Principal Investigator/Program Director (Last, First, Middle) Trosko, James E. BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE James E. Trosko Professor eRA COMMONS USER NAME EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Central Michigan University, Mt. Pleasant, MI Michigan State University, East Lansing, MI Michigan State University, East Lansing, MI Oak Ridge National Lab, Oak Ridge, TN DEGREE (if applicable) YEAR(s) B.A. M.S. Ph.D. Post-Doc 1960 1962 1963 1963-66 FIELD OF STUDY Chemistry, Biology Genetics Radiation Genetics Molecular Genetics PROFESSIONAL EXPERIENCE: 1963-1965 Postdoctoral Fellow, Oak Ridge National Laboratory, Oak Ridge, TN, with Dr. E. Chu, Dr. S. Wolff and Dr. B.B. Setlow. 1965-1966 Staff Research Biologist, Oak Ridge National Laboratory, Oak Ridge, TN. Assistant Professor, Dept. of Natural Science, Michigan State University, East Lansing, MI. 1970-Summer Visiting Scientist, Biology Division, Oak Ridge National Laboratory with Dr. E. Chu and Dr. R.B. Setlow. 1971-Summer Trainee, Summer Workshop in Molecular Biology, University of California, La Jolla, CA. 1972-1973 Visiting Professor of Oncology, University of Wisconsin, McArdle Laboratory for Cancer Research in Dr. Van R. Potter's laboratory, Madison, WI. 1972-1973 NCI Research Career Development Awardee. 1971-1976 Associate Professor, Dept. of Human Development, Michigan State University, East Lansing, MI. 1975-Spring Research leave of absence to the Ohio State Cancer Center, working with Dr. R.W. Hart. 1990-1992 Chief of Research, Radiation Effects Research Foundation, Hiroshima, Japan. 2006 Korean Ministry of Science & Technology “Brain Pool” Visiting Professor in Human Adult Stem Cell Research at Seoul National University 1976-present Professor, Dept. of Pediatrics/Human Development, Michigan State University, East Lansing, MI. HONORS: Summa Cum Laude, CMU, 1956; Argonne Nat'l. Lab., Summer Participant, 1958-1959; NDEA Predoctoral Fellow, 1960-1963; Oak Ridge Nat'l Lab., Postdoctoral Fellow, 1963-1964; American Cancer Society, Postdoctoral Fellow, 1965-1966; Teacher-Scholar Award, Michigan State University, 1970; NCIResearch Career Development Award, 1972-1977; Searle Award from U.K. Environmental Mutagen Society, 1990; Sigma Xi Senior Scientist Award, 1985; Distinguished Faculty Award, Michigan State University, 1987; Kenneth B. DuBois Award–Midwest SOT, 1995; Scientific Achievement Award, Society of Toxicology, 2000, Korean Ministry of Science & Technology “Brain Pool Award”-2006; PUBLICATIONS: (Selected from 403 Publications) Yotti, L.P., C.C. Chang, J.E. Trosko: Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science 206: 1089-1091, 1979. El-Fouly, M.H., J.E. Trosko and C.C. Chang: Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication. Mol. Carcinogenesis 2:131-135, 1989. de Feijter, A.W., J.S. Ray, C.M. Weghorst, J.E. Klaunig, J.I. Goodman, C.C. Chang, R.J. Ruch and J.E. Trosko: Infection of rat liver epithelial cells with v-Ha-ras: Correlation between oncogene expression, gap junctional communication, and tumorigenicity. Mol. Carcinogenesis 3:54-67, 1990.. PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page Principal Investigator/Program Director (Last, First, Middle) Trosko, James E. Ruch, R.J., B.V. Madhukar, J.E. Trosko and J.E. Klaunig: Reversal of ras-induced inhibition of gap junction intercellular communication, transformation and tumorigenesis by lovastatin. Molec. Carcinogenesis 7:50-59, 1993. Matesic, D.F., H.L. Rupp, W.J. Bonney, R.J. Ruch, and J.E. Trosko: Changes in gap junction permeability, phosphorylation, and number mediated by phorbol ester and non-phorbol ester tumor promoters in rat liver epithelial cells. Molec. Carcinogenesis 10:226-236, 1994. Upham, B.L., K.