Centre for Urological Research, Monash University Prostate Cancer BioResource Consortium

Monash Institute of Reproductive development...

Chief Investigators

Professor Gail Risbridger, Centre Head 1
Associate Professor Mark Frydenberg, Clinical Director2
Dr Caroline Dowling, Urologist2
Mr Laurence Harewood, Urologist3
Mr Jeremy Goad, Urologist4
Professor John Mills, Director5
Associate Professor John Pedersen, Pathologist5
Dr Tim Nottle, Pathologist5
Dr. Renea Taylor (nee Jarred), Senior Research Fellow1
Dr. Stephen McPherson, Research Fellow1
Dr. Elspeth Gold, Research Fellow1
Dr. Brindi Niranjan, Research Fellow1
Dr. Preetika Balanathan, Research Fellow1
Dr. Stuart Ellem, Research Fellow1
Dr Kara Britt, Research Fellow
Mr Brian Golat, APCC BioResource Node Coordinator

Affiliations

1. Monash Institute of Medical Research, Monash University
2. Department of Urology, Monash Medical Centre
3. Epworth Hospital
4. St Vincent’s and Mercy Private Hospital
5. TissuPath histopathology laboratory

Research Activity

The Centre for Urological Research is a group of scientists and clinical fellows working together to identify novel diagnostic and therapeutic agents for prostate cancer. The Centre is located at Monash Medical Centre, adjacent to the hospital and Department of Urology, which facilitates collaboration between Urology staff and research scientists.

The group has several main research areas including:

1. Understanding the role of growth factors in regulating prostate development and disease, specifically the inhibin and activin family of ligands.
2. Exploring the impact of early events on late life disease in relation to prostate disease; in particular the role of endocrine disruptor chemicals and possible long term effects on the prostate.
3. Investigation of the hormonal regulation of prostate diseases including prostate enlargement (BPH) and prostate cancer.
4. Development of prostate cancer diagnostic or prognostic tools to be applied in the clinic.
5. Identifying adult prostatic stem cells as potential therapeutic targets for prostate cancer therapeutics.

Research Areas of Expertise:

Prostate development, prostate cancer, estrogen action, steroid receptors, growth factors (including activin & inhibin), aromatase action, potential diagnostic or prognostic agents for prostate cancer.

Laboratory areas of expertise - animal models, imaging and stereology, histology & pathology, tissue recombination and cell culture, laser capture microdissection, endocrine assays, pre-clinical drug testing, clinical studies.

Major Prostate Cancer Related Grants (last 5 years)

Stem cells in prostate. 2003 – 2005, $375,000 US Prostate Cancer Research Idea Award, USA Army Medical Research & Materiel Command (DOD); Risbridger GP, Trounson A.

Predictive value of inhibin as a marker for prostate cancer. 2004-2005, $150,534, Prostate Diagnostics Pty Ltd; Risbridger GP.

Melbourne Male Network. 2004-2005, 900,000 Euros, Schering AG; Risbridger GP, de Kretser D, Simpson ER, McLachlan R, O’Bryan M.

Australian Prostate Cancer Collaboration (APCC) BioResource. 2004-2009, $2.1million. NHMRC Enabling Grant, Clements JA, Sutherland RL, Risbridger GP, Tilley WD.

Development of a blood test for life threatening prostate cancer. 2005-2006, $144,650 NH&MRC Development Grant, Risbridger GP.

Control of Reproductive Processes. 2005-2007, $4,635,222 NH&MRC Program Grant, de Kretser D, Risbridger GP, Hedger M, Hearn M, Jenkin G, Loveland KL, O’Bryan M, Wallace E.

