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

Director, Program in Vascular Cell Engineering - Institute for Cell Engineering

Professor - Department of Pediatrics and Institute of Genetic Medicine

Dr. Semenza has identified 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 expression and activity are regulated by hydroxylaton of proline and asparagine residues, a novel O2-dependent post-translational modification.

1974

Harvard College, Cambridge, MA

1978

A.B., Biology, magna cum laude
Thesis: Somatic cell genetic mapping: Electrophoretic studies of human and
murine glutathione peroxidase expression in hybrid somatic cells

1978

University of Pennsylvania, Philadelphia, PA

1984

M.D., Ph.D. in Genetics
Thesis: Molecular genetic analysis of the silent carrier of ß thalassemia

1984

Internship and Residency in Pediatrics

1986

Duke University Medical Center, Durham, NC

1986

Postdoctoral Fellowship in Medical Genetics

1990

The Johns Hopkins University School of Medicine, Baltimore, MD

1985

Diplomate of the National Board of Medical Examiners

1989

Diplomate of the American Board of Pediatrics

1990

Diplomate of American Board of Medical Genetics

1990

Licensed Physician, State of Maryland

1992

Founding Fellow of the American College of Medical Genetics

1981

Alpha Omega Alpha Honor Medical Society

1989

Lucille P. Markey Scholar Award in Biomedical Science

1994

Established Investigator Award, American Heart Association

1998

Students’ Choice Visiting Professor, Dept. of Physiology, Med. Coll. of Wisconsin

1999

Jean and Nicholas Leone Award, Children’s Brain Tumor Foundation

2000

E. Mead Johnson Award for Research in Pediatrics

2001

Iyengar Memorial Lecturer, University of Pennsylvania School of Veterinary Medicine

2001

Abelson Memorial Visiting Professor, Washington University School of Medicine

2001

Woznicki Lecturer in Cardiovascular Pathology & Genetics, Baylor College of Medicine

2002

Chancellor’s Award in Neuroscience, Louisiana State University Health Sciences Center

2003

7th Annual Fisher Distinguished Lecturer, Tulane University School of Medicine

1. Bos, R., van der Hoeven, J. J. M., van der Wall, E., van der Groep, P., van Diest, P. J., Comans, E. F. I., Yoshi, U., Semenza, G. L., Hoekstra, O. S., Lammertsma, A. A., and Molthoff, C. F. M. Biological correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J. Clin. Oncol. 20, 379-387 (2002).

2. Kline, D. D., Peng, Y., Manalo, D. J., Semenza, G. L., and Prabhakar, N. R. Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1?. Proc. Natl. Acad. Sci. USA 99, 821-826 (2002).

3. Kojima, H., Gu, H., Nomura, S., Caldwell, C. C., Kobata, T., Carmeliet, P., Semenza, G. L., and Sitkovsky, M. V. Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1? deficient chimeric mice. Proc. Natl. Acad. Sci. USA 99, 2170-2174 (2002).

4. Cargile, C. B., Goh, D. L., Goodman, B. K., Chen, X. N., Korenberg, J. R., Semenza, G. L., and Thomas, G. H. Molecular cytogenetic characterization of a subtle interstitial del(3)(p25.3p26.2) in a patient with deletion 3p syndrome. Am. J. Med. Genet. 109, 133-138 (2002).

5. Treins, C., Giorgetti-Peraldi, S., Murdaca, J., Semenza, G. L., and Van Obberghen, E. Insulin stimulates HIF-1 through a PI-3-kinase/TOR dependent signaling pathway. J. Biol. Chem. 277, 27975-27981 (2002).

6. Fukuda, R., Hirota, K., Fan, F., Jung, Y. D., Ellis, L. M., and Semenza, G. L. IGF-1 induces HIF-1 mediated VEGF expression that is dependent on MAP kinase and PI-3-kinase signaling in colon cancer cells. J. Biol. Chem. 277, 38205-38211 (2002).

7. Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., Maxwell, P., Stockton, D. W., Semenza, G. L., and Prchal, J. T. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat. Genet. 32, 614-621 (2002).

