Steven Tannenbaum, Ph.D.
Department of Biological Engineering Division
Underwood-Prescott Professor of Toxicology
Professor of Chemistry
Professor of Biological Engineering
Ph.D. Food Science, 1962
Massachusetts Institute of Technology
Our laboratory has been interested for 30 years in the formation, distribution, and metabolism of nitrate, nitrite, and N-nitroso compounds. This work led to our discovery of the endogenous synthesis of nitrogen oxides and eventually to the discovery of nitric oxide (NO) as a biological molecule. At present, research in our laboratory is focused on the pathophysiological consequences of NO and its oxidation products, encompassing the processes of cell-mediated nitrosation, free-radical reactions and oxidation. We are particularly interested in the nature of chemical damage to DNA and its genotoxic consequences. From a health point of view, this is important for the inflammatory state and for various infections and diseases that increase the risk of cancer. We also are interested in the inhibition of these reactions by anti-oxidants and other substances that offer protection from oxidation stress.
NO is formed by many types of cells in the body for the purpose of intracellular communication (e.g., in the brain and cardiovascular system) and as part of the inflammatory response system in macrophages and endothelial cells. Paradoxically, NO has two dichotomous effects: it facilitates cell signaling in a variety of pathways, but it also contributes to disease processes such as inflammation, stroke, cancer and infection. A major focus of our research is to elucidate the role of NO in cell signaling and toxicity in order to resolve this paradox.
Role of caspase modifications in regulation apoptosis
As part of the MIT Cell Decision Processes Center, we are collaborating with the Samson laboratory to study caspase post translational modifications and their role in apoptosis-survival decisions. The caspases are a class of enzymes that are involved in apoptosis signal cascades. The inactive caspase pro-enzyme is activated by proteolytic cleavage in a process that can be inhibited by phosphorylation and NO-mediated nitrosation, and these modifications are thought to be pivotal events in initiating and executing apopotosis. We are developing sensitive and specific mass spectrometry-based methods to quantify phosphorylation, nitrosation and cleavage by several of the 14 known caspases in human cells.
Other studies of NO-dependent cell processes
- Understanding how compounds such as cytokines, insulin and glucosamine alter the spectrum of NO effects by modulating signal networks.
- Examining the mechanisms by which NO affects kinase signaling through oxidation, nitrosation of protein sulfhydryl groups and release of metal ions.
- Using proteomics to study post translational modifications of proteins involved in NO signaling pathways that are involved in cancer, arthritis and infection.
- Examining the role of NO-induced DNA damage in carcinogenesis and how cells respond to this damage.
- Elucidating the role of NO in cell and cartilage inflammation reactions that can give rise to osteoarthritis and rheumatoid arthritis.
- C. Li, T.L. Wright, M. Dong, Y.E.M.Dommels, L.J. Trudel, P.C. Dedon, S.R. Tannenbaum, G.N. Wogan. 2005. Biological role of glutathione in nitric oxide-induced toxicity in cell culture and animal models. Free Radical Biology & Medicine 39, 1489-1498.
- A.Sivaraman, J.K.Leach, S. Townsend, T. Lida, B.J. Hogan, D.B.Stolz, R.Fry, L.D.Samson, S.R.Tannenbaum, LG.Griffin 2005. A Microscale in vitro Physiological Model of the Liver: Predictive Screens for Drug Metabolism and Enzyme Induction. Current Drug Metabolism. 6 (6), 569-591.
- S. R. Tannenbaum and Ji-Eun Kim 2004. Controlled S-nitrosation. Nat. Chem. Bio. 1(2), 2-3.
- J.Niles, J.S.Wishnok and S.R. Tannenbaum 2005.Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. EPub ahead of print.. Nitric Oxide.
- H. Yu, L. Venkatarangan, J.S.Wishnok and S.R. Tannenbaum 2005. Quantitation of Four Oxidation Products from Reaction of DNA with Varying Doses of Peroxynitrite. Chem. Res.Toxicol. Dec 18 (12): 1849-57.
- V. Bhat, M.H. Choi, J.S. Wishnok and S.R. Tannenbaum 2005. Comparative Plasma Proteome Analysis of Lymphoma-Bearing SJL Mice. Journal of Proteome Research. 4 (5), 1814-25.
- J. Kim, S.R.Tannenbaum, and F. White. 2005 Global phosphoproteome of HT-29 Human Colon Adenocarcinoma Cells. Journal of Proteome Research. 4,1339-1346.
- D. Farkas and S.R.Tannenbaum 2005. Characterization of Chemically Induced Hepatotoxicity in Collagen Sandwiches of Rat Hepatocytes. Toxicological Sciences. 85,927-34
Last Updated: April 16, 2008