerve-Gut Research Laboratory, received the Young Investigator Award Elshaug A from the International Functional Brain-Gut Research Group • Public Health, Invited Delegate, High Flyers Think Tank on Preventative • Scholarship to attend the Young Investigator Meeting ‘Moving Forward in Health (Science and Technology in prevention and early detection of Neurogastroenterology and Motility’, 2nd Joint International Meeting of disease), University of Sydney, convened by the Australian Academy of Neurogastroenterology and Motility, Luzern, Switzerland Science with support of the UK Royal Society through the Theo Murphy Brown A (Australia) Fund • Acute Leukaemia Laboratory, received a Cancer Council SA Travel Grant Evdokiou A to attend the American Society of Hematology Meeting, San Francisco • Orthopaedic Bone Cell Biology Laboratory, promoted to Associate Burrell C Professor in the University of Adelaide • Virus Research Laboratory, awarded an AO in the Queen’s Birthday Eyre N Honours for service to medicine as a specialist in infectious diseases, • Hepatitis C Virus Research Laboratory, received an Australian Centre for particularly in the field of virology, as an administrator and educator, and HIV and Hepatitis Virology Travel Award to the community of SA through the establishment of the Coriole Music Fazzalari N Festival • Bone and Joint Research Laboratory, featured in the 2008 edition of the Butler L NH&MRC’s 10 of the Best (research projects) for his Healthy Ageing • Breast & Prostate Cancer Research Laboratories, awarded a Senior Research Grant entitled ‘Osteoarthritis: a community health issue and a Research Fellowship from The Cancer Council of South Australia vision to identify new diagnostic and treatment strategies’ Callen D Feltrin K • Breast Cancer Genetics, appointed Professor, University of Adelaide • Endocrine Research Laboratory, awarded PhD, ‘The Role of the Free Fatty • Appointed Postgraduate Coordinator, School of Medicine, University of Acid, Lauric Acid, in Appetite Regulation and its Potential as an Appetite- Adelaide Suppressant’ Cawrse J Gibson R • Breast Cancer Genetics, awarded BSc(Honours, First Class), ‘Investigation • Mucositis Research Group, Cancer Council South Australia recipient of of a Common Mechanism of Interaction Between Four Ankyrin Proteins Travel Grant to attend Multinational Association of Supportive Care in and p53’, Discipline of Medicine, University of Adelaide Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual • Received a Travel Bursary to attend the Lorne Cancer Meeting Scientific Meeting Goldney RD • Psychiatry, Chad Buckle Fellow, Wellington Clinical School, University of Otago and Capital and Coast Mental Health Services Suicide Prevention Initiative, Wellington, New Zealand

90 Annual Report 2008 Hanson Institute Proudly bringing together the best AWARDS, APPOINTMENTS AND ACCOLADES of South Australia’s medical research

Gordon E Iachini D • Lymphatic Development Laboratory, Highly Commended Poster Presenter, • Breast Cancer Genetics, awarded a Cancer Council Student Vacation Faculty of Health Sciences Postgraduate Expo, University of Adelaide Scholarship Greenwood J Jersmann H • Skin Engineering Laboratory, awarded the Australian Lions Children’s • Lung Research Laboratory, Teaching Award, University of Adelaide Mobility Foundation Silver Award Keefe D Gregory PA et al • Mucositis Research Group, elected President-Elect of the Multinational • Cytokine Research Laboratory, Hanson Institute Best Scientific Publication Association of Supportive Care in Cancer (MASCC) awarded to Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid Kleinig T G, Vadas MA, Khew-Goodall Y, Goodall GJ ‘The miR-200 family and miR- • Neuropathology Research Laboratory, Best Oral Presenter prize, Faculty of 205 regulate epithelial to mesenchymal transition by targeting ZEB1 and Health Sciences Postgraduate Medical Research Expo, University of SIP1’, Nature Cell Biology 10:593-601, 2008 Adelaide • Best Poster Award, 20th Lorne Cancer Conference Kok C Grimbaldeston M • Acute Leukaemia Laboratory, received an AMATA student travel bursary to • Cytokine Receptor Laboratory, won the Hanson Institute Basic Science attend the 8th Australasian Microarray and Associated Technologies New Investigator Award Association (AMATA) meeting, Dunedin, New Zealand Gronthos S Kopetz V • Mesenchymal Stem Cell Group & Regenerative Medicine Program, Bone • Adelaide Proteomics Centre, received a Poster Prize at the International & Cancer Laboratories, awarded NHMRC Senior Fellowship Level A HUPO conference, Amsterdam, The Netherlands • Co-Director, Centre for Stem Cell Research, University of Adelaide • Panel Member for NHMRC Grant Review Panel, Cell Biology Kumarasinghe D • Member of the Editorial Board for the Journal Stem Cells • Bone and Joint Research Laboratory, received The 2008 Healthy Ageing Harrington AM Research Cluster Best Poster Presentation, ASMR meeting • Nerve-Gut Research Laboratory, received a Travel Award to attend the 2nd Liew C-L Joint International Meeting of Neurogastroenterology and Motility, Luzern, • Lung Research Laboratory, awarded Master of Medical Science, University Switzerland of Adelaide Harvey N Liew G • Lymphatic Development Laboratory, invited representative of ANZSCDB at • Cardiovascular Research Laboratory, Highly Commended Poster Science Meets Parliament, Canberra Presenter, Faculty of Health Sciences Postgraduate Expo, University of Helbig K Adelaide • Hepatitis C Virus Research Laboratory, awarded the Qiagen Young Lin N-H Investigator Award Silver Medal Student Award at the 4th Australian • Mesenchymal Stem Cell Group & Regenerative Medicine Program, Bone Centre for HIV and Hepatitis Virology meeting, Barossa Valley & Cancer Laboratories, received an NHMRC Postgraduate Scholarship Hickling J Loo H-Y • Public Health, awarded Master of Public Health, University of Adelaide • Virus Research Laboratory, awarded 2nd class Honours, ‘ Production of ‘Tobacco Control Among People with Mental Illness’ HIV Neutralizing Antibodies’, University of South Australia Hiller J Low H-C • Public Health, Basil Hetzel Award for Leadership in Public Health, Public • Hepatitis B Virus Research Laboratory, received a Postgraduate Travel Health Association of Australia, South Australian Branch Award to attend the Molecular Biology of HBV Viruses Meeting, La Jolla, • Elected to the Board of Directors of Health Technology Assessment California International for a 3 year term Luscombe-March N Hodge G • Obesity Research Group, awarded a CCRE Postdoctoral Fellowship • Lung Research Laboratory, promoted to Associate Professor, University Manning J of Adelaide • Molecular Regulation Laboratory, awarded the Best Poster Presenter at the Hodge S Faculty of Health Sciences Postgraduate Expo • Lung Research Laboratory, promoted to Associate Professor, University McCartney E of Adelaide • Hanson Institute Clinical Investigator Award • Hepatitis C Virus Research Laboratory, received an Australian Centre for • Australian Lung Foundation/Webster COPD Research Award HIV and Hepatitis Virology Postgraduate presentation award • NHMRC Clinical Career Development Award (relinquished for Biomedical • Runner-up in the Poster Prize Competition School of Molecular and CDA) Biomedical Science Research Symposium, University of Adelaide • NHMRC Biomedical Career Development Award • Received a Postgraduate Travel Fellowship from the Health Science • RAH/SA Pathology Research Committee Florey Fellowship (relinquished Research Committee, University of Adelaide March 2008) Menicanin D • Nominated by, and represented NHMRC at ‘Science Meets Parliament’ • Mesenchymal Stem Cell Group & Regenerative Medicine Program, Bone • Honorary Editorial Board Member, Inflammation & Allergy – Drug Targets & Cancer Laboratories, received a Dawes Scholarship from the RAH/SA Hughes PA Pathology Research Committee • Nerve-Gut Research Laboratory, received a Travel Award to attend the 2nd • Highly Commended Poster Presenter, Faculty of Health Sciences Joint International Meeting of Neurogastroenterology and Motility, Luzern, Postgraduate Expo, University of Adelaide Switzerland • Awarded his PhD ‘Localisation and Function of Mechanosensory Ion Channels in Colonic Sensory Neurons’

