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Michael B. Sporn, M.D.
Title(s):
Professor of Pharmacology & Toxicology and of Medicine
Department(s):
Medicine
Pharmacology and Toxicology
Education:
Harvard University, AB 1952
U. Rochester School of Medicine & Dentistry, MD 1959
Programs:
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Websites:
http://dms.dartmouth.edu/pharm-tox
http://www.dartmouth.edu/~spornlab
Contact Information:
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7650 Remsen Dept. of Pharmacology and Toxicology Dartmouth Medical School Hanover NH 03755 |
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Office: Remsen 524A Phone: 603-650-6557 Fax: 603-650-1129 Email: michael.sporn@dartmouth.edu Assistant: Megan Padgett Asst. Phone: 603-650-6559 |
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Selected Publications: |
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Liby, K., Royce, D. B., Risingsong, R., Williams, C. R., Wood, M. D., Chandraratna, R. A., and Sporn, M. B. A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland. Clin Cancer Res, 13: 6237-6243, 2007 Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer Liby, K. T., Yore, M. M., and Sporn, M. B. Nat Rev Cancer, 7: 357-369, 2007 Liby, K., Royce, D. B., Williams, C. R., Risingsong, R., Yore, M. M., Honda, T., Gribble, G. W., Dmitrovsky, E., Sporn, T. A., and Sporn, M. B. The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice. Cancer Res, 67: 2414-2419, 2007 Yore, M. M., Liby, K. T., Honda, T., Gribble, G. W., and Sporn, M. B. The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta. Mol Cancer Ther, 5: 3232-3239, 2006 Sporn, M. B. Dichotomies in cancer research: some suggestions for a new synthesis. Nat Clin Pract Oncol, 3: 364-373, 2006 |
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Professional Interests:
Chemoprevention of cancer, especially by retinoids and other ligands of the steroid receptor superfamily; peptide growth factors, especially transforming growth factor-beta (TGF-beta) and its mechanism of action; development of new natural products for prevention of cancer. Synthetic triterpenoids as anti-inflammatory, anti-oxidative, and anti-carcinogenic agents.
Dr. Sporn completed his undergraduate studies at Harvard College, majoring in biology, in 1952. He received his M.D. at the University of Rochester in 1959. Dr. Sporn then began his research career at the National Institutes of Health, where, in 1970, he was made the Head of the Lung Cancer Unit. In 1978 he became Chief of the Laboratory of Chemoprevention, where he remained until 1995, when he came to Dartmouth Medical School as the Oscar M. Cohn '34 Professor of Pharmacology and Medicine.
Triterpenoids of an ursane or oleanane structure are widely distributed in nature, occurring in hundreds of plants all over the world. Many such structures have interesting biological, pharmacological, or medicinal activities, similar to those of retinoids and steroids, including inhibition of carcinogenesis and induction of differentiation in leukemia or teratocarcinoma cells. Ursanes and oleananes belong to a larger family of related terpenoids, many of which are ligands for the steroid receptor superfamily, such as retinoids and classical steroids.
Since the biological activities of ursanes and oleananes resemble those of retinoids and many steroids, it is reasonable to suggest that there might be an intracellular receptor or receptors for ursanes and oleananes, that is a member of the steroid receptor superfamily. Although genes for numerous "orphan receptors" (members of the steroid receptor superfamily) have been cloned, ligands for many of these receptors have yet to be identified. The possibility that one or more triterpenoids may be such ligands needs to be investigated. Ursane and oleanane compounds may need to be activated in a manner analogous to the retinoids and deltanoids before they bind to an appropriate receptor. The "active" forms of vitamin A (retinol), which are the ligands for the six intracellular retinoid receptors, are all-trans-retinoic acid and 9-cis-retinoic acid. Both of these molecules are considerably more polar than dietary vitamin A (retinol or beta carotene), just as the active form of vitamin D, namely 1,25- dihydroxy-cholecalciferol is more polar than dietary vitamin D (cholecalciferol).
In a collaboration with Professor Gordon Gribble in the Department of Chemistry, we are studying ursanes and oleananes that are more polar than the common parent substances, ursolic acid and oleanolic acid. The goal of these studies is to understand the mechanism of action of triterpenoinds, and also to develop new agents for prevention of cancer and other degenerative diseases. Two of the new synthetic triterpenoids that have been made for the first time in the Department of Chemistry are now in clinical trials.
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