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Gregg L. Semenza, M.D., Ph.D.

Headshot of Gregg L. Semenza
  • Director, Vascular Program, Institute for Cell Engineering
  • Professor of Genetic Medicine

Research Interests

Molecular Mechanisms of Oxygen Homeostasis; Role of Hypoxia-Inducible Factors in Cancer Progression ...read more

Background

Dr. Gregg L. Semenza is a professor of genetic medicine, pediatrics, radiation oncology, and molecular radiation sciences, biological chemistry, medicine, and oncology at the Johns Hopkins University School of Medicine. Dr. Semenza is the C. Michael Armstrong Professor and serves as the director of the vascular program at the Institute for Cell Engineering.

One of today’s preeminent researchers on the molecular mechanisms of oxygen regulation, Dr. Semenza has led the field in uncovering how cells adapt to changing oxygen levels. He is best known for his ground-breaking discovery of the HIF-1 (hypoxia-inducible factor 1) protein, which controls changes in gene expression in response to changes in oxygen availability. The discovery of HIF-1 has far-reaching implications for understanding and treating conditions, such as cancer and ischemic cardiovascular disease, in which hypoxia plays an important role in disease pathogenesis.

Dr. Semenza was recognized for this groundbreaking research in 2019, when he was awarded the Nobel Prize in Physiology or Medicine with William G. Kaelin, Jr., M.D. of the Dana-Farber Cancer Institute, and Peter J. Ratcliffe of Oxford University.

Dr. Semenza received his A.B. from Harvard University. He earned M.D. and Ph.D. degrees from the University of Pennsylvania, completed residency training in pediatrics at Duke University Medical Center, and postdoctoral training in medical genetics at Johns Hopkins. Dr. Semenza joined the Johns Hopkins faculty in 1990.

Dr. Semenza’s research interests include investigating the molecular mechanisms of oxygen homeostasis; the role of HIF-1 in cancer and blinding eye diseases associated with ocular neovascularization; and the development of drugs that inhibit HIF-1 as a treatment for these disorders. His lab's research has been published in more than 400 research articles and book chapters, which have been cited more than 150,000 times.

Dr. Semenza is a founding fellow of the American College of Medical Genetics and was elected to the Association of American Physicians and the National Academy of Sciences in 2008. In 2012, Dr. Semenza was elected to the National Academy of Medicine. He has been recognized with numerous other awards, including the Lefoulon-Delalande Grand Prize from the Institut de France, Canada Gairdner International Award, Stanley J. Korsmeyer Award, E. Mead Johnson Award for Research in Pediatrics, Jean and Nicholas Leone Award from the Children's Brain Tumor Foundation, Established Investigator Award from the American Heart Association, Massry Prize, Wiley Prize in Biomedical Sciences, and the Albert Lasker Basic Medical Research Award. He serves as Deputy Editor of the Journal of Clinical Investigation.

...read more

Titles

  • Director, Vascular Program, Institute for Cell Engineering
  • Professor of Genetic Medicine
  • Professor of Biological Chemistry
  • Professor of Medicine
  • Professor of Oncology
  • Professor of Pediatrics
  • Professor of Radiation Oncology and Molecular Radiation Sciences

Departments / Divisions

Centers & Institutes

Education

Additional Training

Ph.D., University of Pennsylvania, 1984

M.D., University of Pennsylvania, 1984

A.B., Harvard University, 1978

American Board of Medical Genetics, 1990

Research & Publications

Research Summary

  1. Molecular mechanisms of oxygen homeostasis. The Semenza lab purified, cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. HIF-1 expression increases exponentialåy as cellular O2 concentration declines. HIF-1 activates transcription of genes that are essential for adaptive responses to hypoxia, such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. They are presently investigating the molecular mechanisms by which HIF-1 activates transcription of target genes using chromatin immunoprecipitation-mass spectrometry, RNA interference, RNA sequencing and other techniques to identify proteins that are recruited by HIF-1 to hypoxia response elements to activate gene transcription.
  2. Role of HIF-1 in cancer. The Semenza lab is investigating the effects of altered HIF-1 activity on tumor growth, metabolism, vascularization, invasion/metastasis, cancer stem cell specification and immune evasion in preclinical models. These studies are providing proof-of-principle that inhibition of HIF-1 activity represents a novel strategy of cancer therapy. The lab identified several drugs that potently inhibit HIF-1 and block cancer progression in mouse models. The lab is utilizing multiple drug discovery strategies to identify novel HIF inhibitors and testing their efficacy in various cancer types.
  3. Role of HIF-1 in ocular neovascularization. In collaboration with the laboratory of Dr. Akrit Sodhi at the Wilmer Eye Institute, the Semenza lab is testing novel HIF inhibitors for their efficacy in blocking choroidal and retinal neovascularization in mouse models of blinding eye diseases.
  4. Role of HIF-1 in sleep apnea-associated hypertension and impaired glucose homeostasis. In collaboration with the laboratory of Prof. Nanduri Prabhakar at the University of Chicago, the Semenza lab is investigating the role of HIF-1 in activation of the sympathetic nervous system in response to intermittent hypoxemia associated with sleep apnea.

