William Kaelin

What makes William Kaelin a Global Shaker?

William Kaelin was a joint winner of the 2019 Nobel Prize in Physiology or Medicine for unravelling a molecular mechanism that is not only crucial to survival but is also entwined with cancer and other diseases.

Along with Peter J. Ratcliffe of the University of Oxford and the Francis Crick Institute and Gregg L. Semenza of the Johns Hopkins University School of Medicine, Kaelin was awarded the prize for his seminal contributions to the discovery of the molecular pathway used by all multicellular organisms to sense and adapt to changes in oxygen levels.

Kaelin and co. deciphered the core molecular events that explain how almost all multi-cellular animals tune their physiology to cope with varying quantities of life-sustaining oxygen in a unique signalling scheme. Their findings could lead to new therapeutics for a wide range of disorders — including cancer, cardiovascular disease, anaemia, and macular degeneration.

This oxygen-sensing mechanism involves the tumour-suppressor protein VHL, which is mutated in many kidney cancers, and proteins known as hypoxia-inducible factors, HIF-1α and HIF-2α. Kaelin showed that HIF-2α drives certain kidney cancers and recently discovered how HIF-1α is hijacked by triple-negative breast cancers.

Kaelin’s research into how mutations in tumour-suppressor genes can lead to cancer` was first focused on a rare, hereditary syndrome called von Hippel-Lindau disease, caused by defects in the tumour-suppressor gene VHL.

By 1996, Kaelin had shown that cells lacking the VHL gene and its associated protein were incapable of sensing oxygen.

Over the next several years, he and others shed light on the function of VHL, including the finding that cells lacking VHL protein were unable to degrade HIF-1-alpha, a protein that is a master regulator of the cellular response to low oxygen levels, and revealed the molecular details of this mechanism.

Kaelin is developing therapeutic strategies for targeting these molecules and others implicated in cancer, such as mutated enzymes IDH1 and IDH2, with designer drugs.

William G. Kaelin Jr. currently acts as the Sidney Farber Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute, senior physician in medicine at Brigham and Women’s Hospital and Howard Hughes Medical Institute Investigator,

Last updated: February 5, 2020

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