Gregg L. Semenza

Gregg L. Semenza (born 1956, New York City, New York) is an American physician and scientist known for his investigations of how cells use and regulate oxygen and for his discovery of hypoxia-inducible factor (HIF), a molecule that is activated by reduced oxygen availability in cells and that plays a critical role in enabling cells to survive in certain disease states. Semenza’s research opened a door for the investigation and development of novel treatments for diseases such as cancer and ischemic cardiovascular disease, in which reduced oxygen availability is a major feature of disease. For his discoveries he was awarded the 2019 Nobel Prize for Physiology or Medicine (shared with American scientist William G. Kaelin, Jr., and British scientist Sir Peter J. Ratcliffe).

Semenza attended Harvard University, where he studied pediatric genetics, focusing primarily on chromosomal alterations in Down syndrome, and earned a bachelor’s degree in 1978. He continued his education at the University of Pennsylvania, graduating in 1984 with medical and doctorate degrees. In 1986, having completed an internship and a residency in pediatrics at Duke University, Semenza pursued postdoctoral studies in medical genetics at Johns Hopkins University in Baltimore. He remained at Johns Hopkins for the duration of his career, joining the faculty in 1990 and establishing his own laboratory there. He later served as director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering.

In the late 1980s Semenza became curious about the mechanisms underlying cellular responses to changes in oxygen availability. Although researchers understood that a hormone known as erythropoietin was produced by cells in response to hypoxia (low-oxygen conditions), virtually nothing was known about the genetic mechanisms controlling this response. Semenza’s search for genetic factors that control how cells react to low oxygen levels led him to discover HIF. He and colleagues found that HIF directs a wide array of cellular responses to oxygen availability and, in particular, dictates responses to hypoxic conditions. Semenza observed that HIF levels increase significantly under hypoxia, whereas HIF expression is decreased under normal oxygen conditions. He subsequently investigated the role of HIF in cancer, where elevated HIF expression enables tumour cells to thrive and proliferate under hypoxic conditions, and investigated novel therapies for ischemic cardiovascular disease, which is characterized by reduced blood flow, and hence reduced oxygen delivery, to the heart.

Semenza was recognized for his work with multiple awards throughout his career. He shared the 2010 Canada Gairdner International Award and the 2016 Albert Lasker Basic Medical Research Award with Kaelin and Ratcliffe. He was an elected member of the National Academy of Sciences (2008) and the National Academy of Medicine (2012).