Professor, Department of Pediatrics, Medicine, Oncology, and Radiation Oncology
A.B., Harvard, 1978
M.D., University of Pennsylvania, 1984
Ph.D., University of Pennsylvania, 1984
Main Interests:
Molecular Mechanisms of Oxygen Homeostasis. 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 activates transcription of genes that are essential for adaptive responses to hypoxia such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. We are presently investigating the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S. population.
Research Interests:
1. Molecular Mechanisms of Oxygen Homeostasis. 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 activates transcription of genes that are essential for adaptive responses to hypoxia such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. We are presently investigating the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S. population.
2. Gene and Stem Cell Therapy for Ischemic Cardiovascular Disease. We are performing preclinical studies to investigate the use of adenoviral vectors encoding a constitutively active form of the HIF-1ÿ subunit to stimulate vascularization of ischemic tissue. We are also utilizing endothelial progenitor cells and bone marrow stromal cells to stimulate vascularization and tissue regeneration in preclinical models of peripheral arterial disease and myocardial infarction.
3. Role of HIF-1 in Cancer. We 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.
4. Protection of the Heart Against Ischemia-Reperfusion Injury. We 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.
Clinical Activities:
- Board Certification: Founding Fellow of the American College of Medical Genetics (1992); Licensed Physician, State of Maryland (1990); Diplomate of American Board of Medical Genetics (1990); Diplomate of the American Board of Pediatrics (1989)
- Clinical Interests: Genetic syndromes due to mutations in genes encoding transcription factors Medical Genetics Clinic; Johns Hopkins Outpatient Center 8th Fl, Pediatric Specialty Clinics area 601 Noth Caroline Street Baltimore, MD 21205 Phone: 410-955-3071 Fax: 410-614-9246
- Clinic:
Medical Genetics Clinic Johns Hopkins Outpatient Center (JHOC)
8th floor, Pediatric Specialty Clinics area
601 North Caroline Street
Baltimore, MD 21205
Phone: 410-955-3071 Fax: 410-614-9246
Educational Activities:
- Preceptor: Predoctoral Training Program in Human Genetics, Medical Genetics Training Program, Graduate Program in Cellular and Molecular Medicine, Multidisciplinary Training Program in Lung Disease, Hematology Training Program, Basic Science Training in Nephrology, and Minority Summer Internship Program.
- Courses taught: Advanced Topics in Human Genetics course (Human Genetics), CMM Core Discussion Group (Cellular and Molecular Medicine), Journal Club (Human Genetics), Clinical Skills (School of Medicine), The Short Course in Medical and Experimental Mammalian Genetics (The Jackson Laboratory, Bar Harbor, ME)
- Textbook: Semenza, GL: Transcription Factors and Human Disease. Oxford University Press, New York, 1998 Links: Jackson Laboratory-Annual Short Course in Medical and Experimental Mammalian Genetics Medical Genetics (Genetic Medicine) Clinical Residencey Program and Genetic Subspecialty Postdoctoral Fellowships Predoctoral Training Program in Human Genetics
- Textbook: Semenza, GL: Transcription Factors and Human Disease. Oxford University Press, New York, 1998.
Recognition and Leadership Roles:
- Awards: E. Mead Johnson Award for Research in Pediatrics (2000); Jean and Nicholas Leone Award, Children's Brain Tumor Foundation (1999); Established Investigator Award, American Heart Association (1994); Lucille P. Markey Scholar Award in Biomedical Science (1989); Alpha Omega Alpha Honor Medical Society (1981)
- Elected Professional Societies: American Society for Clinical Investigation (1995); Society for Pediatric Research (1991)
- Editorial boards: American Journal of Physiology: Lung, Cellular, and Molecular Physiology (2000-present); Antioxidants and Redox Signaling (2003-present); Cancer Research (2003-Present); Cardiovascular Research (2003-present); Circulation Research (2003-present); Human Mutation (1992-2003); Journal of Clinical Investigation (2000-present)
- Administrative Appointment: Director, Vascular Program, The Johns Hopkins Institute for Cell Engineering (2003-present)
Publications:
- Wang GL, Jiang B-H, Rue EA, and 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. Abstract
- Forsythe, JA, Jiang, B-H, Iyer, NV, Agani, F, Leung, SW, Koos, RD, and Semenza, GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol. Cell. Biol. 16, 4604-4613, 1996. Abstract
- Winograd, J, Reilly, MP, Roe, R, Lutz, J, Laughner, E, Xu, X, Hu, L, Asakura, T, Vander Kolk, C, Strandberg, JD, and Semenza, GL: Perinatal lethality and multiple craniofacial malformations in MSX2 transgenic mice. Hum. Mol. Genet. 6, 369-379, 1997. Abstract
- Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wegner R, Gassman M, Gearhart JD, Lawler AM, Yu AY, Semenza GL: Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Deve 12:149-162, 1998. Abstract
- Yu, AY, Shimoda, LA, Iyer, NV, Huso, DL, Sun, X, McWilliams, R, Beaty, T, Sham, JSK, Wiener, CM, Sylvester, JT, and Semenza, GL: Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. J. Clin. Invest. 103, 691-696, 1999. Abstract
- Zhong, H, De Marzo, AM, Laughner, E, Lim, M, Hilton, DA, Zagzag, D, Buechler, P, Isaacs, WB, Semenza, GL, and Simons, JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59, 5830-5835, 1999. Abstract
- Ravi, R, Mookerjee, B, Bhujwalla, ZM, Sutter, CH, Artemov, D, Zeng, Q, Dillehay, LE, Madan, A, Semenza, GL, and Bedi, A: Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 14, 34-44, 2000. Abstract
- Laughner, E, Taghavi, P, Chiles, K, Mahon, PC, and Semenza, GL : HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol. Cell. Biol. 21, 3995-4004, 2001. Abstract
- Semenza, GL: HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 107, 1-3, 2001. Abstract
- Mahon, P C, Hirota, K, and Semenza, GL: FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 15, 2675-2686, 2001. Abstract
Contact Information:
Gregg L. Semenza, M.D., Ph.D.
Johns Hopkins University School of Medicine
Institute of Genetic Medicine
733 North Broadway
Broadway Research Building, Suite 671
Baltimore, MD 21205
Phone: 410-955-1619
Fax: 443-287-5618
E-Mail: gsemenz1@jhem.jhmi.edu
