Robert Turesky, BSc, PhD

Professor, Department of Medicinal Chemistry

Robert Turesky

Contact Info

PhD, Nutrition and Food Science, MIT

BSc, Biochemistry, University of Massachusetts

Summary

Turesky Lab Group

The Turesky laboratory seeks to understand the roles of long-term exposures of environmental toxicants and endogenous electrophiles to causative factors for human diseases including cancer. We use human cell lines, primary cells, tissues and biological fluids to investigate the toxicity of carcinogens, characterize their metabolic pathways, and their ability to form DNA and protein adducts in humans. There are several chemicals present in the diet, tobacco smoke, and in traditional medicinal herbs that are the focus of our investigations. The laboratory employs state-of-the-art-mass spectrometry methods to conduct metabolic and biomarker studies in humans.

Heterocyclic aromatic amines (HAAs) are potential human carcinogens formed in cooked meat and some arise in tobacco smoke. The chemistry of HAA adduct formation with DNA and blood proteins is under study, to develop biomarkers for human cohorts designed to address the role of these chemicals in the diet and the risk of developing cancer. Our goal is to see if differences in dietary habits or metabolic processing of HAAs and their ensuing DNA and protein adducts, can be employed to better understand chemical exposures interindividual susceptibilities.

Aristolochic acids are nitrophenanthrene derivatives present in herbs of Aristolochia, some of which are still found in traditional herbal remedies. A long-sought analytical method employing archived biopsy samples fixed in formalin and paraffin embedded (FFPE) tissues was established for measuring DNA damage, by mass spectrometric methods, of renal cancer patients exposed to aristolochic acid, a potent urothelial carcinogen present in some traditional Chinese medicines. This analytical approach allows us to retrospectively screen DNA damage in FFPE tissues for which there is a clinical diagnosis of cancer. We are exploring the versatility of this DNA retrieval method by examination of FFPE samples for DNA adducts associated with hazardous chemicals in cigarette smoke, cooked meats, and air pollution.

DNAand protein adductomics. Novel scanning approaches, by ion trap mass and high resolution accurate mass spectrometry, are under development to screen human biospecimens for a variety of DNA and blood protein adducts formed with carcinogens present in the diet and environment. These screening methods are expected to provide us with a better understanding of the major chemical exposures that damage the genome and proteins, and lead to the onset of diseases including cancer.

Exfoliated urinary cells are being used to develop and characterize DNA adduct biomarkers that may help to explain the origin or urinary tract cancers in tobacco smokers.

Expertise

Metabolism, Biomarkers, Mass spectrometry

Awards & Recognition

  • Scientific Advisory Board of the United States Environmental Protection Agency from 2016 – 2017
  • Chosen as Distinguished Foreign Scientist, Cover Issue, “Novel aromatic amine mutagens, unintentionally formed from azo dyes, in river water in Kyoto” Japanese Journal of Cancer Research, 1998 Sep;89(9): Inside front cover. PubMed PMID: 9818020, 1998
  • B.Sc., Magna cum laude, in Biochemistry, University of Massachusetts, Amherst., 1978

