Wayne Tilley

Professor Wayne Tilley

Director - Dame Roma Mitchell Cancer Res Lab

Adelaide Medical School

Faculty of Health and Medical Sciences

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

Professor Tilley is the inaugural Chair of the Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide (2002- current). His research program is broadly focussed on hormonal carcinogenesis, with an emphasis on mechanisms of sex hormone signalling and the emergence of resistance to hormonal therapies used in the treatment of breast and prostate cancer. An undergraduate of the University of Adelaide, he subsequently completed a PhD at Flinders University in Adelaide and then was awarded an NHMRC CJ Martin Fellowship to undertake postdoctoral studies at UT Southwestern in Dallas, Texas, USA, where he cloned the human androgen receptor (AR). He returned to Flinders University in the early 1990s, where he established an independent breast and prostate cancer research program. In collaboration with the Head of Surgery, Professor Villis Marshall, Prof Tilley established the Flinders Cancer Centre at Flinders University / Flinders Medical Centre in the mid 1990’s. During that time at Flinders University he developed an internationally recognized research program on sex steroid hormone action in breast and prostate cancer, making a major contribution to understanding mechanisms of resistance to endocrine therapies. His research has demonstrated the oncogenic potential of the AR in prostate cancer and, conversely, a tumour suppressor role in breast cancer. A current major research focus is the development of novel AR target therapies for both cancers. In prostate cancer, this involves the generation of novel drugs to inhibit constitutively active AR variants that lack the ligand binding domain and are unresponsive to conventional androgen deprivation therapies. In the case of breast cancer, his research has led to new strategies to activate the AR and inhibit the growth of tumours that are driven by estrogen receptor alpha (ER). More recently, his research has highlighted the importance of cross-talk between progesterone, androgen and estrogen receptors in breast cancer to modulate disease outcomes.Prof Tilley convenes the International Breast and Prostate Cancer PacRim Meeting series, and was the recipient of the University of Adelaide’s 2015 Executive Dean’s Award for Research Excellence and the Endocrine Society of Australia 2016 Senior Plenary Award. He recently gave the introductory Plenary Lecture at the 2016 International Congress of Endocrinology in Beijing, China.

Major scientific contributions. My research has spanned more than 30 years, with a strong focus on sex hormone action, in particular androgen action, in breast and prostate cancer. This includes the original cloning of the androgen receptor (AR; PNAS 1989), demonstration that mutations in the AR gene are functionally important in breast and prostate cancer, and proving the oncogenic potential of AR in prostate cancer (Clin Cancer Res 1996; Cancer Res 2005; PNAS 2005). Conversely, my research has revealed a tumour suppressive function of AR in estrogen-receptor-alpha (ER) positive breast cancer (Cancer Res 2005, FASEB J 2007; Cancer Res 2009, Mol Endo 2012), which comprises ~75% of all cases but, paradoxically, an oncogenic role in ER-negative models such as the widely used MBA-MD-453 breast cancer cell line (EMBO J 2013; ERC 2012, Oncotarget 2015), which Prof Rob Sutherland and I characterized as a model of androgen stimulation (Eur J Cancer 1994). I was the first to measure ER and AR in breast tumours, show that the AR is a determinant of response to certain hormonal therapies and an independent predictor of disease outcome; (JCO 1995; Cancer Res 2005 & 2009) and that AR can antagonize ER action by binding to estrogen response elements in ER target genes (Cancer Res 2009). Most recently, my research has demonstrated functional cross-talk between sex hormone receptors in breast cancer, whereby ER is reprogrammed to elicit a good disease outcome (Nature 2015). This, coupled with the development of a unique ex vivo preclinical model to assess the efficacy of new drugs and identify biomarkers of treatment response in breast and prostate cancer (Cell Cycle 2012; Clin Canc Res 2012; Cancer Discov 2012; Nature 2015), has led to new strategies for targeting the AR (Nat Commun 2014). These papers continue to be highly cited with almost 10,000 total citations.

