My projects focus upon trying to identify novel synthetically lethal targets within cancer cells. Synthetic lethality is the concept that the loss or disruption of two particular genes at the same time is lethal for a cell, whereas the loss of either one alone does not impact cell viability. This is something that can potentially be exploited in cancer therapies as multiple genes are often already altered in cancer cells. Indeed, there are examples of this approach been used successfully in the clinic, with the best-known example the use of PARP inhibitors in cancers lacking BRCA. We are currently undertaking multiple customized CRISPR-Cas9 screens with the aim of identifying new synthetically lethal gene targets.
Ubiquitin-specific protease 12 interacting partners Uaf-1 and WDR20 are potential therapeutic targets in prostate cancer.
Deubiquitinating enzyme Usp12 is a novel co-activator of the androgen receptor.
The Journal of biological chemistry 2013;288;45;32641-50
Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1.
EMBO molecular medicine 2018;10;4
Deubiquitinating enzyme Usp12 regulates the interaction between the androgen receptor and the Akt pathway.