Prostate cancer will affect approximately one in seven Australian men and results in more than 3000 deaths per annum in this country alone.
To improve outcomes for men with this disease, the Prostate Cancer Research Group at Flinders University undertakes basic research to characterise the mechanisms by which prostate tumours metastasise and become resistant to targeted therapies. We feed this new knowledge into translational research projects aimed at developing new drugs and biomarkers to improve the treatment and management of patients.
Our group collaborates widely with prostate cancer consumer advocates, other scientists, clinicians, computational biologists and engineers – in Australia and around the world – to ensure that our findings have maximal impact. Importantly, our “team science” approach means that we also undertake impactful research on other types of cancer, most notably breast cancer.
Major research programs in the Prostate Cancer Research Group include:
Aberrant androgen receptor (AR) signaling in prostate cancer: Our team has uncovered mechanisms by which aberrant forms of the AR (AR mutants, truncated AR variants) drive therapy resistance in drug-resistant forms of prostate cancer, including identification of new AR co-regulators using integrative genomic techniques (Chan et al, Nucleic Acids Research 2015; Hickey et al, Oncotarget 2015; Paltoglou et al, Cancer Research 2017; Luo et al, European Urology 2017; Lawrence et al, European Urology 2018).
Transcriptional and epigenetic regulation of prostate cancer cell plasticity: We have defined new mechanisms by which microRNAs (Selth et al, Oncogene 2016; Das et al, Cancer Research 2017; Pillman et al, EMBO J 2018; Fernandes et al, Cell Reports 2021), transcription factors (Tse et al, Oncogene 2017; Miao et al, Cancer Research 2017) and epigenetic enzymes (Davies et al, Nature Cell Biology 2021) control cancer cell plasticity and thereby influence prostate cancer metastasis and therapy resistance.
Pre-clinical drug and biomarker development in prostate cancer: We have investigated the development and pre-clinical evaluation of multiple new therapeutic strategies (Gillis et al, Oncotarget 2013; Ponnusamy et al, Cancer Research 2017; Watt et al, Science Translational Medicine 2019) and biomarkers (Selth et al, International Journal of Cancer 2012; Selth et al, British Journal of Cancer 2013; Selth et al, Endocrine-Related Cancer 2014; Selth et al, Oncogene 2016) for prostate cancer.
Functional genomics of steroid hormone receptors in breast cancer: We have demonstrated that both cell context and interplay between steroid hormone receptors has a major impact on breast cancer pathobiology (Need et al, Molecular Endocrinology 2012; Hu et al, Cancer Research 2016; Holding et al, Genome Biology 2019; Hickey et al, Nature Medicine 2021).
Androgens as regulators of prostate cancer metabolism: We are investigating how the AR signalling axis influences prostate cancer metabolism, with a particular interest in glucose and lipid metabolism (Nassar et al, eLife 2020; Gillis et al, eLife 2021; Centenera et al, Cancer Research 2021).
Current research projects in the Prostate Cancer Research Group include:
Aberrant androgen receptor (AR) signaling in prostate cancer: We continue to research how the activity of AR evolves during prostate cancer progression, with a particular emphasis on the genomic actions of aberrant forms of the AR (mutants, truncated variants) in lethal disease states. Funded by Cancer Australia, Cancer Council SA and The Hospital Research Foundation.
Transcriptional and epigenetic regulation of prostate cancer cell plasticity: We are investigating how AR-targeted therapies increase cancer cell plasticity, leading to neuroendocrine and other phenotypes (e.g. epithelial-mesenchymal transition).Funded by Cancer Council SA and The Hospital Research Foundation.
Targeting CDK9 in lethal prostate cancer: CDK9 is a kinase that enhances prostate cancer growth by enhancing transcription of oncogenes. In collaboration with Prof Shudong Wang (University of South Australia), we are investigating CDK9 inhibitors as novel therapeutics for prostate cancer and using them as tools to understand CDK9 activity. Funded by Cancer Australia and The Hospital Research Foundation.
Androgens as regulators of prostate cancer immunology: Immunotherapy only works in a very small subset of patients with lethal prostate cancer. We are investigating whether androgens can be harnessed to sensitise tumours to immunotherapy. Funded by Cancer Council NSW, Cancer Council SA, the Freemasons Foundation for Male Health and Wellbeing and a generous donation from Ralph and Pixie Ernst.
After completing my PhD in Adelaide in 2005, I undertook post-doctoral studies at Cancer Research UK’s London Research Institute, funded by a prestigious EMBO long-term postdoctoral fellowship. There, I developed expertise in cancer biology and a skill-set in advanced molecular biology, biochemistry and bioinformatics. Returning to Adelaide in 2009, I won multiple fellowships (including a Prostate Cancer Foundation Young Investigator Award) to establish a new research program in prostate cancer. My lab at Flinders University, based at the Flinders Centre for Innovation in Cancer, is focused on improving outcomes for cancer patients.
Our lab is always on the lookout for students and post-docs who are passionate about making a difference to cancer patients. We are particularly interested in those with diverse skills and knowledge, including in the fields of biochemistry and molecular biology, health and medical sciences, biotechnology and bioinformatics.
Most of our projects are primarily comprised of “wet lab” research, but students interested in undertaking “dry lab” (i.e. bioinformatics) research are also encouraged to get in touch. Please contact A/Prof Selth directly.
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