Publication of outstanding research in high ranking, peer reviewed journals. I have an excellent publication record with 200 peer-reviewed papers on the mechanism of sex steroid hormone action and the role their receptors play in the development and progression of breast and prostate cancers, with a particular emphasis on understanding de novo and acquired resistance to endocrine therapies in prostate cancer. In the last 12 months I have published several particularly high impact publications (Nature 2015; NAR, 2015; Nature Genetics, 2015; J Natl Cancer Inst, 2015; Oncogene 2016, Science Advances 2016, Nature Reviews Cancer 2016). The 2015 Nature paper, which instigated a paradigm shift in thinking about how progesterone functions in breast cancer, was profiled in multiple journals and received extensive press coverage world-wide. It is ranked as a highly cited paper in Web of Science, representing the top 0.1% of papers in the field. The Nucleic Acids Res article was selected as a Breakthrough article by the Editors as it provided exceptional new insight and understanding into how AR splice variants can drive the growth of metastatic prostate cancer.

An example of how my research contributions on the AR have made a major impact on the health outcomes of individuals. My research on androgens in breast cancer has underpinned a clinical trial of testosterone with an aromatase inhibitor (AI) to treat AI induced joint pain in postmenopausal women with breast cancer (ClinicalTrials.gov Identifier: NCT01573442). Additionally, my research has shown that the synthetic progestin medroxyprogesterone acetate (MPA), which is widely used in menopausal hormone therapy and associated with increased breast cancer risk, can disrupt the protective effects of androgens in the breast. This research has contributed to a recent move to develop strategies to reduce the use of synthetic progestins in women with postmenopausal symptoms and the WHO listing MPA as an endocrine disruptor of androgen action and a carcinogen (WHO cited FASEB J, 2007). Most recently, I have established a collaboration with GTx Pharmaceuticals, Memphis TN to develop a novel selective AR modulator (SARM) as a new therapeutic in breast cancer, which has resulted in funding from Cancer Research UK to evaluate a SARM in ER-positive, hormone naïve breast cancer (Emerald Trial; WDT Co-PI).

  • Appointments

    Date Position Institution name
    2012 - 2013 Visiting Scientist Cancer Research UK Cambridge Research Institute
    2011 Co-Director Adelaide Prostate Cancer Research Centre
    2002 Director University of Adelaide
    2001 - 2002 Visiting Fellow Norris Comprehensive Cancer Center, University of Southern California
    1996 - 2001 Director Flinders University and Flinders Medical Centre
    1992 - 1998 National Health and Medical Research Council (NHMRC) Senior Research Fellow and Senior Lecturer Flinders University
    1989 - 1990 Visiting Fellow University of Texas Southwestern Medical Center at Dallas
    1983 - 1986 NHMRC Senior Research Officer Flinders University
  • Awards and Achievements

    Date Type Title Institution Name Country Amount
    2016 Award 2016 Senior Plenary Award Endocrine Society of Australia Australia
    2015 Award Executive Dean’s Awards 2015 The University of Adelaide Australia
    2008 Award Ron Ross Award 4th PacRim Breast and Prostate Cancer Meeting Canada
  • Education

    Date Institution name Country Title
    1984 Flinders University of South Australia Australia PhD
  • Postgraduate Training

    Date Title Institution Country
    1987 - 1989 NHMRC CJ Martin Fellow University of Texas Southwestern Medical Center at Dallas United States
  • Research Interests

Significant contribution to successful grant applications. My track record in competitive grant funding is excellent, with 7 NHMRC project grants (CIA on 6) and an NHMRC Enabling grant in the last 5 years. I am a Co-PI (B) on the first multinational US Department of Defense Prostate Cancer Research Program Transformative Grant (2014-2016) to better understand mechanisms of resistance to new generation AR targeting drugs and develop novel drugs that more effectively target all forms of the AR. Additionally, I was a co-CI on one of the first national collaborative grants awarded by the National Breast Cancer Foundation  Clarke C, PI) to comprehensively study nuclear receptor function in breast cancer and I am a senior Team Leader on a Revolutionary Team Award from the Movember Foundation and the Prostate Cancer Foundation of Australia, which was awarded in 2014 (Butler L, CI) to study androgens and metabolism in prostate cancer.

