Biomedicine Seminar

Abstract
Prostate cancer is a multi-focal high-incidence cancer driven by androgen receptor activity.  It is characterized by early changes in metabolic dependency towards increased rates of lipid turnover and the use of cholesterol to support testosterone biosynthesis.  Genomically copy number instability and chromosomal fusions are characteristic of localized prostate cancer.  Somatic point mutations become more abundant as the disease metastasizes and this occurs in around 20-30% of diagnosed cases often over a period of 5-10 years post-diagnosis.  Immune surveillance of cancer cells is restricted as localized disease evolves. A variety of transcript and copy-number profiles have been proposed to prognosticate prostate cancer but none have been adopted routinely in clinical pathways.  From a biological perspective it is ever more important to understand how these molecular features emerge and how best to exploit them as therapeutic vulnerabilities and biomarkers.  This requires a detailed understanding of the cellular and microenvironmental context in which these changes occur. This seminar will exemplify some of this through past and current projects and in particular:

• Defining androgen receptor gene regulatory networks in prostate cancer.
• Targeting the unfolded protein response to change treatment response.
• Identifying features of radiotherapy-resistant prostate cancer.
• Impacts of OGlcNAc transferase on metabolic and transcriptional capacity.
• Interpreting these biologies in a spatial, multi-cell type context.