Biological Engineering

John S. Wishnok
Senior Research Scientist, 56-747B
Phone: 617- 253-6795
Fax: 617-252-1787

wishnok@mit.edu

Wishnok/Tannenbaum Mass Spectrometry Lab.

Administrative Assistant:    Amy Francis   amyvf@mit.edu
Phone: 617-253-6792   Fax: 617-252-1787

Current Research 

Biology and biological engineering are being increasingly driven by advances in bioanalytical techniques and instrumentation. My research is focused on applications of biological mass spectrometry for the characterization and quantitation of DNA and protein damage caused by exposure both to xenobiotic substances and to endogenous compounds that are formed during various metabolic pathways. In the case of xenobiotics, e.g., smoking-related or diet-related carcinogens, quantitation of modifications to DNA or proteins can provide estimates of individual exposure to the active forms of these substances. DNA or protein modifications arising from endogenous substances, e.g., peroxynitrite, can provide valuable clues towards the biochemistry of their formation and often towards the subtle but important balances between essential vs damaging levels of nominally normal metabolites.


Recent and Selected Publications: 

J.C. Delaney, L. Smeester, C. Wong, K. Taghizadeh, J.S. Wishnok, C.L. Drennan, L.D. Samson, and J.M. Essigmann. AlkB reverses DNA damage caused by lipid oxidation in vitro and in vivo. Nature Struct. Molecul. Biol., 18, 855-860(2005).

M.H. Choi, P.L. Skipper, J.S. Wishnok, and S.R. Tannenbaum. Characterization of testosterone 11-[beta]-hydroxylation catalyzed by human liver cytochromes P450. Drug Metab. Dispos., 33, 714-8 (2005).

D. Farkas, V.B. Bhat, S. Mandapati, J.S. Wishnok, and S.R. Tannenbaum. Characterization of the secreted proteome of rat hepatocytes cultured in collagen sandwiches. Chem. Res. Toxicol., 18, 1132-1139 (2005).

J.Niles, J.S.Wishnok and S.R. Tannenbaum. Spiroiminodihydantoin and guanidinohydantoin are the dominant products of 8-oxoguanosine oxidation at low fluxes of peroxynitrite: kinetic and mechanistic studies with 18O. Chem. Res. Toxicol. 17, 1510-1519 (2004).

J.Niles, J.S.Wishnok and S.R. Tannenbaum. Mass Spectrometric Identification of 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid during Oxidation of 8-oxoguanosine by Peroxynitrite and KHSO5/CoCl2. Chem. Res. Toxicol. 17, 1501-1509 (2004).

H.Yu, J. Niles, J.S. Wishnok, S.R.Tannenbaum. Spirodihydantoin is a minor product of 5-hydroxyisourate in urate oxidation. Org Lett. 6, 3417-3420 (2004).

P.L. Skipper, B.J. Hughey, R.G. Liberman, M.H. Choi, J.S. Wishnok, R.E. Klinkowstein, R.E. Shefer, and S.R. Tannenbaum. Bringing AMS into the Bioanalytical Chemistry Lab. IN: Nuclear Instruments and Methods in Physics Research – B. Proceedings of the AMS-9 Conference. Nucl. Instr. Meth .Phys. Res. B. 223-224, 740-744 (2004).

B.J. Hughey, P.L. Skipper, J.S. Wishnok, R.E. Shefer, N.A. Fried, J.T. Mehl, and S.R. Tannenbaum. Sample introduction interface for analytical processing. U.S. Patent No. 6,867,415 (2004).

Joseph M. Lee, Jacquin C. Niles, John S. Wishnok, and Steven R. Tannenbaum. Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines. Chem. Res. Toxicol., 15, 7-17 (2002).

Jacquin C. Niles, John S. Wishnok, and Steven R. Tannenbaum. A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2’,3’,5’-tri-O-acetyl-guanosine. J. Am. Chem. Soc., 49, 12147-12151 (2001).

John T. Mehl, Paul L. Skipper, Steven R. Tannenbaum, John S. Wishnok, Barbara J. Hughey, Robert E. Klinkowstein, and Ruth E. Shefer. GC and LC interfaces for biological AMS. Proceedings of the 7th International Symposium on the Synthesis and Applications of Isotopes and Isotopically Labelled Compounds. Dresden, Germany, June 2000. In press. (2001).

Kaisheng Jiao, Saraswathi Mandapati, Paul L. Skipper, Steven R. Tannenbaum, and John S. Wishnok. Site-selective nitration of tyrosine in human serum albumin by peroxynitrite. Anal. Biochem., 293, 43-52 (2001).

Natalia Tretyakova, Brock Matter, Alexis Ogdie, John S. Wishnok, and Steven R. Tannenbaum. Locating nucleobase lesions within DNA sequences by MALDI-TOF mass spectral analysis of exonuclease ladders. Chem. Res. Toxicol., 14, 1058-1070 (2001).

Jacquin C. Niles, John S. Wishnok, and Steven R. Tannenbaum. Spiroiminohydantoin is the major product of the 8-oxo-7-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue. Organic Letters, 3, 963-966 (2000).

Barbara J. Hughey, Paul L. Skipper, Robert E. Klinkowstein, Ruth E. Shefer, John S. Wishnok, and Steven R. Tannenbaum. Low-energy biomedical GC-AMS system for 14C and 3H detection. Nuclear. Inst. Methods Phys. Res. B., 172, 40-46 (2000).

Natalia Y. Tretyakova, Samar Burney, Burcak Pamir, John S. Wishnok, Peter C. Dedon, Gerald N. Wogan, and Steven R. Tannenbaum. Peroxynitrite-induced DNA damage in the supF gene: correlation with the mutational spectrum. Mutat Res., 447, 287-303 (2000).

Natalia Y. Tretyakova, John S. Wishnok, and Steven R. Tannenbaum. Peroxynitrite-induced secondary oxidative lesions at guanine nucleobases: chemical stability and recognition by the Fpg DNA repair enzyme. Chem. Res. Toxicol., 13, 658-664 (2000).

Jacquin C. Niles, Samar Burney, Sukhjeet P. Singh, John S. Wishnok, and Steven R. Tannenbaum. Peroxynitrite reaction products of 3',5'-di-O-acetyl-8-oxo-7,8-dihydro-2'-deoxyguanosine. Proc. Natl. Acad. Sci. USA., 96, 11727-11734 (1999).

Lacreis C. Kidd, W.G. Stillwell, Mimi C. Yu, John S. Wishnok, Paul L. Skipper, Ronald K. Ross, Brian E. Henderson, and Steven R. Tannenbaum. Urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in White, African-American, and Asian-American men in Los Angeles County. Cancer Epidemiol. Biomarkers Prev., 8, 439-445 (1999).