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September 27, 2016

Pathways for Oxygen Regulation and Homeostasis: The 2016 Albert Lasker Basic Medical Research Award

Author Affiliations
  • 1Howard Hughes Medical Institute and Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2University of Oxford, Oxford and the Francis Crick Institute, London, United Kingdom
  • 3McKusick-Nathans Institute of Genetic Medicine and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA. 2016;316(12):1252-1253. doi:10.1001/jama.2016.12386

The 2016 Albert Lasker Basic Medical Research Award has been presented to William G. Kaelin, Peter J. Ratcliffe, and Gregg L. Semenza for the discovery and elucidation of pathways by which humans and other multicellular organisms sense and respond to changes in oxygen availability.

How Homo sapiens solve the challenge of continuously delivering oxygen to each of the 1014 cells that comprise the adult human body is central to the understanding of metazoan evolution, development, physiology, and disease pathobiology. The combined discoveries of Drs Kaelin, Ratcliffe, and Semenza have identified both the existence of a pathway that directly signals oxygen levels in cells, and its major components—the family of heterodimeric transcription factors (hypoxia-inducible factors [HIFs]) that direct the fundamental processes underpinning metazoan oxygen homeostasis—and the actual source of the oxygen-sensitive signal, a set of dioxygenase enzymes that catalyze the oxidation (hydroxylation) of HIF and regulate its oxygen-dependent destruction by the von Hippel-Lindau (VHL) ubiquitin-proteasome pathway.1-6

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