Advances in Biosciences Seminar - Dr Luke Gaughan, University of Newcastle. Topic: Prostate cancer splicing and endocrine resistance
|Dates:||28 November 2023|
|Times:||13:00 - 14:00|
|What is it:||Seminar|
|Organiser:||Faculty of Biology, Medicine and Health|
|Who is it for:||University staff|
|Speaker:||Dr Luke Gaughan|
1. Mechanisms of Androgen Receptor (AR) Regulation in Prostate Cancer
2. Epigenetics and splicing control of AR synthesis
The main theme of my research over the last 5 years has been to examine key molecular processes that govern and facilitate AR signalling in advanced prostate cancer with the ultimate objective to identify new targets for therapy. By developing new models of hormone
therapy-resistance that includes engineered cell lines (O’Neill et al., 2015; Jones et al., 2015; Jones et al., 2017) and patient biopsy material as explants, our toolkit for prostate cancer research has evolved to enable more robust, clinically-relevant interrogation of AR function. This has resulted in productive and long-standing industrial collaborations with AstraZeneca, and more recently with CellCentric and J&J, to facilitate Newcastle-based mechanism of action and efficacy studies of several clinical candidate epigenetic and hormonal therapeutics.
In the last 5 years, the group has identified and comprehensively validated a number of key AR coregulators in PC development, such as the histone demethylase enzyme KDM4B, which entered a collaborative CR UK-funded drug development campaign in collaboration with the Institute of Cancer Research, Sutton. In addition, our work has identified key processes that govern generation and activity of alternatively spliced forms of the AR, including Aurora kinase A and FOXA1. Furthermore, we have provided insight into the altered functionality of AR mutants in advanced disease that has highlighted new treatment targets and biomarkers for patients resistant to the hormonal therapies bicalutamide and enzalutamide.
Our more recent work has focused on the use of genome editing techniques to create genetically altered cell lines (e.g. CWR22Rv1-AR-EK; Kounatidou et al., (2019) Nucleic Acids Research) and as a platform to enable locus specific fluorescence and protein-protein interaction studies of all AR isoforms.
Dr Luke Gaughan
Role: Reader in Molecular Oncology
Organisation: University of Newcastle
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building