Research

Publications

Pubmed Bibliography

  • Isin EM, Turesky RJ. Introduction: Mass Spectrometry and Emerging Technologies for Biomarker Discovery in the Assessment of Human Health and Disease.Chem Res Toxicol. 2016 Dec 19;29(12):1901-1902. PMID: 27989143
  • Wang Y, Villalta PW, Peng L, Dingley K, Malfatti MA, Turteltaub KW, Turesky RJ. Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6 phenylimidazo[4,5-b]pyridine and Albumin in Humans. Chem Res Toxicol. 2017 Feb 20;30(2):705-714. doi: 10.1021/ acs.chemrestox.6b00426. Epub 2017 Jan 18.
  • Bellamri M, Le Hegarat L, Turesky RJ, Langouët S. Metabolism of the Tobacco Carcinogen 2-Amino-9H-pyrido[2,3-b]indole (A?C) in Primary Human Hepatocytes. Chem Res Toxicol. 2017 Feb 20;30(2):657-668. doi: 10.1021/acs.chemrestox.6b00394. Epub 2016 Dec 15. PMID: 27976871
  • Bellamri M, Le Hegarat L, Vernhet L, Baffet G, Turesky RJ, Langouët S. Human T lymphocytes bioactivate heterocyclic aromatic amines by forming DNA adducts. Environ Mol Mutagen. 2016 Dec;57(9):656-667. doi: 10.1002/em.22059. Epub 2016 Nov 1. PMID: 27801952
  • Guo J, Turesky RJ. Human Biomonitoring of DNA Adducts by Ion Trap Multistage Mass Spectrometry. Curr Protoc Nucleic Acid Chem. 2016 Sep 1;66:7.24.1-7.24.25. doi: 10.1002/cpnc.12. PMID: 27584705
  • Hoang ML, Chen CH, Chen PC, Roberts NJ, Dickman KG, Yun BH, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA. Aristolochic Acid in the Etiology of Renal Cell Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016 Dec;25(12):1600-1608. Epub 2016 Aug 23.
  • Le Marchand L, Yonemori K, White KK, Franke AA, Wilkens LR, Turesky RJ. Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: a feeding study. Carcinogenesis. 2016 Jul;37(7):685-91. doi: 10.1093/carcin/bgw049. Epub 2016 Apr 25. PMID: 27207666
  • Guo J, Yun BH, Upadhyaya P, Yao L, Krishnamachari S, Rosenquist TA, Grollman AP, Turesky RJ. Multiclass Carcinogenic DNA Adduct Quantification in Formalin-Fixed Paraffin-Embedded Tissues by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry. Anal Chem. 2016 May 3;88(9):4780-7. doi: 10.1021/acs.analchem.6b00124. Epub 2016 Apr 15. PMID: 27043225
  • Cai T, Yao L, Turesky RJ. Bioactivation of Heterocyclic Aromatic Amines by UDP Glucuronosyl transferases. Chem Res Toxicol. 2016 May 16;29(5):879-91. doi: 10.1021/acs.chemrestox.6b00046. Epub 2016 Apr 18. PMID: 27032077
  • Sheng J, Wang Y, Turesky RJ, Kluetzman K, Zhang QY, Ding X. Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.Chem Res Toxicol. 2016 May 16;29(5):797-809. doi: 10.1021/acs.chemrestox.5b00529. Epub 2016 Apr 14. PMID: 27028147
  • Pathak KV, Chiu TL, Amin EA, Turesky RJ. Methemoglobin Formation and Characterization of Hemoglobin Adducts of Carcinogenic Aromatic Amines and Heterocyclic Aromatic Amines. Chem Res Toxicol. 2016 Mar 21;29(3):255-69. doi: 10.1021/acs.chemrestox.5b00418. Epub 2016 Feb 22. PMID: 26824300
  • Kim S, Guo J, O'Sullivan MG, Gallaher DD, Turesky RJ. Environ Mol Mutagen. Comparative DNA adduct formation and induction of colonic aberrant crypt foci in mice exposed to 2-amino-9H-pyrido[2,3-b]indole, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, and azoxymethane. 2016 Mar;57(2):125-36. doi: 10.1002/em.21993. Epub 2016 Jan 6. PMID: 26734915
  • Turesky RJ, Yun BH, Brennan P, Mates D, Jinga V, Harnden P, Banks RE, Blanche H, Bihoreau MT, Chopard P, Letourneau L, Lathrop GM, Scelo G. Aristolochic acid exposure in Romania and implications for renal cell carcinoma. Br J Cancer. 2016 Jan 12;114(1):76-80. doi: 10.1038/bjc.2015.402. Epub 2015 Dec 10. PMID: 26657656
  • Turesky RJ, Konorev D, Fan X, Tang Y, Yao L, Ding X, Xie F, Zhu Y, Zhang QY. Effect of Cytochrome P450 Reductase Deficiency on 2-Amino-9H-pyrido[2,3-b]indole Metabolism and DNA Adduct Formation in Liver and Extrahepatic Tissues of Mice. Chem Res Toxicol. 2015 Dec 21;28(12):2400-10. doi: 10.1021/ acs.chemrestox.5b00405. Epub 2015 Dec 3. PMID: 26583703