91 Annual Report 2008 Hanson Institute Proudly bringing together the best AWARDS, APPOINTMENTS AND ACCOLADES of South Australia’s medical research

Miller D Quach M • Hepatitis B Virus Research Laboratory, awarded his PhD ‘Development of • Molecular Oncology Group, awarded an Honours 2A degree ‘Tumour Cell Novel Vaccine Strategies for Duck Hepatitis B Virus Infection’, School of Surface Proteins as Novel Antibody Targets for Circulating Tumour Cell Molecular and Biomedical Science, University of Adelaide Detection’, University of Adelaide • Received a Postgraduate Academic Achievement Award, School of Ramshaw H Molecular and Biomedical Science, University of Adelaide • Cytokine Receptor Laboratory, awarded a Peter Nelson Leukaemia Senior Moldenhauer L Research Fellowship from The Cancer Council South Australia • Experimental Therapeutics Laboratory, Highly Commended Poster Reaiche G Presenter, Faculty of Health Sciences Postgraduate Expo, University of • Hepatitis B Virus Research Laboratory, awarded her PhD ‘Characterisation Adelaide of the Events Involved in the Resolution of Acute Duck Hepatitis B Mundy L Virus Infection’, School of Molecular and Biomedical Science, University • Public Health, awarded Master of Public Health, University of Adelaide of Adelaide Does Australia Need a Horizon Scanning Network to Identify New • Received from Avexa Limited the Hepatitis Student Research Bronze Pharmaceuticals Entering the Market Place?’ Medal award, at the Australian Centre for HIV and Hepatitis Virology Need E Research Scientific Meeting, Barossa Valley • Breast & Prostate Cancer Research Laboratories, awarded her PhD Reed S Androgens and androgen receptor signalling in men’, University of • Public Health, awarded Bachelor of Health Science, Honours, University Adelaide of Adelaide ‘Was Public Health on the Agenda in Australia’s 2007 Federal Neilsen P election? An Examination of the Health Policies of the Major Political Parties, 2008’ • Breast Cancer Genetics, awarded his PhD ‘Functional Analysis of ANKRD11 and FBX031: Two Candidate Tumour Suppressor Genes from Reynolds P the 16q24.3 Breast Cancer Loss of Heterozygosity Region’, Discipline of • Lung Research Laboratory, elected as National Chairman, Specialist Medicine, University of Adelaide Training Committee in Respiratory and Sleep Medicine, Royal • Received a Travel Bursary to attend the Lorne Cancer Meeting Australasian College of Physicians • Abstract chosen as platform presentation at the Inaugural Sydney Cancer Sadras T Conference • Acute Leukaemia Laboratory, received a Leukaemia Foundation of Noordeen F Australia (LFA) Honours Scholarship • Hepatitis B Virus Research Laboratory, received from Integrated Sciences, • Received an Australian Postgraduate Award for 2009-2011 a Bronze Medal Student Award, at the Australian Centre for HIV and Sharma R Hepatitis Virology Research Scientific Meeting, Barossa Valley • Breast Cancer Genetics, awarded an International Union Against Cancer Ochnik A (UICC) Yamagiwa-Yoshida Memorial International Cancer Study Grant • Breast & Prostate Cancer Research Laboratories, awarded the Best Poster Smith L Presenter prize at the Faculty of Health Sciences Postgraduate Expo, • Bone and Joint Research Laboratory, awarded PhD with commendation, University of Adelaide University of Adelaide ‘Structure and Function of the Elastic Fibre Network • Awarded the Best Commercial Poster Presenter prize by ARI Pty Ltd at the of the Human Lumbar Annulus Fibrosus’ Faculty of Health Sciences Postgraduate Expo Soo ML Page AJ • Virus Research Laboratory, awarded First Class Honours, ‘Investigating • Nerve-Gut Research Laboratory, awarded an Abstract of Distinction, Joint the Role of GRP78 During Dengue Virus Infection’, University of Adelaide International Meeting on Neurogastroenterology and Motility Stringer A Papadopoulos A • Mucositis Research Group, Cancer Council South Australia recipient of • Bone and Joint Research Laboratory, awarded Honours, University of Travel Grant to attend Multinational Association of Supportive Care in Adelaide ‘The Role of the Osteocytic Cell Network in Bone Remodelling’ Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Paterson EL Scientific Meeting • Cytokine Research Laboratory, Best Poster Award, University of Adelaide • Faculty of Health Sciences Postgraduate Travelling Award Faculty of Health Sciences Postgraduate Expo 2008 Tallis P Peters A • Breast Cancer Genetics, awarded a Faculty of Health Sciences • Breast & Prostate Cancer Research Laboratories, awarded her PhD Undergraduate Research Scholarship Androgen Signalling in Normal and Malignant Breast Epithelial Cells’, Thomas D University of Adelaide • Cytokine Receptor Laboratory, received the 2008 Royal Australasian Pilichiewicz A College of Physicians Trainee Research Award for Adult Medicine at the • Endocrine Research Laboratory/Obesity Research Group, awarded PhD RACP Congress, Adelaide (equal award with a trainee from New South ‘Factors Involved in the Regulation of Gastrointestinal Motility, Hormone Wales) Release, Symptoms and Energy Intake in Health and Patients with Tilley W Functional Dyspepsia’ • Breast & Prostate Cancer Research Laboratories, awarded the Ron Ross Psaltis P Award (for contributions to breast and/or prostate cancer research and • Cardiovascular Research Group/Mesenchymal Groups, awarded the Best mentoring younger scientists), 4th PacRim Breast and Prostate Cancer Poster Presenter prize at the Faculty of Health Sciences Postgraduate Meeting, Whistler, British Columbia Expo, University of Adelaide