8. Janssen, H. L., Haustermans, K. M., Sprong, D., Blommestijn, G., Hofland, I., Hoebers, F. J., Blijweert, E., Raleigh, J. A., Semenza, G. L., Varia, M. A., Balm, A. J., van Velthuysen, M. L., Delaere, P., Sciot, R., and Begg, A. C. HIF-1?, pimonidazole, and iododeoxyuridine to estimate hypoxia and perfusion in human head-and-neck tumors. Int. J. Radiat. Oncol. Biol. Phys. 54, 1537-1549 (2002).

9. Semenza, G. L. HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol. Med. 8 , S62-S67 (2002).

10. Semenza, G. L. Involvement of hypoxia-inducible factor 1 in human cancer. Intern. Med. 41, 79-83 (2002).

11. Semenza, G. L. Physiology meets biophysics: visualizing the interaction of hypoxia-inducible factor 1? with p300 and CBP. Proc. Natl. Acad. Sci. USA 99, 11570-11572 (2002)

12. Semenza, G. L. Signal transduction to hypoxia-inducible factor 1. Biochem. Pharmacol. 64, 993-998 (2002).

13.Semenza, G. L. Homeostatic regulation by hypoxia-inducible factor 1. Science & Medicine, 336-345 (2002).

14. Buchler, P., Reber, H. A., Buchler, M., Shrinkante, S., Buchler, M. W., Friess, H., Semenza, G. L., and Hines, O. J. Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer. Pancreas 26, 56-64 (2003).

15. Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., Iyer, N., LaRusch, J., Pak, B., Taghavi, P. and Semenza, G. L. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 63, 1138-1143 (2003).

16. Bos, R., van der Groep, P., Greijer, A. E., Shvarts, A., Meijer, S., Pinedo, H. M., Semenza, G. L., van Diest, P. J., and van der Wall, E. Levels of hypoxia-inducible factor 1??independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 97: 1573-1581 (2003).

17. Fukuda, R., Kelly, B., and Semenza, G. L. Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Cancer Res. 63: 2330-2334 (2003).

18. Cai, Z., Manalo, D. J., Wei, G., Rodriguez, E. R., Fox-Talbot, K., Lu, H., Zweier, J. L., and
Semenza, G. L. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation 108: 79-85 (2003).

19. Stoeltzing, O., Liu, W., Reinmuth, N., Fan, F., Parikh, A. A., Bucana, C. D., Evans, D. B.,
Semenza, G. L., and Ellis, L. M. Regulation of hypoxia-inducible factor 1?, vascular endothelial growth factor, and angiogenesis by an insulin-like growth factor-1 receptor autocrine loop in human pancreatic cancer. Am. J. Pathol. 163: 1001-1011 (2003).?

20. Kelly, B. D., Hackett, S. F., Hirota, K., Oshima, Y., Cai, Z., Berg-Dixon, S., Rowan, A., Yan, Z., Campochiaro, P. A., and Semenza, G. L. Cell-type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in non-ischemic tissue by a constitutively-active form of hypoxia-inducible factor 1. Circ. Res., in press (2003).

21. Kasuno, K., Takabuchi, S., Fukuda, K., Kizaka-Kondoh, S., Yodoi, J., Adachi, T., Semenza, G.L., and Hirota, K. Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling. J. Biol. Chem., in press (2003).

22. Semenza, G. L. Genomics of oxygen sensing. In: Oxygen Sensing: Responses and Adaptation to Hypoxia (S. Lahiri, G. L. Semenza, N.R. Prabhakar, Ed.), Marcel Dekker, Inc., New York, 1-6 (2003).

23. Semenza, G. L. Transcription factors and human disorders. In: Encyclopedia of the Human Genome, Macmillan Publishers, Ltd. (2003).

24. Semenza, G. L. Angiogenesis in ischemic and neoplastic disorders. Annu. Rev. Med. 54, 17-28 (2003).

25. Semenza, G. L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3, 721-732 (2003).

26. Semenza, G. L. The HIF-1 family of bHLH-PAS proteins: master regulators of oxygen homeostasis. In: PAS Proteins: Regulators and Sensors of Development and Physiology (S. T. Crews, Ed.), Kluwer Academic Publishers, Boston, 183-204 (2003).

27. Semenza, G. L. Oxygen-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. J. Appl. Physiol., in press.