Is hormonal induction of prostate carcinogenesis due to declining androgens in late life and/or increased estrogen in early life? 2006-2008, $US219,334 USA Army Medical Research & Materiel Command (DOD) New Investigator Award, McPherson S, Risbridger GP

Early origins of prostate cancer. 2006-2008, $203,000 Cancer Council Victoria Project Grant, Risbridger GP, McPherson S

Endocrine disruption and human prostate cancer 2007 $96,644US USA Army Medical Research & Material Command (DOD) Exploration Hypothesis Development Award, Risbridger GP

New action of inhibin alpha subunit in advanced prostate cancer 2007-2008 $113,614US USA Army Medical Research & Material Command (DOD) New investigator Award Balanathan P, Risbridger GP

Using human stem cells to study the role of the stroma in the initiation of prostate cancer 2008-2010 $464,646US USA Army Medical Research & Material Command (DOD) Idea Development Award, Taylor R, Risbridger GP

Melbourne Male Network 2006-2008 $2,386,858 Schering AG; Risbridger GP, de Kretser D, Simpson ER, McLachlan R, O’Bryan M.

MicroRNAs in Prostate Cancer – novel biomarkers and potential therapeutic targets 2008-2010 $648,000 Prostate Cancer Foundation Australia, Nelson C, Risbridger GP, Tilley W, Clements J, Nicol D

Linking estrogen, prostatitis and prostate cancer 2008-2010 $144,923 USA Army Medical Research & Material Command (DOD) Prostate Cancer Training Award, Ellem S, Risbridger GP

Molecular profiling and plasticity of prostate cancer stem cells with disease progression 2008-2011 $300,000 Prostate Cancer Foundation Australia, Taylor R

Liquid chromatography tandem mass spectrum steroid analysis Facility 2008 $356,000 Australian Research Council – Linkage Infrastructure, Equipment and Facilities Scheme, Handlesman D, Norman R, Risbridger GP, Liu

Selected Prostate Cancer Related Publications (last 5 years)

Jarred RA, McPherson SJ, Jones MEE, Simpson ER, Risbridger GP. Anti-androgenic action by red clover-derived dietary isoflavones reduces non-malignant prostate enlargement in aromatase knockout (ArKO) mice. The Prostate, 56 (1): 54-64, 2003.

Mellor SL, Ball EMA, O’Connor AE, Ethier J-F, Cranfield M, Schmitt JF, Phillips DJ, Groome NP, Risbridger GP. Activin βc subunit heterodimers provide a new mechanism for regulating activin levels in the prostate. Endocrinology, 144(10):4410-9, 2003.

Risbridger GP, Shibata A, Ferguson KL, Stamey TA, McNeal JE, Peehl DM. Elevated expression of inhibin α in prostate cancer. Journal of Urology. 171, 192-196, 2004.

Balanathan P, Ball EMA, Wang H, Harris SE, Shelling AN, Risbridger GP. pigenetic regulation of Inhibin alpha subunit gene in prostate cancer cell lines. Journal of Molecular Endocrinology. 32 (1): 55-67, 2004.

Ellem S, Schmitt J, Pedersen J, Frydenberg M, Risbridger G. Local aromatase expression in human prostate is altered in malignancy. Journal of Clinical Endocrinology and Metabolism. 89(5):2434-41, 2004.

Ilic D, Risbridger G, Green S. Searching the internet for information on prostate cancer screening: an assessment of quality. Urology (64) 1: 112-116, 2004.

Risbridger G, Ball E, Wang H, Mellor S, Peehl D. Re-evaluation of inhibin α subunit as a tumour suppressor in prostate cancer. Mol Cell Endocrinol, 225, 73–76, 2004.

Cunha GR, Ricke W, Thomson A, Marker PC, Risbridger GP, Hayward S, Wang YZ, Donjacour AA, Kurita T. Hormonal, cellular and molecular regulation of normal and neoplastic prostatic development. Journal of Steroid Biochemistry & Molecular Biology 92:221:236, 2004.

Ball, EMA, Mellor SL, Risbridger GP. Cancer progression: is inhibin α from Venus or Mars? Cytokine and Growth Factor Reviews. 15, 5, 291-296, 2004.

