Approximately 50 per cent of Australian men experience some type of prostate problem during their lifetime, benign or malignant.
Of these, prostate cancer is one of the most common forms of cancer in men, affecting one in six men throughout their lifetime. The Risbridger laboratory works closely with clinicians to develop a better understanding of the mechanisms that drive prostate cancer and benign disease, with the ultimate goal of providing better diagnosis and treatment for patients. Our research utilises state-of-the-art techniques (such as xenografts, bioengineered in vitro modelling, transgenic models) that allow us to examine the mechanisms that contribute to disease development and progression.
Current research areas and/or themes within the group include:
- Defining the features of familial and high-risk prostate cancer.
- Survival signalling in prostate cancer.
- Patient-derived xenograft models of prostate cancer.
- Mechanisms and regulation of the tumour microenvironment.
- 3D in vitro modelling of the human prostate cancer microenvironment.
- Oestrogen signalling and inflammation.
Alsop K, Thorne H, Sandhu S, Hamilton A, Mintoff C, Christie E, Spruyt O, Williams S, McNally O, Mileshkin L, Ananda S, Hallo J, Loi S, Scott C, Savas P, Devereux L, Leditschke J, O’Brien P, Gunawardena S, Hampson C, Strachan K, Diana Jaravaza R, Francis V, Young G, Ranson D, Samaranayake R, Madadin M, Stevens D, Boyle S, Fedele C, Topp M, Ho G, Teo Z, Taylor R, Papargiris M, Lawrence M, Wang H, Risbridger G, et al. (2016). A community-based model of rapid autopsy in end-stage cancer patients. Nat Biotechnol. 34(10):1010-1014.
Risbridger GP, Taylor RA, Clouston D, Sliwinski A, Thorne H, Hunter S, Li J, Mitchell G, Murphy D, Frydenberg M, Pook D, Pedersen J, Toivanen R, Wang H, Papargiris M, Lawrence MG, Bolton DM (2015). Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis. Eur Urol. 67(3):496-503.
Takizawa I, Lawrence MG, Balanathan P, Rebello R, Pearson HB, Garg E, Pedersen J, Pouliot N, Nadon R, Watt MJ, Taylor RA, Humbert P, Topisirovic I, Larsson O, Risbridger GP, Furic L (2015). Estrogen receptor alpha drives proliferation in PTEN-deficient prostate carcinoma by stimulating survival signaling, MYC expression and altering glucose sensitivity. Oncotarget. 6(2):604-16.
Ellem SJ1, Taylor RA, Furic L, Larsson O, Frydenberg M, Pook D, Pedersen J, Cawsey B, Trotta A, Need E, Buchanan G, Risbridger GP (2014). A pro-tumorigenic loop at the human prostate tumor interface orchestrated by oestrogen, CXCL12 and mast cell recruitment. J Pathol. 234(1):86-98.
McGrath MJ, Binge LC, Sriratana A, Wang H, Robinson PA, Pook D, Fedele CG, Brown S, Dyson JM, Cottle DL, Cowling BS, Niranjan B, Risbridger GP, Mitchell CA (2013). Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer. Cancer Res. 73(16):5066-79.
Toivanen R, Frydenberg M, Murphy D, Pedersen J, Ryan A, Pook D, Berman DM, Australian Prostate Cancer BioResource, Taylor RA, Risbridger GP (2013). A preclinical xenograft model identifies castration-tolerant cancer-repopulating cells in localized prostate tumors. Sci Transl Med. 5(187):187ra71.
Lawrence MG, Taylor RA, Toivanen R, Pedersen J, Norden S, Pook DW, Frydenberg M; Australian Prostate Cancer BioResource, Papargiris MM, Niranjan B, Richards MG, Wang H, Collins AT, Maitland NJ, Risbridger GP (2013). A preclinical xenograft model of prostate cancer using human tumours. Nat Protoc. 8(5):836-48.
Prostate Cancer Research Group
PhD position available
The Prostate Cancer Research Group is a group of scientists and clinical fellows working together to study male urological biology and disease. This group is internationally recognised as pioneers and leaders in the development of patient-derived models of disease. We now have an opportunity for a PhD candidate to undertake an exciting new project in bladder cancer.
Bladder cancer effects over 2,500 Australians each year and is significantly more common in men than women. This project will explore the biological and genomic features of bladder cancer, using newly established patient-derived models. The outcomes of the work will have a major impact on future treatment and management of bladder cancer patients.
Primary Location: Monash University, Clayton, Victoria.
- This project will also require travel and interaction with clinicians at the Peter MacCallum Cancer Institute, Melbourne and perhaps other hospital sites around Melbourne.
Preference will be given to students eligible for the Australian Government Research Training Program (RTP) Stipend or a Monash Graduate Scholarship
- A scholarship equivalent to RTP rates ($27,353 p.a. full-time for 2018) is also available for outstanding applicants who are not eligible for these awards
Requirements & Application Instructions:
Candidates must have:
- A Science/Biomedical Degree with First Class Honours (or equivalent)
- Excellent oral and written communication skills
- Australian citizenship or permanent residency
- Experience with cell, tissue culture, and/or xenografting techniques will also be highly regarded
To apply, please ensure you include with your application:
- A detailed curriculum vitae including academic transcript(s)
- Names and contact details of 2 referees
- A brief outline (<1 page) detailing your interest in, and suitability for, this project
Please submit all applications and queries for more information to Prof Gail Risbridger ([email protected])
Honours Projects 2017
- New model for rapid preclinical testing of lethal prostate cancer
Description: Prostate cancer is the most commonly diagnosed cancer in Victoria. Unfortunately, important research is constrained by the paucity of experimental models for studying prostate cancer, which is more difficult to grow in the laboratory than many other types of cancer. Our laboratory has been successful in keeping rare patient samples of prostate cancer tissue alive as “patient-derived xenografts”. These samples represent an invaluable resource for testing novel therapeutics for prostate cancer.
The goal of this project is to maximise the utility of patient-derived xenografts by optimising a new technique known as ex vivo culture or explants. With this method, slices of viable pieces of tumour tissue can be treated with drugs of interest to identify the most promising compounds for further in vivo studies.
The project will involve a variety of techniques including dissections, use of a tissue slicer, tissue culture, immunohistochemistry, automated image analysis and quantitative PCR.
Contact: [email protected]
- Defining epigenome changes in the tumour microenvironment
Description: The tumour microenvironment has a functional role in the progression of prostate cancer. Furthermore, our laboratory has recently shown that cells within the tumour microenvironment, known as cancer-associated fibroblasts (CAFs), acquire consistent changes in DNA methylation. These epigenome marks are highly consistent between patients and represent possible new biomarkers for improving the accuracy of cancer diagnosis.
The goal of this project is to use 3D tissue culture models to study how reciprocal signalling between cancer cells and fibroblasts shapes the pattern of DNA methylation in each cell type. The results will identify the most important epigenome marks to validate as new biomarkers for prostate cancer.
The project will involve co-cultures of different cell types in custom-designed 3D scaffolds. The interactions between the cells will be examined using confocal microscopy and image analysis software. DNA methylation and gene expression changes will be examined using targeted bisulphite sequencing and quantitative PCR.
Contact: [email protected]