Cell proliferation with excessive vascularisation: early stage cancer in a hypoxic state.

Peter Ratcliffe : Hypoxia Biology Laboratory

We are studying the ways cells sense and respond to low oxygen levels, and the role that these responses play in diseases including cancer.

Every single cell in the body needs oxygen to function, and without it they will die. If oxygen levels become too low (known as hypoxia), cells will switch on a variety of pathways and processes in order to survive.

One of the most important molecules in the hypoxia response is called HIF (hypoxia inducible factor). When a cell becomes hypoxic, HIF switches on many important genes that trigger a cascade of events that help it stay alive.

We are investigating how HIF is activated and deactivated, and how it works to switch on genes in response to low oxygen levels and other forms of stress. In particular, we are studying mechanisms by which oxygen levels in cells are sensed in order to control HIF and other pathways. These processes can be targeted by medicines that switch on defenses against hypoxia and we are working to understand how best to use them in disease.

Our findings are revealing more about hypoxia and the role it plays in a variety of health conditions, including heart disease, metabolic diseases and cancer. We are particularly interested in looking at the role of HIF and hypoxia in kidney cancer, a disease where HIF is constantly active even when oxygen levels are normal, which could point towards potential new cancer treatments.