Orphan GPR35 controls the quintessential sodium-potassium pump

GPR35 is a membrane receptor which is highly expressed in the intestine and immune system. A variant of the receptor increases risk for inflammatory diseases of the intestinal tract. We found that GPR35 uniquely forms a complex with the sodium/potassium pump (Na/K-ATPase) and promotes its pump and signalling function, which is further increased in the disease risk variant. This is important since Na/K-ATPase maintains intracellular electrolytes in all cells. GPR35 thereby plays a role in tumour promotion.

I will investigate how GPR35 interacts with Na/K-ATPase and promotes its function. I will also investigate how GPR35 affects the function of the immune system to understand how it predisposes for disease and how it affects the neo-vascularisation in tumours and its role in the tumour micro-environment. 

This project may reveal how a receptor regulates one of the most fundamental cellular processes, thereby underpinning its role as a disease risk-gene.