92 Annual Report 2008 Hanson Institute Proudly bringing together the best AWARDS, APPOINTMENTS AND ACCOLADES of South Australia’s medical research

Trahair H • Hepatitis B Virus Research Laboratory, awarded his Bachelor of Science Degree, Second Class Honours ‘Understanding and Optimising Prime- Boost Vaccination Strategies’, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide Tu T • Hepatitis B Virus Research Laboratory, received from the Australian Society of Microbiology, South Australian Branch, a Student Travel Award to attend the Annual Scientific Meeting of the Australian Society for Microbiology, Perth, 2009 Wang C • Hepatitis B Virus Research Laboratory, awarded her Bachelor of Science Degree, First Class Honours ‘Toll-Like Receptors and the Early Events During Duck Hepatitis B Virus Infection’, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide Wati S • Virus Research Laboratory, awarded her PhD ‘Altered Responses of Dengue Virus Infected Cells to TNF-Alpha and Induction of GRP78 and HSP70 – In Vitro Studies’, University of Adelaide Wendland A • Viral Epidemiology Laboratory, awarded her Bachelor of Science Degree, Honours, ‘Development of a Cell Culture System for Adelavirus, a Novel Member of the parvovirinae. White D • Melissa White Leukaemia Research Laboratory/ Myeloma & Mesenchymal Research Group awarded her PhD, University of Adelaide ‘Factors Which Impact on the Response of CML Patients to ABL Kinase Inhibitor Therapy: A Study of Imatinib and Nilotinib’ Williams D • Cell Signalling Networks Laboratory, received a second year poster prize, University of Adelaide Williams S • Molecular Signalling Laboratory, received Best Poster Award, Queenstown Signal Transduction Meeting, Queenstown, New Zealand Wittert G • Obesity Research Group, Finalist in the Premiers Science Award – Public Good category • Invited to participate in the 2020 Summit, Canberra • Independent Chair of the Weight Management Council of Australia Xia X • Lung Research Laboratory, awarded PhD ‘Gene Therapy for Mesothelioma: Studies of Conditionally Replicative Adenoviruses and Measles Virus’, University of Adelaide Xiong J • Mesenchymal Stem Cell Group & Regenerative Medicine Program, Bone & Cancer Laboratories, awarded a University of Adelaide International Scholarship Zhang D • Public Health, awarded PhD, ‘HIV/AIDS Behavioural Surveillance Among Men Who Have Sex with Men in China – Community and Internet Based Surveys’, University of Adelaide Zinonos I • Bone Cancer Research Group, Orthopaedics Laboratory, Highly Commended Poster Presenter, Faculty of Health Sciences Postgraduate Expo, University of Adelaide • Best Honours Oral Presentation, ASMR meeting

93 Annual Report 2008 Hanson Institute RESEARCH STAFF Proudly bringing together the best of South Australia’s medical research Hanson Institute and Affiliated Laboratories

