Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Semenza, Gregg L.
Location Johns Hopkins University
Primary Field Medical Genetics, Hematology and Oncology
Secondary Field Medical Physiology and Metabolism
 Election Citation
Semenza is a leader in unraveling the molecular basis of the hypoxia response. He identified and isolated the first transcriptional regulator of hypoxia, HIF-1, which activates genes involved in glycolysis, erythropoiesis, and angiogenesis. His studies of hypoxia have influenced diverse fields, including vascular biology, metabolic homeostasis, and cancer research.
 Research Interests
We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. HIF-1 expression increases exponentially as cellular O2 concentration declines. HIF-1 is required for embryonic development of the circulatory system. In postnatal life, HIF-1 activates the transcription of genes that are essential for adaptive responses to hypoxia, such as glycolysis, erythropoiesis, and angiogenesis. We are presently investigating the role of HIF-1 in the pathophysiology of cancer and cardiovascular disease, which are the major causes of mortality in the U.S. population. We have demonstrated that aging and diabetes inhibit HIF-1 activity, thereby blocking ischemia induced angiogenesis. We have constructed an adenoviral vector encoding a constitutively active form of HIF-1 and demonstrated that it can stimulate vascularization of ischemic tissue and thereby overcome the effects of aging and diabetes. We have identified several drugs that potently inhibit HIF-1 activity and block the growth and vascularization of human tumor xenografts in nude mice. Clinical trials to test these agents in cancer patients are currently being organized.

 
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