Peter J. Ratcliffe | |
|---|---|
.jpg) Ratcliffe in 2019 | |
| Born | Peter John Ratcliffe (1954-05-14)14 May 1954 (age 70) |
| Education | Gonville and Caius College, Cambridge St Bartholomew's Hospital Medical College |
| Awards | Fellow of the Royal Society Albert Lasker Award for Basic Medical Research Physiological Society Annual Review Prize Lecture Louis-Jeantet Prize for Medicine Knight Bachelor Fellow of the Academy of Medical Sciences EMBO Membership Baly Medal Grand Prix scientifique de la Fondation Lefoulon-Delalande Robert J. and Claire Pasarow Foundation Medical Research Award Nobel Prize in Physiology or Medicine |
| Scientific career | |
| Institutions | Francis Crick Institute Nuffield Department of Population Health,University of Oxford |
| Website | Official website |
Sir Peter John Ratcliffe,FRS,FMedSci (born 14 May 1954) is a Britishphysician-scientist who is trained as anephrologist.[1][2][3] He was a practising clinician at theJohn Radcliffe Hospital, Oxford andNuffield Professor of Clinical Medicine and head of the Nuffield Department of Clinical Medicine at theUniversity of Oxford from 2004 to 2016. He has been a Fellow ofMagdalen College, Oxford since 2004. In 2016 he became Clinical Research Director at theFrancis Crick Institute,[4] retaining a position at Oxford as a member of the Ludwig Institute of Cancer Research and director of the Target Discovery Institute, University of Oxford.[5]
Ratcliffe is best known for his work on cellular reactions tohypoxia, for which he shared the 2019Nobel Prize in Physiology or Medicine withWilliam Kaelin Jr. andGregg L. Semenza.[6][7]
Ratcliffe was born in Lancashire[8] on 14 May 1954, to William Ratcliffe, a lawyer, and Alice Margaret Ratcliffe, a telephonist.[9][10] He attendedLancaster Royal Grammar School from 1965 to 1972.[11]
He won an open scholarship toGonville and Caius College, Cambridge in 1972 to study Medicine at theUniversity of Cambridge[12] and then completed hisMB BChir medical degree withdistinction atSt Bartholomew's Hospital Medical College in 1978.[13]
Ratcliffe then trained in renal medicine at Oxford University, focusing on renal oxygenation.[14] He earned a higherMD degree from University of Cambridge in 1987.[15]
In 1990, Ratcliffe received aWellcome Trust Senior Fellowship to study cellular responses tohypoxia from low oxygen levels in the blood.[13][16]From 1992 to 2004 he was senior research fellow in clinical medicine atJesus College, Oxford.[17] In 2002, Ratcliffe was accepted into theAcademy of Medical Sciences and was appointed the following year the Nuffield Professor and head of the Nuffield Department of Clinical Medicine at Oxford.[18]
In 1989, Ratcliffe established a laboratory inOxford University'sNuffield Department of Medicine to explore the regulation oferythropoietin (EPO), a hormone released by thekidneys and responsible for stimulating the production ofred 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 themRNA 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.[19] His group found that cells from these organs could switch on EPO production when deprived of oxygen.[18] Further, Ratcliffe was able to modify other cells using the identified mRNA to give these cells oxygen-sensing capabilities.[19]
Building on these discoveries, the Ratcliffe group, along with joint studies withWilliam Kaelin andGregg Semenza, helped to uncover a detailed molecular chain of events that cells use to sense oxygen. A specific step identified was the binding of proteins expressed by theVon Hippel–Lindau tumor suppressor gene (VHL) tohypoxia-inducible factors (HIF), atranscription factor which trans-activates the EPO gene. Ratcliffe found that the VHL protein can bind a hydroxylated residues of HIF when oxygen is present at acceptable levels; the VHL protein then ubiquitylates the HIF protein which ultimately leads to the HIF protein's destruction. When oxygen levels fall, oxygen-requiringHIF hydroxylase enzymes, PHD1, 2 and 3 no longer act and VHL does not bind HIF, allowing HIF to remain and activate the EPO gene. This is a process that takes minutes to complete allowing the body to react quickly to hypoxia.[2]
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.[14] 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 withanaemia andkidney failure.[2]
Ratcliffe married Fiona Mary MacDougall in 1983.[10]
Ratcliffe has received a number of awards, accolades, and honours for his seminal work on hypoxia.
He wasknighted in the 2014 New Year Honours for services to clinical medicine.[27]
Further support for an oxygen-sensing mechanism was provided by the discovery of erythropoietin (EPO), a glycoprotein hormone that stimulateserythrocyte production [...] During the same time period in which Semenza was developing EPO-transgenic mice, Peter Ratcliffe, a physician and kidney specialist, was establishing a laboratory in Oxford University's Nuffield Department of Medicine to study the regulation of EPO
including the Nobel Lecture on 7 December 2019Elucidation of Oxygen Sensing Systems in Human and Animal Cells