ACUTE LEUKAEMIA Project Officers Students CELL GROWTH AND LABORATORY Leah McWilliams Miriam Butler DIFFERENTIATION Member Alison Wigg Sarah Carter LABORATORY Richard D’Andrea Graduate Students Margaret Centenera Member HuiQin Chiam Scientific Staff Michaelia Cockshell Mark Guthridge Shalini Jindal Anna Brown Serene Chng Scientific Staff Eleanor Need Carolyn Butcher Nicholas Eyre Emma Barry Aleksandra Ochnik Lena Erikkson Anita Lee Ana Lonic Amelia Peters Clementine Menz Nicholas Mabarrack Jason Powell Andrew Trotta Petra Neufing Wei-Chun Tu Astrud Tuck Students Michelle Perugini BONE AND JOINT RESEARCH Yang Kong BREAST CANCER GENETICS Diana Salerno LABORATORY Daniel Thomas LABORATORY Students Member Nhan Truong Member Sonya Diakiw Nick Fazzalari CELL REGULATION NETWORKS David Callen Chung Kok Scientific Staff LABORATORY Teresa Sadras Scientific Staff Arash Badiei Associate Member Xin Shi Paul Neilsen John Codrington Joanna Woodcock ADELAIDE CENTRE FOR Julia Humphries Renee Schulz Scientific Staff SPINAL RESEARCH Sladjana Jovcic Raman Sharma Carl Coolen Julia Kuliwaba Students Emeritus Member Yuefang Ma Vivienne Le Jacqueline Cawrse Barrie Vernon-Roberts Yeap Shien Ng Ian Parkinson Zarqa Saif Member Students Egon Perilli CARDIOVASCULAR RESEARCH Robert Moore Kay Anantanawat Shruti Shah GROUP Scientific Staff Lachlan Smith Danielle Williams Members David Ardern Peter Sutton-Smith CELL SIGNALLING Prashanthan Sanders Bernice Gutschmidt Lena Truong LABORATORY Jomick Lumawig Stephen Worthley Helen Tsangari Associate Member Peter McNeil Scientific Staff Students Yeesim Khew-Goodall Adam Meir Angelo Carbone Christopher Bates Adnan Mulaibrahimovic Georgy Chako Scientific staff Andrew Chang Ai-Quoc Phan Nguyen Rajiv Das Lesley Crocker Duminda Kumarasinghe Silvana Pinneri Douglas Kelly Albert Leung Students Martin Wilby Pawel Kuklik Geetha Mohan Leila Wyatt Reza Zarrinkalam Lorraine Mackenzie Sheng La Wu Samuel Dyer Students Adam Nelson BREAST AND PROSTATE CENTRE OF CLINICAL Andrew Fagan Cynthia Piantadosi CANCER RESEARCH RESEARCH EXCELLENCE IN Sladjana Jovcic Kean Soon LABORATORIES NUTRITIONAL PHYSIOLOGY, Maida Mulaibrahimovic Karen Teo INTERVENTIONS AND Benjamin Rogers Members Kerry Williams OUTCOMES Villis Marshall Lauren Wilson ARTHRITIS AND Wayne Tilley Dennis Wong Investigators RHEUMATOLOGY RESEARCH Matthew Worthley Ashley Blackshaw LABORATORY Associate Members Chris Rayner Lisa Butler Glenn Young Members Christine Feinle-Bisset David Horsfall Students Leslie Cleland Christopher Nordin. Angelo Carbone Michael James Scientific staff Elizabeth Beckett Ben Dundon Graham Mayrhofer Tina Bianco-Miotto Gary Wittert Grant Buchanan Aaron Farquharson Ian Chapman Scientific staff Margaret Centenera Gary Liew Jane Andrews Gillian Caughey Elisa Cops Payman Molaee Karen Jones Rebecca Cook-Johnson Theresa Hickey Adam Nelson Manny Noakes Sarah Downie-Doyle Helen Hughes Cynthia Piantadosi Michael Horowitz Cindy Hall Silke Kantimm Peter Psaltis Peter Clifton Susan Lester Tanja Karasoulos Rishi Puri Richard Holloway Robert Metcalf Ean Phing Lee Kurt Roberts-Thomson Robert Fraser Mahin Moghaddami Sook Ching Lee Ross Roberts-Thomson Llewellyn Spargo Kelvin Wong Postdoctoral Fellows Eleanor Need Natalie Luscombe-Marsh Contributing Medical Officers Michelle Newman Student Researchers Richard Young Catherine Hill Melissa O’Loughlin Mauayad Alasady Pamela Johal Amelia Peters Yanzhenzi Dai Postgraduate Students Anita Lee Marie Pickering Tim Greenwell David Jesudason Vidya Limaye Carmela Ricciardelli Sean Jolly Eva Pedersen. Peter Penglis Vanessa Thompson Suchi Karuna Lora Vanis Susanna Proudman Joanna Treloar Darryl Leong Paul Cavuoto Maureen Rischmueller Margaret Yard Han Sung Lim Sujitha Thavapalachandran Christopher Wong

94 Annual Report 2008 Hanson Institute RESEARCH STAFF Proudly bringing together the best of South Australia’s medical research Hanson Institute and Affiliated Laboratories

