15/10/19

Congratulations to Sir Peter Ratcliffe

Winner of the Nobel Prize in Physiology or Medicine, for his work on the key mechanisms that our cells use to detect and respond to low oxygen levels, known as hypoxia.

The British nephrologist, Professor Sir Peter J Ratcliffe, director of the Target Discovery Institute at the University of Oxford, member of the Ludwig Institute for Cancer Research and director of clinical research at Francis Crick Institute, London, has been awarded the Nobel Prize in Physiology or Medicine, alongside William (Bill) Kaelin, Jr of Harvard University and Gregg Semenza of Johns Hopkins University. Together they discovered the key mechanisms that our cells use to detect and respond to low oxygen levels, known as ‘hypoxia’. Throughout this work Peter has been assisted in the laboratory by many past and current members of the Renal Association, including Christopher Pugh, Patrick Maxwell, John Firth, Jonathan Gleadle, Morwenna Wood, Emma Vaux, and David Mole, as well as many nephrological colleagues from overseas.

In 1989, as a senior registrar on the Oxford renal unit at the Churchill Hospital, Peter began working on how kidney cells produce erythropoietin in response to low tissue oxygenation, with support from John Ledingham, Des Oliver, Christopher Winearls and David Weatherall. Together with work in Gregg Semenza’s laboratory and others, this led to the identification of oxygen-sensitive regulatory elements within the erythropoietin gene together with the hypoxia-inducible factors (HIFs) that bound them and regulated erythropoietin production. However, every cell in the body needs oxygen to function and survive and altered oxygen levels are central to the pathogenesis of a wide-range of diseases most notably solid tumours and ischaemic vascular disease. Peter and his team have shown that the oxygen-sensitive pathway that regulates erythropoietin operates universally in all cells, controlling many hundreds of genes with vital and diverse roles in oxygen homeostasis. Importantly, HIFs are constitutively activated in clear cell kidney cancer as a result of mutation in the VHL tumour suppressor. This insight allowed the groups led by Peter and Bill Kaelin to jointly elucidate the fine molecular mechanisms by which oxygen regulates this pathway. These have proven to be eminently targetable by small molecular compounds, with profound implications for treating a wide range of medical conditions, including renal anaemia and cancer.

Over the last 30 years, Peter has made outstanding contributions to our understanding of the basic science of cellular oxygen-sensing. He has managed to do this while continuing to practise as a nephrologist and general physician in the NHS as well as heading the Nuffield Department of Medicine. This has given him a unique perspective on his work, allowing him to both learn from his patients as well as to understand the potential benefits of his findings to them. As such, he provides an exemplary example and an inspiration to scientists and clinicians in all fields. His recognition by the Nobel Assembly is hugely deserved.

 

With thanks to Dr David Mole for this article.