Biological Engineering

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

wishnok@mit.edu

Wishnok/Tannenbaum Mass Spectrometry Lab.

Administrative Assistant:    Marcia Ross   mross@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. 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. Current projects include development of a nitrosothiol-specific fluorescent probe for visualizing nitric-oxide-related biomolecule modifications in brain tissue, a search for predictive or prognistic biomarkers of inflammatory bowel disease, and defining drug metabolism, metabolomics, and proteomics in a complex microphysiological system based on human cell cultures.


Recent and Selected Publications: 


Alison Darby, Kvin Lertpiriyapong, Ujjal Sarkar,Uthpala Seneviratne, Danny S. Park, Eric R.Gamazon, Chara Batchelder, Cheryl Cheung, Ellen M. Buckley, Nancy S. Taylor, Zeli Shen, Steven R. Tannenbaum, John S. Wishnok, and James G. Fox. 2014. Cytotoxic and pathogenic properties of Klebsiella oxytoca isolated from laboratory animals. PLoS One. 2014 Jul 24;9(7):e100542. eCollection .PMID: 25057966

Kun Lu, Rashid Mahbub, Peter H. Cable, Hongyin Ru, Nicola M. Parry, Wanda M. Bodnar, John S. Wishnok, Miroslav Styblo, James A. Swenberg, James G. Fox, and Steven R. Tannenbaum. 2014. Gut microbiome phenotypes driven by host genetics affect arsenic metabolism. Chem Res Toxicol. Feb 17;27(2):172-4. Epub 2014 Feb 3. PMID: 24490651

Kun Lu, Ryan P. Abo, Katherine A. Schlieper, Michelle E. Graffam, Stuart Levine, John S. Wishnok, James A. Swenberg, Steven R. Tannenbaum, and James G. Fox. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health Perspect. Mar;122:284-9 1Epub 2014 Jan 9. PMID: 24413286 [PubMed - in process]

Yong Ak Song, Wu L, Tannenbaum SR, Wishnok JS, Han J. Tunable membranes for free-flow zone electrophoresis in PDMS microchip using guided self-assembly of silica microbeads. 2013. Anal Chem. 2013 Dec 17;85(24):11695-9. Epub 2013 Nov 25. PMID:24251795

Uthpala Seneviratne , Luiz C. Godoy, John S. Wishnok, Gerald N. Wogan, and Steven R. Tannenbaum. 2013. Mechanism-based triarylphosphine-ester probes for capture of endogenous RSNOs. J. Am .Chem. Soc., 135, 7693-7704. Epub 2013 May 8.

Charles G. Knutson, Aswin Mangerich, Yu Zeng, Arek R. Raczynski , Rosa G Liberman , Pilsoo Kang, Wenjie Ye, Erin G. Prestwich, Kun Lu John S. Wishnok, Joshua R. Korzenik, Gerald N Wogan, James G. Fox, Peter C. Dedon, and Steven R.Tannenbaum. 2013. Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease. Proc Natl Acad Sci USA., 110, E2332-E2341. Epub 2013 Jun 10. PMID: 23754421

Kun Lu, Peter H.Cable, Abo RP, Hongyin Ru, Michelle E. Graffam, Katherine A. Schlieper, Nicola M. Parry, Stuart Levine, Wanda M. Bodnar, John S. Wishnok, Miroslav Styblo, James A. Swenberg, James G. Fox, and Steven R. Tannenbaum. 2013. Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation. Chem Res Toxicol. Dec 16;26(12):1893-1903 Epub 2013. PMID: 24134150

Kok Seong Lim, Koli Taghizadeh, John S. Wishnok, Ramesh B. Indrikanti, Vladimir Shafirovich, Nicholas E. Geacintov and Peter C. Dedon. 2012. Sequence-dependent Variation in the Reactivity of 8-Oxo-7,8-dihydro-2’-deoxyguanosine toward Oxidation. Chem. Res. Toxicol., 25, 366-373. PMID: 23057664

Aswin Mangerich, Charles G. Knutson, Nicola M. Parry, Sureshkumar Muthupalani, Wenjie Ye, Erin Prestwich, Liang Cui., Jose L. McFaline, M. Mobley, Zhongming Ge, Koli Taghizadeh, John S.Wishnok, Gerald N. Wogan, James G. Fox, Steven R. Tannenbaum, and PeterC. Dedon. 2012. Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer. Proc. Natl. Acad. Sci. USA, 109, E1820-E1829. [Epub ahead of print]. PMID: 22689960