Support Staff Scientific Staff Scientific staff Clinical Trials Unit Tim Murphy (Project Officer) Paul Anderson Adhra Al-Mawali Kirsty Herewane Kylie Lange (Biostatistician) Prem Dwivedi Alex Collella Jenny McGrath Judith Wishart (Technical Officer). Alison Moore Pam Dyson Mary McAlister CYTOKINE RECEPTOR Rebecca Sawyer Trevor Rawling Louise Milazzo LABORATORY Juliette Tyson Judy Stevens Sue Malik Rick Tocchetti Member Students Students Michael Vo Angel Lopez Alice Lee Wei Xia Nga Lam Student Chien-Li Liew Scientific Staff Smita Hiwase Lisa Biggs ENDOCRINE RESEARCH LYMPHATIC DEVELOPMENT Mara Dottore LABORATORY HEPATITIS B VIRUS RESEARCH LABORATORY Michele Grimbaldeston Associate Member LABORATORY Associate Member Timothy Hercus Christine Feinle-Bisset Associate Member Natasha Harvey Rebecca Krake Students Allison Jilbert Scientific Staff Barbara McClure Erin Bollmeyer Scientific staff Jan Kazenwadel Melanie Pudney Ixchel Brennan Behzad Baradaran Students Hayley Ramshaw Radhika Seimon Dieu-Lien Dang Kelly Betterman Anna Sapa EXPERIMENTAL Feng Feng Emma Gordon Tetyana Shandala Arend Grosse THERAPEUTICS LABORATORY MEDICAL ONCOLOGY Frank Stomski Eric Qiao Member CLINICAL RESEARCH Olga Sukocheva Georget Reaiche (from August Michael Brown Elena Zaporoshenko 2008) Members Students Associate Member Catherine Scougall Michael Brown John Hayball Dorothy Keefe Jarrod Sandow Students Chris Sweeney Daniel Thomas Scientific staff Huey-Chi Low CYTOKINE RESEARCH Fares Al-Ejeh Faseeha Noordeen Clinicians LABORATORY Jocelyn Darby Georget Reaiche (until July 2008) Michael Brown Kerrilyn Diener Dorothy Keefe Member Michael Thorpe Anastasia Yu Richard Logan Greg Goodall Chee Quin Toeh Students Hugh Trahair Anne Taylor Scientific staff Emma Beukema Thomas Tu Nimit Singhal Andrew Bert Cara Fraser Cuixia Wang Sid Selva-Nayagam Cameron Bracken Erin Curry Chris Sweeney Philip Gregory HEPATITIS C VIRUS RESEARCH Behavioural Scientist Emily Verrier GASTROENTEROLOGY LABORATORY RESEARCH LABORATORY Hayley Whitford Students Associate Member Clinical Trials Manager Natasha Kolesnikoff Associate Member Michael Beard Nancy Olszewski Emily Paterson Andrew Ruszkiewicz Scientific staff Daniel Thomson Scientific staff Karla Helbig Clinical Trial Coordinators Toni Marafioti DRUGS AND METALS Maria Caruso Nicholas Eyre Melinda Whelan RESEARCH LABORATORY Ha Tran Gorjana Radisic Satiya Wati Sophie Robertson Affiliate Members Technical staff Evelyn Yip Wendy Schwerdt Peter Coyle Kay Taylor Clinical Trials Nurses Allan Rofe HAEMATOLOGY CLINICAL Students Rennee Phillips Michelle Hawkin Students RESEARCH UNIT Erin McCartney Anne Marie Halligan Joanne Chua Member Clinical Trial Assistants Brooke Summers L Bik To LUNG RESEARCH LABORATORY Hazel Bourke ENDOCRINE AND METABOLIC Affiliate Member Joanne Rosmini UNIT Ian Lewis Member Paul Reynolds Oral Pathologist Member Haematologists Richard Logan David Torpy Peter Bardy Associate Member Post-Doctoral Scientists Pratyush Giri Sandy Hodge Student Rachel Gibson Noemi Horvath Affiliate Member Lucia Gagliardi Joanne Bowen John Lloyd Mark Holmes ENDOCRINE BONE RESEARCH Andrea Stringer Simon McRae Scientific staff LABORATORY Student Nigel Patton Jessica Ahern Member Noor Al-Dasooqi Lay Tay Michael Djukic Howard Morris Clinical Trial Coordinators Greg Hodge External Member Lisa Carne Hubertus Jersmann Brian May Kylie Chaplin Geoff Matthews Associate Member Bronwen Cox Ann Reynolds Peter O’Loughlin Chris Hoare Krishna Sriram Tania Lewis Joseph Tan Che To

95 Annual Report 2008 Hanson Institute RESEARCH STAFF Proudly bringing together the best of South Australia’s medical research Hanson Institute and Affiliated Laboratories

