Michael B. Sporn, M.D.
Professor of Pharmacology & Toxicology
Professor of Medicine
Pharmacology & Toxicology
Harvard University, AB 1952
U. Rochester School of Medicine & Dentistry, MD 1959
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Dept. of Pharmacology and Toxicology
Geisel School of Medicine
Hanover NH 03755
Chemoprevention of cancer, especially by retinoids, rexinoids, 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 and rexinoids (RXR ligand) 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.
In 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 triterpenoids, and also to develop new agents for prevention of cancer and other degenerative diseases. One of the new synthetic triterpenoids that has been made for the first time in the Department of Chemistry is now in clinical trials for the treatment of advanced diabetic kidney disease. Karen Liby, Associate Professor of Pharmacology, is a key collaborator in the Sporn Lab
The rexinoids LG100268 and LG101506 inhibit inflammation and suppress lung carcinogenesis in A/J mice.
Novel synthetic pyridyl analogues of CDDO-Imidazolide are useful new tools in cancer prevention.
Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO-methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis.
PARP inhibitors for chemoprevention--reply.
A synthetic triterpenoid CDDO-Im inhibits tumorsphere formation by regulating stem cell signaling pathways in triple-negative breast cancer.
An efficient synthesis of methyl 2-cyano-3,12-dioxoursol-1,9-dien-28-oate (CDDU-methyl ester): analogues, biological activities, and comparison with oleanolic acid derivatives.
The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice.
Complete protection against aflatoxin B(1)-induced liver cancer with a triterpenoid: DNA adduct dosimetry, molecular signature, and genotoxicity threshold.
Synthesis and biological evaluation of amino acid methyl ester conjugates of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid against the production of nitric oxide (NO).
The Nrf2 triterpenoid activator, CDDO-imidazolide, protects kidneys from ischemia-reperfusion injury in mice.