In 1989, Ratcliffe established a laboratory in
Oxford University's
Nuffield Department of Medicine to explore the regulation of
erythropoietin (EPO), a hormone released by the
kidneys and responsible for stimulating the production of
red blood cells. EPO was known to be produced by the kidneys in response to low oxygen levels, and Ratcliffe's work looked to understand the mechanisms of how the kidneys detected hypoxia (low oxygen levels in the blood) to trigger EPO production. From his studies, Ratcliffe discovered that the
mRNA from kidneys that were part of the EPO production pathway that were capable of detecting hypoxia was also present in several other organs, both human and animal, including the spleen, brain, and testes. His group found that cells from these organs could switch on EPO production when deprived of oxygen. Further, Ratcliffe was able to modify other cells using the identified mRNA to give these cells oxygen-sensing capabilities. This same pathway is also switched on in many cancer tumours, allowing them to create new blood vessels to sustain their growth. Much of the current understanding of hypoxia has emerged from the laboratory of Ratcliffe. The understanding of the molecular pathway of EPO production from hypoxia has led to the development of drugs that block VHL from binding with HIF to help treat patients with
anaemia and
kidney failure. == Personal life ==