MELISSA WHITE LEUKAEMIA Students MYELOMA AND Bernice Gutschmidt RESEARCH LABORATORY Georgia Arentz MESENCHYMAL RESEARCH Stephen Helps Member Mark Cutting GROUP Sven Kambuts Timothy Hughes Amanda Gysbers Associate Member Barbara Koszyca Meeiying Quach Jim Manavis Scientific staff Andrew Zannettino Kathryn Rodgers Stephanie Arbon Clinical Associates Scientific staff Grace Scott Bronwyn Cambareri Peter Bardy Peter Diamond Renee Turner Phuong Dang Peter Hewett Andrea Dewar Corinna Van Den Heuvel Laura Eadie Tim Price Amanda Farrugia Kelvin Groot Obbink Nick Rieger Panagiota (Penny) Kostakis Students Verity Saunders Amanda Townsend Sharon Paton Christine Barry Amity Venables MOLECULAR REGULATION Jenny Drew Naomi Cook Sasha Wheeler LABORATORY Sharon Hampton-Smith Frances Corrigan Levon Gabrielian Deb White Member Students Tim Kleinig Stephanie Zrim Sharad Kumar Li Fei (Lisha) Bong Rowena Newcombe Students Jane Englar Scientific staff Emma Thornton Stephen Blake Deb Harland Natasha Boase Tuyet Tran Jane Engler Dimitrios Cakouros Carmen Macsia OBESITY RESEARCH GROUP Devendra Hiwase Zoe Campbell Sally Martin David Ross Joel Castro Peter Psaltis Member Carine Tang Hazel Dalton Kate Vandyke Gary Wittert MESENCHYMAL STEM CELL Donna Denton NERVE-GUT RESEARCH Research Officers GROUP AND REGENERATIVE Loretta Dorstyn LABORATORY George Hatzinikolas MEDICINE PROGRAM Natalie Foot Members Sean Martin Member Lien Ha Ho Ashley Blackshaw Clinical Research Manager Stan Gronthos Yewann Leong John Dent Kerry Kristaly Kathryn Mills Scientific staff Gerald Holtmann Dietician Alicia Paterson Agnieszka Arthur Scientific staff Jane Mudge Sonia Shalini Tanyia Henshall Birgit Adam Robyn Taylor Research Nurse Sandra Isenmann Jane Andrews Scott Townley Ms Leanne Owen Krzysztof Mrozik Stuart Brierley Post Doctoral Fellows Sharon Paton Students Nicole Cooper Alena Janovska Naohisa Wada Zoe Kilpatrick Claudine Frisby Cynthia Piantadosi Jantina Manning Andrea Harrington Students Natalie Luscombe-Marsh MOLECULAR SIGNALLING Richard Holloway Lochlan Cooper Amelia Pilichiewicz Ni-Hung Lin LABORATORY Patrick Hughes Students Sally Martin Member Heather Lyman Paul Cavuoto Rosa McCarty Stuart Pitson Tobias Liebregts Chris Martin Yan Lam Danijela Menicanin Scientific staff Melissa Moretta Lisa Philp Peter Psaltis Renae Barr Tracey O’Donnell OPHTHALMOLOGY RESEARCH Jimin Xiong Julia Dobbins Amanda Page LABORATORY MICROBIOLOGY RESEARCH Briony Gliddon Jenny Persson AND DEVELOPMENT Ruby Ivanov Associate Member MingXian Yang LABORATORY Paul Moretti Robert Casson Richard Young Associate Member Melissa Pitman Scientific staff Students Michael Heuzenroeder Samantha Williams Glyn Chidlow Jonathan Coldwell Students Mark Dayman Scientific staff Montri Gururatsakul Kate Jarman Michael Schober Ian Ross Steven Kentish Tamara Leclercq John Wood Students Nektaria Pezos Angus Magarey Tuet Wong Sophia Tan Amy Sanguesa Duyen Pham Students Chun Chun Young James Slattery MUCOSITIS RESEARCH Andreas Ebneter MOLECULAR ONCOLOGY Kate Sutherland GROUP Bruce Heidemann GROUP NEUROPATHOLOGY RESEARCH Matthew Holman Member Affiliate Member LABORATORY Sarabjit Saggu Dorothy Keefe Jennifer Hardingham Members ORTHOPAEDIC BONE CELL Scientific staff Staff Peter Blumbergs BIOLOGY LABORATORY Joanne Bowen Yin Ying Ho John Finnie Rachel Gibson Member Michael Rayner Tim Kuchel Andrea Stringer David Findlay Joseph Wrin James Temlett Richard Logan Philip Thompson Associate Member Students Robert Vink Gerald Atkins Ann Suk Jing Yeoh Scientific staff Scientific staff Andrea Stringer Zhao Cai Christina Vincent Noor Al-Dasooqi Kathy Cash Katie Welldon Yvonne Ciuk Asiri Wijenayaka

96 Annual Report 2008 Hanson Institute RESEARCH STAFF Proudly bringing together the best of South Australia’s medical research Hanson Institute and Affiliated Laboratories

Student RENAL RESEARCH Technical Staff LIQUID NITROGEN FACILITY Duminda Kamarasinghe LABORATORY Sarah Catalano Manager Visiting Fellow Member Bronwen Mayo Tony Cambareri Masakazu Kogawa Randall Faull Student Scientific Staff ORTHOPAEDICS AND TRAUMA Associate Member Annika Wendland David Tregear RESEARCH Chen Au Peh VIRUS RESEARCH MAbSA LABORATORY Member Scientific Staff Manager Donald Howie Plinio Hurtado Member Alfio Comis Lisa Jeffs Christopher Burrell Scientific staff Scientific Staff Jodie Nitschke Stuart Callary Affiliate Member Linda Bourne Tania Carbone Student Peng Li VETERINARY SERVICES Snezana Cerovina Nicole Pontin Scientific Staff DIVISION Kerry Costi Renal Unit Clinical Trials Mohammed Alsharifi Members Maria Costi group Jill Carr John Finnie Melina Dalese Anna Hooper Tuckweng Kok Tim Kuchel Angie Fassina Kim Milde Darren Miller (to June 2008) Oksana Holubowycz Alison Napier Saw-Yin Oh (part-time) Affiliate Member Tania Knight Ky-Lee Pirone Adrian Purins (part-time) Allan Rofe Margaret McGee Frances Skilton Students Scientific Staff Susan Neale SKELETAL MALIGNANCIES Huey-Yeng Loo Dorota Gancarz Susan Pannach RESEARCH GROUP, Sarah Martin Annabel Good Roumen Stamenkov ORTHOPAEDICS & TRAUMA Adrian Purins (part-time) Marianne Lim Corinna Wildenauer DISCIPLINE Mei-Ling Soo Andrew Menelaou Visiting Fellows Susan Porter Associate Member Satiya Wati William Martin Amy Stuchbery Andreas Evdokiou CORE FACILITIES Timothy Kain Richard Turnbull Scientific staff ADELAIDE MICROARRAY Students Evana Wade Shelley Hay CENTRE Stuart Callary Agatha Labrinidis ZhenHai Gu Member Vasilios Liapis Roumen Stamenkov Greg Goodall Aaron Stevenson Students Scientific Staff Ioanne Vakaki Michelle Lee Rosalie Kenyon Irene Zinonos PATHOLOGY LABORATORY Mark Van der Hoek SKIN ENGINEERING Affiliate Member ADELAIDE PROTEOMICS LABORATORY Leon Bignold CENTRE Associate Member PSYCHIATRY GROUP Associate Members John Greenwood Chris Bagley Member Scientific Staff Peter Hoffmann Robert Goldney Bronwyn Dearman Scientific Staff PUBLIC HEALTH GROUP Amy Li Alex Colella Member VASCULAR BIOLOGY AND Chris Cusaro Janet Hiller CELL TRAFFICKING Sandra Hack Scientific Staff LABORATORY Megan Retallick Adam Elshaug Associate Member Students Students Claudine Bonder Hayley Andreazza Olga Anikeeva Scientific staff Yadollah Bahrami Cathy Chittleborough Jeffrey Barrett Julie Brazzatti Hasan bin Hamza Wai Yan Sun Marc Condina Tracy Merlin Michaelia Cockshell Johan Gustafsson Caroline Miller Anna Sapa Victoria Kopetz Chris Morris Samantha Escarbe Tomas Koudelka Jacci Parsons Student DETMOLD FAMILY IMAGING Siobhan Reed Shaundeep Sen FACILITY Tim Schultz Manager Victoria (Tori) Wade VIRAL EPIDEMIOLOGY Tony Cambareri Dapeng Zhang LABORATORY Associate Member Scientific Staff Rodney Ratcliff Alan Bishop Sandy MacIntyre Scientific Staff Katherine Pilkington Jane Arthur Ghafar Sarvestani Feng Gao Jing Ou En-Chi Wan

