I am a clinician scientist, trained in renal and acute general medicine. After initially working on the physiology of renal oxygenation and its implications for renal injury in shock, I joined the Weatherall Institute of Molecular Medicine in 1989 and retrained in molecular and cell biology, changing fields to start a laboratory working on cellular oxygen-sensing pathways.
Working originally on the regulation of the erythropoietin gene by blood oxygen, the laboratory unexpectedly discovered that this process is part of a widely operative system of oxygen sensing that is present in all animal cells and regulates many other processes, including energy metabolism, angiogenesis, cell survival and cell differentiation. The laboratory went on to elucidate the nature of the oxygen-sensing process as an unprecedented type of cell signalling based on the post-translational hydroxylation of specific residues in the key transcription factor hypoxia inducible factor (HIF). These hydoxylations are catalysed by a series of Fe(II) and 2-oxoglutarate dependent dioxygenases whose absolute requirement for molecular oxygen as co-substrate confers oxygen sensitivity.
I am Member of the Ludwig Institute in Oxford where my laboratory works on the consequences of activation of these very extensive pathways in cancer, and on the physiological and biochemical characterization of other 2-oxoglutarate dependent dioxygenases and related enzymes that might play a role in signalling hypoxia or metabolic stresses in cancer and other diseases.
I served as Nuffield Professor and Head of the Nuffield Department of Clinical Medicine from 2004-2016. In May 2016 I took up a new position as Director of Clinical Research at the Francis Crick Institute, London retaining a half-time position in Oxford as Director of the Target Discovery Institute where I run my Ludwig laboratory. I was elected to the Fellowship of the Academy of Medical Sciences and to the Fellowship of the Royal Society in 2002, to EMBO in 2006 and as Foreign Honorary Member of the American Academy of Arts and Sciences in 2007.
Undergraduate medical training: Gonville and Cauis College, Cambridge and St. Bartholomew’s Hospital, London
Postgraduate: Training positions in Nephrology and General Medicine, London and Oxford Hospitals
Medical Research Council Training Fellowship, Oxford
Wellcome Trust Senior Fellowship in Clinical Science, Oxford
Louis-Jeantet Prize for Medicine, 2009
Canada Gairdner International Award, 2010
Robert J. and Claire Pasarow Foundation Award in Cardiovascular Research, 2011
Baly Medal, the Royal College of Physicians, 2011
Scientific Grand Prix of the Foundation Lefoulon-Delalande, Institute of France, 2012
Jakob-Herz-Preis, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany, 2013
KBE for services to Clinical Medicine, New Year’s Honours, 2014
Wiley Prize for Biomedical Science, 2014