Understanding how EDAR-signalling modulates susceptibility to skin and colorectal cancer

This work will provide vital information to help stratify patients for EDAR-based therapy by determining the patient populations that are susceptible to oncogenic side-effects of these agents. It will also provide invaluable insight into the potential underlying mechanisms of cancer development in patient populations with high incidence of EDAR variants and thus reveal novel, future therapeutic targets.
EDAR is a cell-surface receptor that has pivotal roles during development. As well as being required developmentally, these pathways are frequently mutated in cancers, as alterations in these pathways enables cells to acquire many of the biological characteristics necessary to become cancerous. However, despite a clear link between the downstream pathways of EDAR signalling and cancer development, the specific role of EDAR signalling in cancer is poorly understood.
Our recent work has shown that over-activation of this pathway can drive breast and skin cancer development. These new findings; that EDAR-signalling is potentially cancer causing, are extremely important for two reasons; 1) several therapies are in development that stimulate EDAR signalling (e.g. for congenital deficiency in EDAR signalling), 2) East Asian and Native American groups have a high incidence of EDAR variants that cause over-activation of the pathway, which is potentially cancer-causing. Therefore there is a pressing need to 1) develop an effective way to model differential EDAR-signalling status to enable understanding of tumourigenesis in these discrete patient populations and 2) investigate the impact of EDAR signalling on tumour incidence and development in patients. These are the aims of this studentship.
Execution of this project involves collaboration with Shanghai Jiao Tong University School of Medicine (SJTUSM) and will employ a wide spectrum of research methods spanning in vitro molecular biology techniques to in vivo tumour modelling. This will provide the successful candidate with the breadth of knowledge and skills necessary for a successful future career in cancer research.