Congratulations to William Kaelin, Peter Ratcliffe, and Gregg Semenza for winning the 2019 Nobel Prize in Physiology or Medicine for their groundbreaking work uncovering how cells respond to hypoxia.
Oxygen is essential for life, and it has long been understood that large organisms require adequate oxygen levels in organs and tissues to support cellular metabolism and bioenergetics. This year’s Nobel Prize-winning trio each contributed substantially to discovering how cells and tissues respond to low oxygen conditions, and the subsequent molecular mechanisms that ensure oxygen homeostasis is maintained.
Hypoxia triggers a wide range of physiological changes at the cellular, tissue, and organismal levels such as changes in cellular metabolism, increased blood vessel formation, and erythropoiesis. As uncovered by Sir Peter Ratcliffe and Dr. Semenza, the hypoxia-inducible factor, HIF1α, is central to coordinating transcriptional changes that mediate response to low oxygen in all cells and tissues. Dr. Kaelin’s work in the familial cancer disease von Hippel–Lindau (VHL) syndrome subsequently revealed how defects in regulating HIF-α via the VHL protein caused the richly vascularized tumors that are characteristic of this cancer. Work from all three investigator’s laboratories spurred the development of an entire field devoted to understanding how organisms adapt to changes in oxygen availability. These processes are fundamental for development and physiological homeostasis, and they are dysregulated in diseases including cancer, cardiovascular disease, pulmonary hypertension, and stroke.
From left to right: William Kaelin, Peter Ratcliffe, and Gregg Semenza discovered the essential pathway by which human and animal cells sense and adapt to changes in oxygen availability. Image credits (left to right): Sam Ogden/Dana-Farber Cancer Institute, Paul Wilkinson Photography, Jay VanRensselaer/Johns Hopkins Medicine.
Jillian H. Hurst