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Dr. John Groopman

Ph.D.
Interests

Public Health-Based Cancer Prevention Strategies

Titles

Professor of Environmental Health Sciences,The Johns Hopkins Bloomberg School of Public Health
Joint Appointment in Oncology

Schools\Degrees

PhD., Massachusetts Institute of Technology, Cambridge, MA

Training

Massachusetts Institute of Techology, National Cancer Institute, NIH, Laboratory of Human Carcinogensis, Cambridge, MA

Research Summary

Dr. Groopman’s main research goals are in the development of molecular biomarkers reflective of exposure, early disease, and risk from environmental carcinogens. The environmental carcinogens studied include agents that are naturally occurring in the diet produced as a result of cooking practices and agents that are prevalent in urban environments. A major emphasis of the research has been in the elucidation of the role of aflatoxins, a common contaminate of the food supply, in the induction of liver cancer in high-risk populations in Asia and sub-Saharan Africa. This work has led to the identification of a very strong chemical-viral interaction between aflatoxin and the human hepatitis B virus (HBV) in the induction of liver cancer. This research forms the foundation for the use of aflatoxin biomarkers as intermediate endpoints in the development of chemoprevention strategies for these high-risk people. This work has led to major collaborations involving chemoprevention clinical trials using both primary and secondary prevention strategies. Recently, these studies have been expanded to involve the investigation of mutations in the HBV genome as an enhancer of the cancer risk from aflatoxin exposure. 

In addition to the aflatoxin biomarker, Dr. Groopman has been actively involved in the development of biomarkers of exposure to the potent class of heterocyclics that are colon and prostate carcinogens in experimental models. These compounds are being investigated as potential etiologic agents in colon and prostate cancer. Research has also been ongoing to develop mass spectroscopic methods for the detection of mutated oncogenes, tumor-suppressor genes, and other somatic mutations in biofluids that can be used in molecular diagnostic methods.

Finally, work has been ongoing to characterize exposure to environmental carcinogens and other host-susceptibility factors that contribute to the very high rates of cancer in Baltimore City. Thus, the research in our laboratory focuses on the translation of mechanistic research to public-health-based prevention strategies.

 

EM 5/06
 

Journal Citations

Bodreddigari, S., Jones, L.K., Egner, P.A., Groopman, J.D., Sutter, C.H., Roebuck, B.D., Guengerich, F.P., Kensler, T.W., and Sutter, T.R. (2008). Protection against aflatoxin B1-induced cytotoxicity by expression of the cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3. Chem Res Toxicol 21, 1134-1142.

Bransfield, L.A., Rennie, A., Visvanathan, K., Odwin, S.A., Kensler, T.W., Yager, J.D., Friesen, M.D., and Groopman, J.D. (2008). Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urine. Chem Res Toxicol 21, 1622-1630.

Chen, J. G., S. Y. Kuang, P. A. Egner, J. H. Lu, Y. R. Zhu, J. B. Wang, B. C. Zhang, T. Y. Chen, A. Munoz, T. W. Kensler, and J. D. Groopman. 2007. Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry. Cancer Epidemiol Biomarkers Prev 16:1213-8.

Egner, P. A., Groopman, J. D., Wang, J. S., Kensler, T. W. & Friesen, M. D. (2006). Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometry. Chem Res Toxicol 19, 1191-5.

Egner, P.A., Kensler, T.W., Chen, J.G., Gange, S.J., Groopman, J.D., and Friesen, M.D. (2008). Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry. Chem Res Toxicol 21, 1991-1996.

Everley, R. A., F. L. Ciner, D. Zhan, P. F. Scholl, J. D. Groopman, and T. R. Croley. 2007. Measurement of aflatoxin and aflatoxin metabolites in urine by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 31:150-6.

Groopman, J. D. & Kensler, T. W. (2005). Role of metabolism and viruses in aflatoxin-induced liver cancer. Toxicol Appl Pharmacol 206, 131-7.

Groopman, J. D., Johnson, D. & Kensler, T. W. (2005). Aflatoxin and hepatitis B virus biomarkers: a paradigm for complex environmental exposures and cancer risk. Cancer Biomark 1, 5-14.

Groopman, J. D., T. W. Kensler, and C. P. Wild. 2007. Protective Interventions to Prevent Aflatoxin-Induced Carcinogenesis in Developing Countries. Annu Rev Public Health.