  • Current Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2019 Co-Supervisor Elucidating the Interplay Between Androgen Receptor Signalling and Lipid Metabolism in Prostate Cancer Doctor of Philosophy Doctorate Full Time Ms Meiwen Danielle Fang
    2017 Co-Supervisor Role of the GATA3 transcription factor on AR signalling In ER-positive breast cancer Doctor of Philosophy Doctorate Full Time Mrs Leila HosseinZadeh
    2017 Co-Supervisor Interactions between Androgen signalling and the lipid microenvironment in prostate cancer Doctor of Philosophy Doctorate Full Time Mr Raj Kumar Shrestha
    2017 Co-Supervisor Androgen receptor co-regulators mediating the actions of selective androgen receptor modulators and dihydrotestosteron in TNBC Doctor of Philosophy Doctorate Full Time Mrs Ebtihal Hashem Mustafa
    2017 Co-Supervisor Development of Microfluidic Technology for Genomic Studies of Circulation Tumor Cells Doctor of Philosophy Doctorate Full Time Mr Mohammadreza Alizadeh Ghodsi
    2016 Co-Supervisor Unraveling the regulatory network underlying Androgen Deprivation Therapy- induced cancer stem cell traits in prostate cancer Doctor of Philosophy Doctorate Full Time Miss Rayzel Candida Fernandes
  • Past Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2010 - 2016 Co-Supervisor The Role of Estrogen Receptor and the Androgen Receptor in Human Breast Cancer Doctor of Philosophy Doctorate Part Time Mrs Shalini Jindal
    2009 - 2009 Other Contributions to the Early Diagnosis and Modern Management of Breast Cancer Doctor of Medicine Higher Doctorate Full Time Prof Gelareh Farshid
    2009 - 2013 Co-Supervisor Investigation into the Expression and Localisation of C-Kit and the Regulation of Kit Ligand Gene Expression in the Adult Human Ovary Doctor of Philosophy Doctorate Full Time Dr Astrud Tuck
    2008 - 2012 Co-Supervisor The Molecular Actions of Medroxyprogesterone Acetate on Androgen Receptor Signalling and the Promotion of Breast Cancer Doctor of Philosophy Doctorate Full Time Miss Aleksandra Ochnik
    2008 - 2011 Co-Supervisor Characterisation of the Co-chaperone Small Glutamine-rich Tetratricopeptide Repeat containing Protein Alpha as a Regulator of Androgen Receptor Activity in Prostate Cancer Cells Doctor of Philosophy Doctorate Full Time Dr Andrew Trotta
    2008 - 2012 Co-Supervisor The Role of Small Glutamine-Rich Tetratricopeptide Repeat Containing Protein Alpha in Female Reproductive Tissues Doctor of Philosophy Doctorate Full Time Ms Miriam Simone Butler
    2007 - 2012 Co-Supervisor Mathematical Models of Cell Cycle Progression: Applications to Breast Cancer Cell Lines Doctor of Philosophy Doctorate Part Time Miss Kate Simms
    2007 - 2015 Co-Supervisor Combinatorial Targeting of the Androgen Receptor for Prostate Cancer Therapy Doctor of Philosophy Doctorate Full Time Miss Sarah Carter
    2006 - 2010 Co-Supervisor The Role of Epigenetic Modifications in Prostate Tumourigenesis Doctor of Philosophy Doctorate Full Time Ms Karen Huiqin Chiam
    2004 - 2008 Co-Supervisor Characterisation of a Dominant Negative Androgen Receptor in Prostate Cancer Cells Doctor of Philosophy Doctorate Part Time Dr Margaret Centenera
    2004 - 2008 Co-Supervisor Androgen Signalling in Normal and Malignant Breast Epithelial Cells Doctor of Philosophy Doctorate Part Time Ms Amelia Peters
    2004 - 2008 Co-Supervisor Androgens and Androgen Receptor Signalling in Men Doctor of Philosophy Doctorate Full Time Dr Eleanor Need
    2003 - 2007 Principal Supervisor Targeting the Androgen Receptor as a Therapeutic Strategy for Prostate Cancer Doctor of Philosophy Doctorate Full Time Miss Deborah Marrocco
    2002 - 2004 Co-Supervisor Versican: regulation, purification, and biological properties of a candidate prognostic indicator for breast cancer Doctor of Philosophy Doctorate Full Time Miss Supaporn Suwiwat
    2002 - 2004 Principal Supervisor ANDROGEN SIGNALLING IN HUMAN BREAST CANCER CELLS Doctor of Philosophy Doctorate Full Time Miss Nicole Moore
  • Position: Director - Dame Roma Mitchell Cancer Res Lab
  • Phone: 83137861
  • Email: wayne.tilley@adelaide.edu.au
  • Campus: North Terrace
  • Building: Adelaide Health and Medical Sciences, floor 8
  • Room: WS8060.01
  • Org Unit: Medical Specialties

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