97 Annual Report 2008 Hanson Institute Proudly bringing together the best MANAGEMENT AND ADMINISTRATION of South Australia’s medical research

Advisory Board (until 30th June 2008) Intellectual Property and Commercialisation Office Mr Graham Spurling Bernadette Swart Inaugural Chairman IP & Commercialisation Manager Mr Kevin Kelly Elizabeth Holland-Clarke IMVS Council Chairman Senior Commercial Lawyer Professor Brendon Kearney Belinda Wade IMVS Director Business Development Associate Ms Virginia Deegan Craig Rogers RAH General Manager Business Development Associate Professor Howard Morris Daniela Tyson Director of the Hanson Institute Intellectual Property Officer Professor Bik To Dara Melanson Chair, RAH/IMVS Research Committee Intellectual Property Officer Hanson Institute Executive Committee (until 30th June 2008) Elena Voss Intellectual Property Administration Officer part-time Professor Brendon Kearney Director, IMVS RAH Research Fund Professor Howard Morris Mr Mark Goldsmith Director, Hanson Institute Fundraising Manager Professor Peter Blumbergs Mr Peter Choat Head, Hanson Institute Centre for Neurological Diseases Bequest Officer Professor David Findlay Media and Public Relations Head, Orthopaedic Bone Cell Biology Laboratory Mr David Walsh Professor Wayne Tilley Manager, Marketing, Media and Public Relations Head, Dame Roma Mitchell Cancer Research Laboratories Hanson Institute Executive Committee (until 30th June 2008) Professor Bik To Chair, RAH/IMVS Research Committee Professor Justin Beilby Executive Dean, Faculty of Health Science, University of Adelaide Directorate Professor Howard Morris Director Associate Professor Peter Coyle Chief Operating Officer Brendon Kearney Howard Morris Ms Charmain Rogers Financial Adviser Mrs Mari Walker Executive Assistant Hanson Clinical Research Centre Ms Caroline Rawling Clinical Research Manager until 15th September 2008 Ms Jenny Latte Peter Blumbergs David Findlay from 1st December 2008 Research Secretariat Ms Anna Varga Manager until 25th July 2008 Ms Renalyn Roxas Acting Manager from 4th August 2008 Ms Kathryn Zagrodzki Administrative Officer Ms Tara Pearson Wayne Tilley Bik To Human Resources Officer Ms Rose Winkler Administrative Officer

Justin Beilby

98 Annual Report 2008 Hanson Institute Proudly bringing together the best CONTRIBUTORS TO THE HANSON INSTITUTE of South Australia’s medical research

Direct donations to the Hanson Institute provide essential Bequests resources mainly for infrastructure such as equipment and Estate of Jessie Geraldine Ferguson laboratories. We are extremely grateful for each and every Estate of Peter N Fleming one of these donations. Estate of Marlene E Green Life Members Estate of Mary Hanlon Mr R Gerard AO Estate of Ronda I Henderson Mrs F Gerard AO Estate of Joyce Higson Mr G Pickard AM Estate of Leonard A Hill Major Benefactors Estate of Maud F Kellett Mr L J Balchin (Dec) Estate of Edna E McManus Fay Fuller Foundation Pty Ltd Estate of Katharina Nakonecznyj Julian Burton Burns Trust Estate of John S Ryan Lions Medical Research Foundation Inc Estate of Priscilla Bessie Southgate Living To Beat Cancer Estate of Theresia Uncsik Melrose Health Supplies Estate of Lillian Waterhouse San Remo Macaroni Company Pty Ltd Estate of Kenneth D Wharton Shahin Charity Trust Estate of Graham Willington Benefactors Estate of Alfreda Zyzniewska Bank SA Staff Charitable Fund CSL Limited Mr Donald Dixon – Cans for Cancer Mr & Mrs Des & Eleanor Goedecke Mr Michael Hall HOSPIRA Australia Mrs Valerie King Mrs Alison J Kinsman AM Mrs A B Mellor Millicent Cancer Support Group Mount Gambier Country Concert Mr George Southgate Mr Gary Stiliano Mr Allen Thornton Top of the Torrens Theatre Group Associates ATCA Incorporated Alcon Australia Miss Rose Aldersey Mrs Margaret Angove Australian Carpet & Tile Company Mr Lewis Barrett AO Mr & Mrs B E & D M Bill Mr Carl Bridgman CMV Foundation Inasmuch Mr Theo Kappeler Mr & Mrs T J & R J McInerney McMahon Services Mount Gambier Breast Cancer Luncheon Group Murray F Young & Associates Mr Alan Shadgett The Le Cornu Group Miss HE Tucker

99 Annual Report 2008 Hanson Institute Proudly bringing together the best RESEARCH FUND REVIEW of South Australia’s medical research