Groopman, J.D., and Kensler, T.W. (2008). Aflatoxin and Hepatitis B Virus: A Conspiracy in Human Liver Cancer. In: Molecular Epidemiology of Chronic Diseases, eds. C.P. Wild, P. Vineis, and S. Garte: Wiley, 323-342.

Groopman, J.D., and Wang, J., S,. (2008). Molecular Biomarkers. In: Comprehensive Toxicology, ed. C. McQueen: Pergamon Press, In Press.

Groopman, J.D., Kensler, T.W., and Wild, C.P. (2008). Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health 29, 187-203.

Johnson, D. N., P. A. Egner, G. O'Brien, N. Glassbrook, B. D. Roebuck, T. Sutter, G. A. Payne, T. W. Kensler, and J. D. Groopman. 2008. Quantification of Urinary Aflatoxin B1 Dialdehyde Metabolites Formed by Aflatoxin Aldehyde Reductase Using Isotope Dilution Tandem Mass Spectrometry. Chemical Research in Toxicology 21:752-760.

Johnson, D.N., Egner, P.A., Obrian, G., Glassbrook, N., Roebuck, B.D., Sutter, T.R., Payne, G.A., Kensler, T.W., and Groopman, J.D. (2008). Quantification of urinary aflatoxin B1 dialdehyde metabolites formed by aflatoxin aldehyde reductase using isotope dilution tandem mass spectrometry. Chem Res Toxicol 21, 752-760.

Kensler, T. W., Chen, J. G., Egner, P. A., Fahey, J. W., Jacobson, L. P., Stephenson, K. K., Ye, L., Coady, J. L., Wang, J. B., Wu, Y., Sun, Y., Zhang, Q. N., Zhang, B. C., Zhu, Y. R., Qian, G. S., Carmella, S. G., Hecht, S. S., Benning, L., Gange, S. J., Groopman, J. D. & Talalay, P. (2005). Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol Biomarkers Prev 14, 2605-13.

Kuang, S. Y., Lekawanvijit, S., Maneekarn, N., Thongsawat, S., Brodovicz, K., Nelson, K. & Groopman, J. D. (2005). Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand. Cancer Epidemiol Biomarkers Prev 14, 380-4.

Liby, K., Yore, M.M., Roebuck, B.D., Baumgartner, K.J., Honda, T., Sundararajan, C., Yoshizawa, H., Gribble, G.W., Williams, C.R., Risingsong, R., Royce, D.B., Dinkova-Kostova, A.T., Stephenson, K.K., Egner, P.A., Yates, M.S., Groopman, J.D., Kensler, T.W., and Sporn, M.B. (2008). A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin. Cancer Res 68, 6727-6733.

Links, J., and Groopman, J.D. (2008). Biomarkers of Exposure. In: Comprehensive Toxicology, ed. C. McQueen: Pergamon Press, In Press.

Lleonart, M. E., Kirk, G. D., Villar, S., Lesi, O. A., Dasgupta, A., Goedert, J. J., Mendy, M., Hollstein, M. C., Montesano, R., Groopman, J. D., Hainaut, P. & Friesen, M. D. (2005). Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry. Cancer Epidemiol Biomarkers Prev 14, 2956-62.

McCoy, L. F., Scholl, P. F., Schleicher, R. L., Groopman, J. D., Powers, C. D. & Pfeiffer, C. M. (2005). Analysis of aflatoxin B1-lysine adduct in serum using isotope-dilution liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 19, 2203-10.

McCoy, L.F., Scholl, P.F., Sutcliffe, A.E., Kieszak, S.M., Powers, C.D., Rogers, H.S., Gong, Y.Y., Groopman, J.D., Wild, C.P., and Schleicher, R.L. (2008). Human aflatoxin albumin adducts quantitatively compared by ELISA, HPLC with fluorescence detection, and HPLC with isotope dilution mass spectrometry. Cancer Epidemiol Biomarkers Prev 17, 1653-1657.

Roebuck, B.D., Johnson, D.N., Sutter, C.H., Egner, P.A., Scholl, P.F., Friesen, M.D., Baumgartner, K.J., Ware, N.M., Bodreddigari, S., Groopman, J.D., Kensler, T.W., and Sutter, T.R. (2009). Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat. Toxicol Sci.