Katherine T. Barglow, Charles G. Knutson, John S. Wishnok, Steven R. Tannenbaum, and Michael A. Marletta. 2011. Site-specific and redox-controlled S-nitrosation of thioredoxin.PNAS Plus, 108, E600-606. PMID: 21849622

Peter J. Slade, Michelle V. Williams, Alison Chiang, Elizabaeth Iffrig, Steven R. Tannenbaum, and John S. Wishnok. 2011. A filtered database search algorithm for endogenous serum protein carbonyl modifications in a mouse model of inflammation. Mol. Cell Proteomics, 10, M111.007658. Epub Aug 17.

Yong-Ak Song, Michael Chan, Chris Celio, Steven R. Tannenbaum, John S. Wishnok, and Jeongyun Han. 2010. Free-flow zone electrophoresis of peptides and proteins in PDMS microchip for a narrow pI range sample prefractionation coupled with mass spectrometry. Anal. Chem., 82, 2317-2325. PMID: 25057966

Peter J. Slade, Michelle V. Williams, Viral Brahmbhatt, Ajit Dash, John S. Wishnok, and Steven R. Tannenbaum. 2010. Proteins modified by the lipid peroxidation aldehyde 9,12-dioxo-10(E)-dodecenoic acid in MCF7 breast cancer cells. Chem. Res. Toxicol., 23, 557-567.PMID: 21769395

Tessa E. North, Ramesh B. Indrikanti, L.M. Vedder, A.M. Lord, John S. Wishnok, Steven R. Tannenbaum, Leonard .I. Zon, and Wolfram Goessling. 2010. PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc. Natl. Acad. Sci. USA, 107, 17315-17320.PMID: 20855591

Dora Il'yasova, Bridget J. McCarthy, Serap Erdal, Joanna Shimek, Jennifer Goldstein, Daniel R. Doerge, Steven R. Myers, Paolo Vineis, John S. Wishnok, James A. Swenberg, Darrell D. Bigner, and Faith G. Davis. Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology. J. Toxicol. Environ. Health B. Crit. Rev., 12, 175-187 (2009).

Anna L. Stevens, John S. Wishnok, Forest M. White, Alan J. Grodzinsky, and Steven R. Tannenbaum. Mechanical injury and cytokines cause loss of cartilage integrity and upregulate proteins associated with catabolism, immunity, inflammation, and repair. Mol. Cell Proteomics, 8, 1475-1489 (2009).

Anna L. Stevens, John S. Wishnok, Diana H. Chai, Alan J. Grodzinsky, and Steven R. Tannenbaum. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis-liquid chromatography tandem mass spectrometry analysis of bovine cartilage tissue response to mechanical compression injury and the inflammatory cytokines tumor necrosis factor a and interleukin-1 ß. Arthritis Rheum., 58, 489-500 (2008).

Michelle V. Williams, John S. Wishnok, and Steven R. Tannenbaum. Covalent adducts arising from the decomposition products of lipid hydroperoxides in the presence of cytochrome C. Chem. Res. Toxicol., 20, 767-775 (2007).

Lianrong Wang, S. Chen , T. Xu, Koli Taghizadeh, John S. Wishnok,, Xinfeng Zhou, D. You, Z. Deng, and Peter C. Dedon. Phosphorothioation of DNA in bactera by dnd genes. Chem. Res. Toxicol., 20, 1730-1736 (2007).

Monica Kristiansson, Vadiraja Bhat, I. Ramesh Babu, John S. Wishnok, and Steven .R. Tannenbaum. Comparative time-dependent analysis of potential inflammation biomarkers in lymphoma-bearing SJL mice. J. Proteome Res., 6, 1735-1744 (2007).

Bo Pang, Xinfeng Zhou, Hongbin Yu, Min Dong, Koli Taghizadeh, John S. Wishnok, Steven R. Tannenbaum, and Peter C. Dedon. Lipid peroxidation dominates the chemistry of DNA adduct formation in a mouse model of inflammation. Carcinogenesis, 28, 1807-1813 (2007).
Michelle V. Williams, John S. Wishnok, and Steven R. Tannenbaum. Covalent adducts arising from the decomposition products of lipid hydroperoxides in the presence of cytochrome C. Chem. Res. Toxicol., 20, 767-775 (2007).

