Skip Navigation

Find a Doctor

Find a Researcher

Researchers

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

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

Research Interests

Protection of the heart against ischemia -reperfusion injury; Role of HIF-1 in cancer; Gene and stem cell therapy for ischemic cardiovascular disease; Molecular mechanisms of oxygen homeostasis; Genetic syndromes due to mutations in genes encoding transcription factors ...read more

Background

Dr. Gregg L. Semenza is a professor of 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 of Pediatrics 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 genes in response to changes in oxygen availability. The finding has far-reaching implications in understanding and treating low-oxygen health conditions such as coronary artery disease and tumor growth.

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

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

Dr. Semenza’s research interests include the molecular mechanisms of oxygen homeostasis; gene and stem cell therapy for ischemic cardiovascular disease; the role of HIF-1 in cancer; and protection of the heart against ischemia-reperfusion injury. He has authored more than 250 research articles and several book chapters, and has been cited in research more than 30,000 times.

He 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. He serves on the editorial board of several journals, including Molecular and Cellular Biology and Cancer Research, and is editor-in-chief of the Journal of Molecular Medicine.

In 2012, Dr. Semenza was elected to the Institute of Medicine. He has been recognized with numerous other awards, including the Lefoulon-Delalande Grand Prize from the Institut de France, the Gairdner Award, the Stanley J. Korsmeyer Award, the E. Mead Johnson Award for Research in Pediatrics, the Jean and Nicholas Leone Award from the Children''s Brain Tumor Foundation, the Established Investigator Award from the American Heart Association, and the Lucille P. Markey Scholar Award in Biomedical Science.

...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

Research & Publications

Research Summary

The Semenza lab studies molecular mechanisms underlying angiogenesis and vascular remodeling in ischemic cardiovascular disease. A major aspect of this process is the production of multiple angiogenic cytokines and growth factors in response to hypoxia/ischemia, which is mediated by the transcription factor HIF-1 (hypoxia-inducible factor 1). HIF-1 mediates vascular and progenitor cell responses to angiogenic signals, but these processes are impaired by aging and diabetes. The team currently is studying the use of gene and stem cell therapy in mouse models of critical limb ischemia and cutaneous burn wounds.


HIF-1 plays important roles in critical aspects of cancer biology, including tumor angiogenesis, regulation of glucose and energy metabolism, invasion, and metastasis. The team is taking several approaches to inhibit HIF-1 activity, including RNA interference, dominant negative constructs, and small molecule inhibitors. A major focus of their current cancer research is using animal, cell-based, molecular, and biophysical approaches to investigate the role of HIF-1 in vascular and lymphatic metastasis of human breast cancer.


HIF-1 also is required for ischemic preconditioning, short episodes of ischemia and reperfusion that protect the heart against a subsequent prolonged ischemic insult. The team currently is exploring the cellular and molecular mechanisms underlying ischemic preconditioning using mice in which HIF-1 activity has been knocked out in specific cell types within the heart.


The team now is using mass spectroscopy techniques to identify proteins that interact with the HIF-1 subunit. By employing this taking proteomics-based approach, they have identified novel regulators of HIF-1 transcriptional activity as well as direct regulation of the DNA replication machinery by HIF-1.

Lab

Dr. Semenza’s lab is currently investigating: 

{line break}
    {line break}
  1. Molecular mechanisms of oxygen homeostasis. They have 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 role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, chronic lung disease, and diabetes.
  2. {line break}
  3. Gene and stem cell therapy for ischemic cardiovascular disease. They are performing preclinical studies to investigate the use of adenoviral vectors encoding a constitutively active form of the HIF-1 subunit to stimulate vascularization of ischemic tissue. They are also utilizing bone marrow-derived angiogenic cells and adipose-derived mesenchymal stem – cells to stimulate vascularization and tissue regeneration in preclinical models of peripheral arterial disease.
  4. {line break}
  5. Role of HIF-1 in cancer. They are investigating the effects of altered HIF-1 activity on tumor growth, metabolism, and vascularization in preclinical models. These studies are providing proof-of-principle that inhibition of HIF-1 activity represents a novel strategy of cancer therapy. They have identified several drugs that potently inhibit HIF-1 and block the growth and vascularization of human tumor xenografts in nude mice.
  6. {line break}
  7. Protection of the heart against ischemia-reperfusion injury. They have demonstrated in preclinical models that recombinant human erythropoietin induces dramatic acute protection against cell death in hearts subjected to ischemia and reperfusion via activation of the phosphatidylinositol-3-kinase signal-transduction pathway. They have shown that HIF-1 is required for ischemic preconditioning.
  8. {line break}

Lab Website: Gregg Semenza Lab

Clinical Trials

HIF-1 Regulated Endothelial Progenitor Cell (EPC) Recruitment in Burn Wound Healing

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: 3361.

Semenza GL.  Targeting HIF-1 for cancer therapy.  Nat. Rev. Cancer 3, 721-732 (2003). Citations: 3342. 

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: 2334.

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: 1713.

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: 1646.

Contact for Research Inquiries

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

Patient Ratings & Comments

The Patient Rating score is an average of all responses to physician related questions on the national CG-CAHPS Medical Practice patient experience survey through Press Ganey. Responses are measured on a scale of 1 to 5, with 5 being the best score. Comments are also gathered from our CG-CAHPS Medical Practice Survey through Press Ganey and displayed in their entirety. Patients are de-identified for confidentiality and patient privacy.

  • ...Loading ratings...
  • ... 
  • ... 
  • ... 
  • ... 
  • ... 

Comments

Loading...
Is this you? Edit Profile
back to top button