  • Konorev D, Koopmeiners JS, Tang Y, Franck Thompson EA, Jensen JA, Hatsukami DK, Turesky RJ. Measurement of the Heterocyclic Amines 2-Amino-9H-pyrido[2,3-b]indole and 2-Amino-1-methyl-6 phenylimidazo[4,5-b]pyridine in Urine: Effects of Cigarette Smoking. Chem Res Toxicol. 2015 Dec 21;28(12):2390-9. doi: 10.1021/acs.chemrestox.5b00401. Epub 2015 Dec 3. PMID: 26574651
  • Bouvard V, Loomis D, Guyton KZ, Grosse Y, Ghissassi FE, Benbrahim-Tallaa L, Guha N, Mattock H, Straif K; Carcinogenicity of consumption of red and processed meat. International Agency for Research on Cancer Monograph Working Group. Lancet Oncol. 2015 Dec;16(16):1599-600. doi: 10.1016/S1470-2045(15)00444-1. Epub 2015 Oct 29. PMID: 26514947
  • Gruppi F, Hejazi L, Christov PP, Krishnamachari S, Turesky RJ, Rizzo CJ. Characterization of nitrogen mustard formamidopyrimidine adduct formation of bis(2-chloroethyl) ethylamine with calf thymus DNA and a human mammary cancer cell line. Chem Res Toxicol. 2015 Sep 21;28(9):1850-60. doi: 10.1021/acs.chemrestox.5b00297. Epub 2015 Sep 1.PMID: 26285869
  • Turesky RJ, White KK, Wilkens LR, Le Marchand L. Caffeine Cytochrome P450 1A2 Metabolic Phenotype Does Not Predict the Metabolism of Heterocyclic Aromatic Amines in Humans. Chem Res Toxicol. 2015 Aug 17;28(8):1603-15. doi: 10.1021/acs.chemrestox.5b00177. Epub 2015 Aug 6. PMID: 26203673
  • Yun BH, Sidorenko VS, Rosenquist TA, Dickman KG, Grollman AP, Turesky RJ. New Approaches for Biomonitoring Exposure to the Human Carcinogen Aristolochic Acid. Toxicol Res (Camb). 2015 Jul 1;4(4):763-776. PMID: 26366284
  • Yun BH, Yao L, Jelakovi? B, Nikoli? J, Dickman KG, Grollman AP, Rosenquist TA, Turesky RJ. Formalin-Fixed Paraffin Embedded Tissue as a Source for Quantitation of Carcinogen DNA Adducts: Aristolochic Acid as a Prototype Carcinogen. Carcinogenesis..35 no.9 pp.2055–2061, 2014 PubMed PMID: 24776219.
  • Peng L, Turesky RJ. Optimizing proteolytic digestion conditions for the analysis of serum albumin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a potential human carcinogen formed in cooked meat. J Proteomics. 2014 May 30;103:267-78. doi: 10.1016/j.jprot.2014.03.023. Epub 2014 Mar 31. PubMed PMID: 24698664.
  • Balbo S, Turesky RJ, Villalta PW. DNA adductomics. Chem Res Toxicol. 2014 Mar 17;27(3):356-66. doi: 10.1021/tx4004352. Epub 2014 Feb 25. PubMed PMID: 24437709;PubMed Central PMCID: PMC3997222.
  • Hoang ML, Chen CH, Sidorenko VS, He J, Dickman KG, Yun BH, Moriya M, Niknafs N, Douville C, Karchin R, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med. 2013 Aug 7;5(197):197ra102. doi: 10.1126/scitranslmed.3006200. PubMed PMID: 2392620
  • Nauwelaërs G, Bellamri M, Fessard V, Turesky RJ, Langouët S. DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl areformed at environmental exposure levels and persist in human hepatocytes. Chem Res Toxicol. 2013 Sep 16;26(9):1367-77. doi: 10.1021/tx4002226. Epub 2013 Aug 16. PubMed PMID: 23898916.
  • Yun BH, Rosenquist TA, Nikoli? J, Dragi?evi? D, Tomi? K, Jelakovi? B, Dickman KG, Grollman AP, Turesky RJ. Human formalin-fixed paraffin-embedded tissues: anuntapped specimen for biomonitoring of carcinogen DNA adducts by mass spectrometry. Anal Chem. 2013 May 7;85(9):4251-8. doi: 10.1021/ac400612x. Epub2013 Apr 10. PubMed PMID: 23550627.
  • Tang Y, Kassie F, Qian X, Ansha B, Turesky RJ (2013) DNA adduct formation of 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in Mouse Liver and extrahepatic tissues during a subchronic feeding study. Toxicol. Sci. 2013 Jun;133(2):248-58. doi: 10.1093/toxsci/kft077. Epub 2013 Mar 27. PubMed Central PMCID: PMC3663563.
