The 2019 Nobel Prize honors fundamental discoveries in hypoxia response

The 2019 Nobel Prize for Physiology or Medicine was awarded to Professors Sir Peter J. Ratcliffe (University of Oxford), Gregg L. Semenza (Johns Hopkins University), and William G. Kaelin Jr. (Dana-Farber Cancer Institute) for their discoveries of a fundamental aspect of cellular physiology, the cellular sensing of oxygen levels and regulation of physiologic hypoxia. Each of these physician-scientists was intrigued by a different clinically relevant observation and utilized very basic biochemical tools to address their questions. These separate lines of investigation converged, delineating a central cellular pathway with farranging implications for human physiology, disease states, and medicine. The story of how they uncovered hypoxia response begins with a deep interest in basic human biology. Uncovering a hypoxia-inducible pathway Semenza, a pediatric geneticist, was studying the triggers for the production of erythropoietin, a hematopoietic growth factor produced by the liver and kidney that promotes the generation of red blood cells. His group identified a sequence-specific binding site (termed hypoxia-response element [HRE]) for a transcription factor in the 3 flanking region of the human erythropoietin gene (EPO). He biochemically purified the factor, which he called hypoxia-inducible factor 1 (HIF-1) (1). HIF-1 is a heterodimer composed of HIF-1a, a protein expressed in an oxygen-regulated manner, and a constitutively expressed factor, HIF-1b. This dimer formed a potent transcription factor complex, and Semenza showed that []. © 2020, American Society for Clinical Investigation.