Almahbobi G, Hedwards, S, Fricout G, Jeulin D, Bertram JF, Risbridger GP. Computer-based detection of early changes to branching morphogenesis reveals multiple mechanisms of prostate enlargement. Journal of Pathology 206(1):52-61, 2005.

Risbridger GP, Almahbobi GA, Taylor RA. Early prostate development and its associate with late life prostate disease. Cell and Tissue Research Oct; 322(1):173-81, 2005

Ilic D, Risbridger G, Green S. The informed male: what do men want to know about prostate cancer screening? International Journal on Mens Health and Gender 2,4:414-420, 2005

Taylor RA, Cowin , Couse JF, Korach KS, Risbridger GP 17b-estradiol induces apoptosis in the developing rodent prostate independently of ERα or ERβ. Endocrinology 147(1): 191-200, 2006

Taylor RA, Cowin, PA., Cunha GR, Pera M, Trounson AO, Pedersen J, Risbridger GP. Formation of human prostate tissue from embryonic stem cells. Nature Methods 3 (3):179-181, 2006

Bianco JJ, McPherson SJ, Wang H, Prins GS, Risbridger GP, Transient neonatal estrogen exposure to estrogen deficient mice (Aromatase knockout) reduces prostate weight and induces inflammation in late life. Am J Pathol. Jun;168(6):1869-78. 2006

McPherson, SJ, Ellem SJ, Simpson, ER, Patchev, V, Fritzemeier, K-H, Risbridger, GP (2007) Essential role for estrogen receptor β in stromal-epithelial regulation of prostatic hyperplasia. Endocrinology. 148(2):566-74

Ricke WA, McPherson SJ, Bianco JJ, Cunha GR, Wang Y, Risbridger GP. 2008. Prostatic hormonal carcinogeneis is mediated by in situ estrogen production and estrogen receptor alpha-signaling. FASEB Journal, 22(5):1512-1520

Ellem SJ & Risbridger GP. (2007) Treating Prostate Cancer; A rationale for targeting local estrogens. Nature Review Cancer, (8): 621-627

Risbridger GP, Ellem SJ, McPherson SJ (2007). Estrogen action on the prostate gland: A critical mix of endocrine and paracrine signalling. Journal of Molecular Endocrinology. J Mol Endo, 39(3): 183-8

Risbridger GP, Taylor RA (2008). Regulation of prostatic stem cells by stromal niche in health and disease. Endocrinology. 149(9):4303-4306

Gold E, Jetly N, O’Bryan MK, Meachem S, Srinivasan D, Behuria S, Sanchez-Partida G, Woodruff T, Hedwards S, Wang H, McDougall H, Casey V, Niranjan B, Patella S, Risbridger GP. (2008) Activin C antagonizes activin A in vitro and overexpression leads to pathologies in vivo. Am J Path (In Press)

Taylor RA, Risbridger GP (2008). The path towards identifying prostatic stem cells. Differentiation. 76(6):671-681

McPherson SJ, Ellem SJ, Risbridger GP (2008). Estrogen regulated development and differentiation of the prostate. Differentiation. 76(6):660-670

Hung T-T, Wang H, Kingsley E, Risbridger GP, Russell PJ (2008). Molecular profiling of bladder cancer: Involvement of the TGF-β pathway in bladder cancer progression. Cancer Letters. 265(1):27-38

Taylor RA, Risbridger GP (2008). Prostatic tumour stroma: a key player in cancer progression. Invited Review for Current Cancer Drug Targets – Special edition on Targeting Tumour Stroma; series on Hot Topics in Cancer 8(6): 490-7

Cowin, P, Foster P, Pedersen J, Hedwards S, McPherson S, Risbridger G (2008). Early onset endocrine disruptor-induced prostatitis in the rat. Environmental Health Perspectives, 116(7):923-9

