Johns Hopkins University School of Medicine, USA
Dr. Semenza is the C. Michael Armstrong professor of genetic medicine, with joint appointments in pediatrics, radiation oncology, biological chemistry, medicine, and oncology at the Johns Hopkins University School of Medicine. He serves as the founding director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering and the founding director of the Armstrong Oxygen Biology Research Center.
Dr. Semenza received an A.B. (in Biology) from Harvard University and M.D. and Ph.D. (in Genetics) degrees from the University of Pennsylvania. He completed pediatrics residency training at Duke University Medical Center and postdoctoral training in medical genetics at Johns Hopkins. He has been a member of the Johns Hopkins faculty in 1990.
Dr. Semenza’s lab discovered hypoxia-inducible factor 1 (HIF-1), a transcription factor that controls the expression of thousands of genes in response to changes in oxygen availability, for which he was awarded the 2019 Nobel Prize in Physiology or Medicine. His current research interests include investigating the molecular mechanisms of oxygen homeostasis and the role of HIF-1 in cancer progression. He has authored more than 450 research articles and book chapters, and his work has been cited by other scientists more than 175,000 times. Dr. Semenza is co-founder of HIF Therapeutics Inc., which is focused on the development of HIF inhibitors for the treatment of cancer and blinding eye diseases.
In addition to the Nobel Prize, Dr. Semenza has received the Albert Lasker Basic Medical Research Award (2016), Wiley Prize in Biomedical Sciences (2014), Lefoulon-Delalande Grand Prize from the Institut de France (2012), and the Canada Gairdner International Award (2010).
Cancer cells are characterized by high metabolic demand. Oxygen serves as a key substrate in cellular metabolism and bioenergetics. Hypoxia or low oxygen abundance is a common feature of the tumor microenvironment that occurs due to an imbalance between O2 supply and demand. Many of the metabolic responses to hypoxia, which affect levels of glucose, glutamine, glycogen, and lipids, are orchestrated by hypoxia-inducible factors (HIFs), which are O2-regulated transcription factors composed of an O2-labile HIF-α subunit and a constitutively expressed HIF-1β subunit. Increased expression of HIF-1α protein or increased expression of HIF target genes in primary tumor biopsies is associated with increased patient mortality in many types of cancer. HIFs activate the transcription of genes involved in angiogenesis, cancer stem cell specification, immune evasion, invasion and metastasis as well as metabolism. The mechanisms and consequences of homeostatic responses mediated by the HIFs that modulate tumor metabolism will be discussed.