Lab

Dr. Semenza’s lab is currently investigating: 

  1. Molecular mechanisms of oxygen homeostasis. The Semenza lab purified, cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. HIF-1 expression increases exponentialåy as cellular O2 concentration declines. HIF-1 activates transcription of genes that are essential for adaptive responses to hypoxia, such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. They are presently investigating the molecular mechanisms by which HIF-1 activates transcription of target genes using chromatin immunoprecipitation-mass spectrometry, RNA interference, RNA sequencing and other techniques to identify proteins that are recruited by HIF-1 to hypoxia response elements to activate gene transcription.
  2. Role of HIF-1 in cancer. The Semenza lab is investigating the effects of altered HIF-1 activity on tumor growth, metabolism, vascularization, invasion/metastasis, cancer stem cell specification and immune evasion in preclinical models. These studies are providing proof-of-principle that inhibition of HIF-1 activity represents a novel strategy of cancer therapy. The lab identified several drugs that potently inhibit HIF-1 and block cancer progression in mouse models. The lab is utilizing multiple drug discovery strategies to identify novel HIF inhibitors and testing their efficacy in various cancer types.
  3. Role of HIF-1 in ocular neovascularization. In collaboration with the laboratory of Dr. Akrit Sodhi at the Wilmer Eye Institute, the Semenza lab is testing novel HIF inhibitors for their efficacy in blocking choroidal and retinal neovascularization in mouse models of blinding eye diseases.
  4. Role of HIF-1 in sleep apnea-associated hypertension and impaired glucose homeostasis. In collaboration with the laboratory of Prof. Nanduri Prabhakar at the University of Chicago, the Semenza lab is investigating the role of HIF-1 in activation of the sympathetic nervous system in response to intermittent hypoxemia associated with sleep apnea.

Lab Website: Gregg Semenza Lab

Clinical Trials

 

Selected Publications

View all on PubMed

Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA 92: 5510-5514 (1995). Citations: 6521.

Semenza GL.  Targeting HIF-1 for cancer therapy.  Nat. Rev. Cancer 3, 721-732 (2003). Citations: 6763. 

Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.  Mol. Cell. Biol. 16:4604-4613 (1996).Citations: 4277.

Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW.  Overexpression of hypoxia-inducible factor 1 in common human cancers and their metastases. Cancer Res. 59:5830-5835 (1999). Citations: 3288.

Semenza GL, Wang GL.  A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.  Mol. Cell. Biol. 12:5447-5454 (1992). Citations: 3353.

Contact for Research Inquiries

Email me Phone: 443-287-5619

Academic Affiliations & Courses

Graduate Program Affiliation

Cellular and Molecular Medicine
Human Genetics and Molecular Biology

Activities & Honors

Honors

  • Research Professor, American Cancer Society, 2012
  • Lefoulon-Delalande Grand Prize, Institut de France, 2012
  • Elected to the Institute of Medicine, 2012
  • Stanley J. Korsmeyer Award, American Society for Clinical Investigation, 2012
  • Canada Gairdner Award, 2010
  • Member, National Academy of Sciences USA, 2008
  • Member, Association of American Physicians, 2008
  • E. Mead Johnson Award for Research in Pediatrics, Society for Pediatric Research, 2000
  • Jean and Nicholas Leone Award, Children''s Brain Tumor Foundation, 1999
  • Member, American Society for Clinical Investigation, 1995
  • Established Investigator Award, American Heart Association, 1994
  • Member, Society for Pediatric Research, 1991
  • Lucille P. Markey Scholar Award in Biomedical Science, Markey Trust, 1989
  • Alpha Omega Alpha Honor Medical Society, 1981
  • Nobel Prize in Physiology or Medicine, 2019
  • Albert Lasker Basic Medical Research Award, 2016, 2016
  • Wiley Prize in Biomedical Sciences, 2014
  • Massry Prize, 2018
  • AHA Distinguished Scientist Award, American Heart Association, 2020

Memberships

  • Fellow, American Association for Cancer Research Academy, 2020
  • Founding Fellow, American College of Medical Genetics, 1993
  • Association of American Physicians, 2008
  • National Academy of Sciences, 2008
  • National Academy of Medicine, 2012

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