Ilic D, Egberts K, McKenzie J, Risbridger G, Green S. 2008. Informing men about prostate cancer screening; a randomized controlled trial of patient education materials. Journal of General Internal Medicine, 23(4):466-71

Book Chapters

Risbridger GP, Frydenberg, M. 2004 Endocrinology of Prostate Cancer. In Endocrinology. (Ed. Leslie J. De Groot) 4th edition. W.B. Sanders, Philadelphia, PA. In press

Risbridger GP, Taylor R. 2004 The physiology of the male sex accessory tissues. In Physiology of Reproduction (Ed. J. D. Neill) 3rd edition. Elsevier, San Diego, CA. In press

Risbridger, Gail P. Activins. 2003 In Encyclopaedia of Hormones. Growth Factors and Cytokines. Elsevier Press, Academic Press, San Diego

Simpson ER, McPherson S, Jones M, Robertson K, Boon WC, Risbridger G. (2004) Role of estrogens in the male reproductive tract In: New molecular mechanisms of estrogen action and their impact on future perspectives in estrogen therapy. Ernst Schering Research Foundation Workshop 46. (Eds. KS Korach, A. Hillisch, FH Fritzemeier). Springer-Verlag Berlin. p89-125.

Risbridger, GP, Frydenberg, M. 2006 Endocrinology of Prostate Cancer, In Endocrinology. Editor: Leslie J. De Groot. 5th edition Elsevier, W.B. Sanders, Philadelphia, PA. p3325-3337

Ellem SJ, Risbridger, GP. Aromatase and prostate cancer. Minerva Endocrinologica 31 (1) 1-12, 2006

Risbridger, GP, Taylor R. 2006 The physiology of the male sex accessory tissues. In Physiology of Reproduction, Editor J. D. Neill. 3rd edition. Elsevier, San Diego, CA. P1149-1172

Risbridger, Gail P. Activins. 2006 Encyclopaedia of Hormones. Growth Factors and Cytokines. Editors: Elsevier Press, Academic Press, San Diego

Risbridger, GP. and Butler, C, 2006 Activins and Leydig cell development, differentiation and disease (Chapter 22 ) from Contemporary Endorinology. In The Leydig Cell in Health and Disease, p323-331, Humana Press.

Risbridger, GP, Butler C (2007). Activins and inhibin in cancer progression in Transforming Growth Factor-Beta in Cancer Therapy, Volume 1: Basic and Clinical Biology. Ed: Sonia B. Jakowlew, Humana Press. (26):411-424

Cowin PA, Foster P, Risbridger, GP (2007). Endocrine Disruption in the Male, Endocrine disrupting Chemicals: From Basic Research to Clinical Practice, (3): 33-62, Humana Press

Ellem SJ & McPherson SJ, Patchev V, Fritzmeier KH and Risbridger, GP, (2007). The Role of ER Alpha and Beta In the Prostate. Insights From Genetic Models and Isoform-Selective Ligands, Tissue-Specific Estrogen Action: Novel Mechanisms, Movel Ligands, Novel Therapies? Ernst Schering Foundation, Pringer-Verlag, p. 131-147

International Patents

2005901642 Australia, 2005. Monash University. A method for diagnosis & treatment & agents useful for same.

PCT/AU 2005/000283 USA, 2005. Monash University. A method of screening and agents useful for same.

PCT/AU 2005/000542 USA, 2004. Monash University. A method of diagnosis.

WO2004/086048 Multiple Countries, 2004. Monash University. Diagnosis of advanced cancer.

WO2004/053487 Multiple Countries, 2003. Monash University. Methods of diagnosis, treatment & useful agents for conditions of characterised by the modulation in the level of activin beta C.

10/318,283 USA, 2001. Monash University. Methods & compositions for detecting an activin dimer.

WO98/47526 Multiple Countries, 1998. Monash University. Inhibin modulation of cell growth.

WO98/54358 Multiple Countries, 1998. Monash University. A method of diagnosing abnormal cell growth.