Fund raiser

08 $3,968,991

07 $3,096,979

06 $3,068,592

05 $2,700,000

04 $834,895

0 1234 $ millions

Over the last 12 months the RAH Research Fund continued to help raise philanthropic gifts for crucial equipment for medical research whilst raising public awareness for the Hanson Institute. Collectively donors have contributed $3,968,991, an increase of $872,012 on the previous year. We wish to thank all of the generous people in the community who have chosen to support medical research via the RAH Research Fund. We also pay special respect and thanks to those people who have provided for medical research in their Will and through memorial gifts. As in previous years we have received wonderful support from our band of community fundraisers and we warmly acknowledge the following; • Paul and Irene Caines – Gambier Country • Donna Dias and Lulla Yiallourous – Kransky BBQ evenings • Mary Tarzia – Faith Hope & Charity Dinner • Cindy Najar and Kerry Woolston – Riverland Living to Beat Cancer Appeal. • Don Dixon – Cans for Cancer. • Gloria Seymour and The Strolling Tones. Financial Summary – 2008 • Polly & Brian Goodburn Income • Lillies for Leukaemia Committee Special Events $108,337.82 • Maria Marinos Commercial Operations $188,671.21 • Ted Carlaw and Ken Duplock Tee Off Fore Life Without Cancer Golf Day. Lotteries $8,779.00 Appreciation to both San Remo Macaroni Company and the Fay Fuller Fundraising $2,698,233.27 Foundation for their ongoing support of two Research Fellows and the funding of two new Training Fellowships within the Hanson Institute. Bequests $964,969.91 Total Income $3,968,991.21 The management and staff of the RAH Research Fund and Hanson Institute were saddened with the sudden passing of Aldo Crotti OAM, Executive Expenditure Chairman, San Remo Macaroni Company. Aldo was the Patron of the Salaries $304,065.88 successful RAH Development Appeal and benefactor to the Hanson Institute. Goods & Services $265,433.12 He was a South Australian icon and philanthropist who will be truly missed. Total Expenditure $569,499.00 The 2008 Community Outreach Program continued to build upon the Net Profit $3,399,492.21 awareness generated by the 2007 program and attracted a further 2,144 new supporters and raised $98,723 for medical research. Health and medical research is a changing and dynamic environment. Over the last 12 months $1,967,313 was provided to the Hanson Institute The consistent debate surrounding the location of the proposed new hospital which included in excess of $758,000 for equipment that included; and research facilities will present new challenges which we look forward to meeting. The impact of the global financial outlook will also provide for • Nanozoomer $75,000 interesting times for philanthropic giving. • Refrigerated Centrifuge $25,000 The Research Fund would also like to acknowledge our office volunteer • Real Time PCR Machine x 3 $107,651 staff, Maureen Goodwin, Marjorie Murray-Bonici and Kit Stevens, for their • Microscope Accessories $10,000 generous support. We would be lost without them. In addition thanks to • Chemiluminescent Machine $17,500 my outstanding team in Dianne Brock, Peter Choat, Jane Favretto, Michelle Robb and Alexia Rocha and welcome Kristina Vonow, our new Hanson tours once again proved very popular with donors. It gave Communication and Grants Officer. supporters a first hand look at how their donations were being applied and a better understanding of the breadth of world class research being Mark Goldsmith performed by some of the State’s brightest minds. Fundraising Manager

100 Annual Report 2008 How you can support the

THE HANSON INSTITUTE, incorporating the Centre for Cancer Research, Centre for Bone and Joint Research, Clinical Research Centre, Centre for Neurological Diseases and Centre for Biomedical Research was established with substantial assistance from the corporate and general communities of South Australia. The ongoing support of many of these groups and individuals ensures that quality research is able to continue.

THE CONTINUED SUCCESS of the Hanson Institute’s staff in achieving grant funding means that funds are continually required to support the extension of laboratory space, the purchase of equipment and ongoing training and development. How we use donated funds THE ROYAL ADELAIDE Hospital Research Fund actively seeks support from the community for the world class research that is being conducted at the Hanson Institute. All donations are used to support research and are not directed towards administrative costs. We will be pleased to honour your wishes to direct your donation to a particular field of research or, if you wish, to distribute it on your behalf to research areas of need and consistent with the Institutes programs. How to Support the Hanson Institute GIFTS OF any size will be acknowledged and recognised appropriately. Depending on the size of your generous gift and nature of the donation it may be in your interest to obtain financial advice.

Types of Support Organisation of Special Events For further information, please There are several ways you can If you would like to organise an contact The Manager, RAH support our research. event to benefit the Hanson Research Fund Institute, we will be happy to work North Terrace Individual Gifts with you. Please contact the RAH Adelaide The Research Fund is a Designated Research Fund Office. South Australia, 5000 Gift Recipient (DGR). Donations Telephone: (08) 8222 5281 $2 and over are tax deductible. Bequests, Legacies and other forms of Deferred or Planned Cheques should be made Memorial Gifts Giving: For help and support payable to the Hanson Institute All gifts will be acknowledged and please contact the Planned Giving and forwarded C/o the RAH the next of kin will be notified of the Officer in the RAH Research Research Fund names of people who have made Fund Office. Sheridan Building a memorial gift. North Terrace We would like thank all our donors “There is no finer way to Adelaide for their wonderful generosity which remember those who were near South Australia, 5000 continues to support important and dear to us than by helping research at the Hanson Institute that to give health, and perhaps life will ultimately benefit thousands of itself, to those who remain” people in Australia and overseas. Mr Mark Goldsmith (Fundraising Manager)

Proudly bringing together the best of South Australia’s medical research

101 Annual Report 2008 Hanson Institute Proudly bringing together the best NOTES of South Australia’s medical research

102 Annual Report 2008 Hanson Institute Proudly bringing together the best NOTES of South Australia’s medical research

103 Annual Report 2008 Hanson Institute Proudly bringing together the best NOTES of South Australia’s medical research

104 Annual Report 2008 Design Sue Dyer Design

Coordination Mari Walker/Mark Fitz-Gerald

Editor Peter Coyle

Advising Editor Mark Fitz-Gerald

Photography Peter Dent, Peta Grant and Mark Fitz-Gerald

Word Processing Mari Walker

Printing Finsbury Green Proudly bringing together the best of South Australia’s medical research