Sapkota, A., Halden, R. U., Dominici, F., Groopman, J. D. & Buckley, T. J. (2006). Urinary biomarkers of 1,3-butadiene in environmental settings using liquid chromatography isotope dilution tandem mass spectrometry. Chem Biol Interact 160, 70-9.

Scholl, P. F., McCoy, L., Kensler, T. W. & Groopman, J. D. (2006). Quantitative analysis and chronic dosimetry of the aflatoxin B1 plasma albumin adduct Lys-AFB1 in rats by isotope dilution mass spectrometry. Chem Res Toxicol 19, 44-9.

Scholl, P. F., Turner, P. C., Sutcliffe, A. E., Sylla, A., Diallo, M. S., Friesen, M. D., Groopman, J. D. & Wild, C. P. (2006). Quantitative comparison of aflatoxin B1 serum albumin adducts in humans by isotope dilution mass spectrometry and ELISA. Cancer Epidemiol Biomarkers Prev 15, 823-6.

Scholl, P.F., and Groopman, J.D. (2008). Long-term stability of human aflatoxin B1 albumin adducts assessed by isotope dilution mass spectrometry and high-performance liquid chromatography-fluorescence. Cancer Epidemiol Biomarkers Prev 17, 1436-1439.

Simonich, M. T., P. A. Egner, B. D. Roebuck, G. A. Orner, C. Jubert, C. Pereira, J. D. Groopman, T. W. Kensler, R. H. Dashwood, D. E. Williams, and G. S. Bailey. 2007. Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat. Carcinogenesis 28:1294-302.

Skipper, P. L., Trudel, L. J., Kensler, T. W., Groopman, J. D., Egner, P. A., Liberman, R. G., Wogan, G. N. & Tannenbaum, S. R. (2006). DNA adduct formation by 2,6-dimethyl-, 3,5-dimethyl-, and 3-ethylaniline in vivo in mice. Chem Res Toxicol 19, 1086-90.

Turner, P. C., Sylla, A., Kuang, S. Y., Marchant, C. L., Diallo, M. S., Hall, A. J., Groopman, J. D. & Wild, C. P. (2005). Absence of TP53 codon 249 mutations in young Guinean children with high aflatoxin exposure. Cancer Epidemiol Biomarkers Prev 14, 2053-5.

Wang, J., S,, and Groopman, J.D. (2008). Physical/Chemical/Immunologic Analytical Methods. In: Molecular Epidemiology and Biomarkers: IARC Press.

Yates, M. S., Kwak, M. K., Egner, P. A., Groopman, J. D., Bodreddigari, S., Sutter, T. R., Baumgartner, K. J., Roebuck, B. D., Liby, K. T., Yore, M. M., Honda, T., Gribble, G. W., Sporn, M. B. & Kensler, T. W. (2006). Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole. Cancer Res 66, 2488-94.

Yuan, J.M., Ambinder, A., Fan, Y.H., Gao, Y.T., Yu, M.C., and Groopman, J.D. Prospective Evaluation of Hepatitis B 1762T/1764^ Mutations on Hepatocellular Carcinoma Development in Shanghai, China. Cancer Epidemiol Biomarkers Prev 18, 590-594.

Egner, P. A., Yu, X., Johnson, J. K., Nathasingh, C. K., Groopman, J. D., Kensler, T. W., et al. 2003. Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1. Chem. Res. Toxicol. 16:1174-1180.

Jackson, P. E., Kuang, S. Y., Wang, J. B., Strickland, P. T., Munoz, A., Kensler, T. W., et al. 2003. Prospective detection of codon 249 mutations in p53 in plasma of hepatocellular carcinoma patients. Carcinogenesis. 10:1657-1663.

Kuang, S. Y., Jackson, P. E, Wang, J. B., Lu, P. X., Munoz, A., Qian, G. S., et al. 2004. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc. Natl. Acad. Sci. USA. 101:3575-3580.

Kuang, S. Y., Lewanvijit, S., Maneekarn, N., Thongsawat, S., Brodovicz, K., Nelson, K., et al. 2005. Hepatitis B 1762T/1764A virus mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand. Cancer Epidem. Biomar. 14:380-384.

O'Gorman, M., Sharma, S., Groopman, J. D., Tennant, B., Tochkov, I., & Schwarz, K. B. 2003. Decreased oxidative DNA damage and accelerated cell turnover in woodchuck hepatitis virus infected liver. Hepatol. Res. 25:254-262.

 

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