Beatriz Zayas, W.G. Stillwell, John S. Wishnok, Laura J. Trudel, Paul L. Skipper, John M. Essigmann, and Robert G. Croy. Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients. Carcinogenesis., 28, 342-349 (2007).

Shawn M. Hillier, John C. Marquis, Beatriz Zayas, John S. Wishnok, Rosa G. Liberman, Paul L. Skipper, Steven R. Tannenbaum, John M. Essigmann, and Robert G. Croy. DNA adducts formed by a novel antitumor agent 11beta-dichloro in vitro and in vivo. Mol. Cancer Ther., 5, 977-984 (2006).

Hyun Gyung Jang, Misun Park, John S. Wishnok, Steven R. Tannenbaum, and Gerald N. Wogan. Hydroxyl specific fluorescence labeling of ABP-deoxyguanosine, PhIP-deoxyguanosine, and AFB1-formamidopyrimidine with BODIPY-FL. Anal. Biochem., 359, 151-160 (2006).

Jacquin C. Niles, John S. Wishnok and Steven R. Tannenbaum. Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide, 14, 109-121 (2006).

Alex Garcia, Carlos J. Bosques, John S. Wishnok, Yan Feng, B.J. Karalius, J.R. Butterton, David B. Schauer, Arlin B. Rogers, and James G. Fox. Renal injury is a consistent finding in Dutch Belted rabbits experimentally infected with enterohemorrhagic Escherichia coli. J. Infect. Disease., 193, 1125-1134 (2006).

Barbara J. Hughey, Paul L. Skipper, John S. Wishnok, Ruth E. Shefer, Naomi A. Fried, John T. Mehl, and Steven R. Tannenbaum. Sample introduction interface for analytical processing. U.S. Patent No. 6,867,415.

Barbara J. Hughey, Paul L. Skipper, John S. Wishnok, Ruth E. Shefer, John T. Mehl, and Steven R. Tannenbaum. Sample Introduction Interface for Analytical Processing of a Sample Placed on a Substrate. U.S. Patent No. 6,707,035

Vadiraja B. Bhat, Man Ho Choi, J.S. Wishnok, and Steven R. Tannenbaum. Comparative plasma proteome analysis of lymphoma-bearing SJL mice. J. Proteome. Res., 4, 1814-1825 (2005).

Hongbin Yu, Lata Venkatarangan, John S. Wishnok, and Steven R. Tannenbaum. Quantitation of four oxidation products from reaction of DNA with varying doses of peroxynitrite. Chem. Res. Toxicol., 18, 1849-1857 (2005).

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

Man Ho Choi, Paul L. Skipper, John 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).

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

Jacquin Niles, John S.Wishnok and Steven 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).

Jacquin C. Niles, John S.Wishnok and Steven 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).

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

Paul L. Skipper, Barbara J. Hughey, Rosa G. Liberman, M.H. Choi, John S. Wishnok, Robert E. Klinkowstein, Ruth E. Shefer, and Steven 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).

Jennifer L. Caulfield, John S. Wishnok, and Steven R. Tannenbaum. Nitric oxide-induced interstrand cross-links in DNA. Chem Res Toxicol., 16 571-574, (2003).

Feng Gu, Sara Stillwell, John S. Wishnok, Anthony J. Shallop, Roger A. Jones, and Steven R. Tannenbaum. Peroxynitrite-induced reactions of synthetic oligo 2'-deoxynucleotides and DNA containing guanine: formation and stability of a 5-guanidino-4-nitroimidazole lesion. Biochemistry, 23, 7508-7518. (2002).

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, 7-14 (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).

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).

Kaushik Mitra ,John C. Marquis, Shawn Hillier, Peter T. Rye, Beatriz Zayas, A.S. Lee, John M. Essigmann, and Robert G. Croy A rationally designed genotoxin that selectively destroys estrogen receptor-positive breast cancer cells. J. Amer. Chem. Soc., 124, 1862-1863 (2001).

Jinping Gan, Paul L. Skipper, and Steven R. Tannenbaum. Oxidation of 2,6-dimethylaniline by recombinant human cytochrome P450s and human liver microsomes. Chem. Res. Toxicol., 14, 672-677 (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 (2001).

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).