  • Peng L, Turesky RJ (2012) Trapping labile sulfenamide and sulfinamide serum albumin adducts of carcinogenic arylamines by chemical oxidation (2013) Anal Chem. 2013 Jan15;85(2):1065-72. doi: 10.1021/ac3028273. Epub 2012 Dec 28. PubMed PMID:23240913; PubMed Central PMCID: PMC3621984.
  • Turesky RJ, Liu L, Wilkens LR, Le Marchand L (2013) Biomonitoring the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in hair: impact of exposure, hair pigmentation, and cytochrome P450 1A2 phenotype. Cancer Epidemiol Biomarkers Prev. 2013 Mar;22(3):356-64. doi: 10.1158/1055-9965.EPI-12-1206. Epub 2013 Jan17. PubMed PMID: 23329727; PubMed Central PMCID: PMC3610405.
  • Peng L, Dasari S, Tabb DL, Turesky RJ. Mapping Serum Albumin Adducts of the Food-Borne Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by Data-Dependent Tandem Mass Spectrometry. Chem Res Toxicol. 2012 Oct 15;25(10):2179-93. doi: 10.1021/tx300253j. Epub 2012 Aug 14.PubMed [citation] PMID: 22827630
  • Gu D, Neuman ZL, Modiano JF, Turesky RJ. Biomonitoring the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in canine fur. J Agric Food Chem. 2012 Sep 12;60(36):9371-5. doi: 10.1021/jf302969h. Epub 2012 Aug 29.PubMed [citation] PMID: 22906298
  • Englert NA, Turesky RJ, Han W, Bessette EE, Spivack SD, Caggana M, Spink DC, Spink BC. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region. Biochem Pharmacol. 2012 Sep 1;84(5):722-35. doi: 10.1016/j.bcp.2012.06.013. Epub 2012 Jun 21.PubMed [citation] PMID: 22728919
  • Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, Pu YS, Grollman AP.Aristolochic acid-associated urothelial cancer in Taiwan. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8241-6. Epub 2012 Apr 9.PubMed [citation] PMID: 22493262, PMCID: PMC3361449
  • Yun BH, Rosenquist TA, Sidorenko V, Iden CR, Chen CH, Pu YS, Bonala R, Johnson F, Dickman KG, Grollman AP, Turesky RJ. Biomonitoring of aristolactam-DNA adducts in human tissues using ultra-performance liquid chromatography/ion-trap mass spectrometry. Chem Res Toxicol. 2012 May 21;25(5):1119-31. Epub 2012 May 4.PubMed [citation] PMID: 22515372
  • Tang Y, LeMaster DM, Nauwelaërs G, Gu D, Langouët S, Turesky RJ. UDP-glucuronosyltransferase-mediated metabolic activation of the tobacco carcinogen 2-amino-9H-pyrido[2,3-b]indole. J Biol Chem. 2012 Apr 27;287(18):14960-72. Epub 2012 Mar 5.PubMed [citation] PMID: 22393056, PMCID: PMC3340249
  • Jelakovic´ B, Karanovic´ S, Vukovi c´-Lela I, Miller F, Edwards KL, Nikolic´ J, Tomic, K, Slade N, Brdar B, Turesky RJ, Stipanic´D, Dittrich D, Grollman AP, Dickman,KG. Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. Kidney Int. 2012 Mar;81(6):559-67. doi: 10.1038/ki.2011.371. Epub 2011 Nov 9.PubMed [citation] PMID: 22071594 PMC3361449
  • Turesky RJ, Bessette EE, Dunbar D, Liberman RG, Skipper PL. CytochromeP450-mediated metabolism and DNA binding of 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline and its carcinogenic isomer 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in mice.Chem Res Toxicol. 2012 Feb 20;25(2):410-21. Epub 2011 Dec 28.PubMed [citation] PMID: 22118226, 22118226, PMC: 3531872
  • Gu D, Turesky RJ, Tao Y, Langouët SA, Nauwelaërs GC, Yuan JM, Yee D, Yu MC. DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 4-aminobiphenyl are infrequently detected in human mammary tissue by liquid chromatography/tandem mass spectrometry. Carcinogenesis. 2012 Jan;33(1):124-30. Epub 2011 Nov 9. PubMed [citation] PMID: 22072616, PMCID: PMC3276332
  • Peng L, Turesky RJ. Mass spectrometric characterization of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine N-oxidized metabolites bound at Cys34 of human serum albumin. Chem Res Toxicol. 2011 Nov 21;24(11):2004-17. Epub 2011 Oct 4.PubMed [citation] PMID: 21916490, PMCID: PMC3221794
  • Turesky RJ, Le Marchand L.Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol. 2011 Aug 15;24(8):1169-214. Epub 2011 Jun 20. Review.PubMed [citation] PMID: 21688801, PMCID: PMC3156293