SciLifeLab Fellows seminar series: Metabolism and stress response signalling in prostate cancer
Speaker: Ian Mills, Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, UK
Prostate cancer is high incidence male cancer which progresses in a subset of diagnosed cases with a progression time of years. Lethal end-stage disease is characterised by somatic mutations in many of the same drivers that contribute to the progression of other types. Early stage/localised disease is predominantly characterised by changes in the activity of metabolic pathways and epigenetic reprogramming of the genome. The androgen receptor is a key transcription factor both in normal prostate development in the progression of prostate cancer and can be viewed as both an interpreter and driver of these early changes. This talk will describe how genome-level site maps for transcription factor recruitment and chromatin modifications have, when coupled to transcriptomic analysis, enabled the identification of prostate cancer biomarkers and therapeutic targets. Many of these targets are enzymes required for anabolic metabolism, RNA processing and protein folding. Targeting these enzymes by repurposing clinically approved drugs as well as with new agents has profound impacts on the stability and activity of p53 and c-Myc and the activation of pro-inflammatory and innate immune signalling. Characterising their biological impact will therefore require new pre-clinical models able to better capture changes in the microenvironment in response to these interventions. The talk will conclude with a forward perspective on these challenges.
Dr. Ian Mills undertook a PhD in Liverpool and a postdoc at the MRC-LMB in Cambridge studying aspects of endocytosis. His PhD involved the characterisation of lipid-binding endosomal tethers required to prime SNARE-mediated endosome fusion. His postdoc resulted in the characterisation of helical insertion by Epsins and curvature sensoring by BAR domain proteins as important mechanistic contributors to the formation of clathrin-coated vesicles. Dr. Mills then went on to work with Prof. David Neal, a surgical oncologist, to establish the first translational prostate cancer research programme in Cambridge. This led to the genome-wide characterisation of androgen receptor binding sites and target genes in prostate cancer and the discovery of novel multi-transcription factor complexes as regulators of gene expression. Based on these genome-wide maps and transcriptional networks he went on to study the contribution of metabolic and stress response genes as mediators of cancer cell survival and prostate cancer progression. This formed the focus of his group at the Centre for Molecular Medicine Norway (NCMM), a Nordic EMBL Partner. Most recently he has established a research group in Belfast within a Prostate Cancer UK/Movember-funded Centre continuing to study these pathways with a translational focus on modifying the microenviromental/immune response to therapeutic stress.
Date: Sept 11
Venue: Gamma 2, lunch room, SciLifeLab Solna
Host: Claudia Kutter
This seminar is part of a seminar series hosted by SciLifeLab Fellows