-S. Kang, H.-Y. Cho, and J.E. Trosko: Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells. Carcinogenesis 18:37-42, 1997. Rae, R.S., P.P. Mehta, C.C. Chang, J.E. Trosko, and R.J. Ruch: Neoplastic phenotype of gap-junctional intercellular communication-deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32. Molecular Carcinogenesis 22:120-127, 1998. Wilson, M.R. Close, T.W., and Trosko, J.E.: Cell population dynamics (apoptosis, mitosis, and cell-cell communication) during disruption of homeostasis. Exp. Cell Res. 254:257-268, 2000. DeoCampo, N.D., M.R. Wilson and J.E. Trosko: Cooperation of Bcl-2 and Myc in the neoplastic transformation of normal rat liver epithelial cells is related to the down regulation of gap junction-mediated intercellular communication. Carcinogenesis 21: 1501-1506, 2000. Sai, K., Kanno, J., Hasegawa, R., Trosko, J.E. and Inoue, T.: Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol. Carcinogenesis 21: 1671-1676, 2000. Trosko, J.E. and Ruch, R. J. “Gap junctions as therapeutic targets”, Current Drug Targets 3: 465-482, 2002. Tai, M.H., Olson, K., Madhukar, B.V., Linning, K.D., Van Camp, L., Tsao, M.S., and Trosko, J.E.: “Characterization of gap junctional intercellular communication in immortalized human pancreatic ductal epithelial cells with stem cell characteristics”. Pancreas 26: e18- 26, 2003. Moggs, J.G., Goodman, J.I., Trosko, J.E., Roberts, R.A.: Epigenetics and cancer: implications for drug discovery and safety assessment”. Tox. Appl. Pharmacol., 196: 422-430, 2004. Tai, M.H., Chang, C.C., Kiupel, M., Webster, J.D., Olson, L.K. and Trosko, J.E.: “ Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26: 495-502, 2005. Nakamura, Y., Chang, C.C., Mori,T., Sato, K., Ohtsuki, K., Upham, B.L., and Trosko, J.E.: “ Augmentation of differentiation and gap junction by kaempferol inpartially-differentiation colon cancer cells. Carcinogenesis, 26: 665-671, 2005. Trosko, J.E. “The role of stem cells and cell-cell communication in radiation carcinogenesis: ignored concepts”. Brit. J. Radiol., 78: 1-7, 2005. Trosko, J.E. and Upham, B.L. “The emperor wears no clothes in the field of carcinogen risk assessment: Ignored concepts in cancer risk assessment”. Mutagenesis 20: 81-92, 2005. Trosko, J.E., Chang, C.C., Upham, B.L., and Tai, M.H., “The role of human adult stem cells and cell-cell communication in cancer chemoprevention and chemotherapy strategies”. Mutat. Res., 591: 187-197, 2005. Tai, M.H., Chang, C.C., kiupel, M., Webster, J.D., Olson, L.K. and Trosko, J.E., “Oct-4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26: 495-502, 2005. Trosko, J.E. and Upham, B.L. “The emperor wears no clothes in the field of carcinogen risk assessment: Ignored concepts in cancer risk assessment”. Mutagenesis 20: 81-92, 2005. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle) Trosko, James E. Trosko, J.E. and Ruch, R.J. “Gap junctional Intercellular Communication in Epigenetic Toxicology” In: Encyclopedia of Toxicology, 2nd Ed., P. Wexler, ed., Elsevier Press, Oxford, pp. 402- 407, 2005. .Ogawa, T., Hayashi, T., Tokunou, M., Nakachi, K., Trosko, J.E., Chang, C.C., and Yorioka, N., “Suberoylanilide hydroxamic acid enhances gap junctional intercellular communication via acetylation of histone containing connexin43 gene locus”. Cancer Res. 65: 9771-9778, 2005. de Flora, S., Scafi, S., Izzotti, A., D’Agostini, F., Chang, C.C., Bagnasco, M., De Flora, A., and Trosko, J.E., “ Induction by 7, 12-dimethylbenz(a) anthracene of molecular and biochemical alterations in stem cell-derived human mammary epithelial cells, and protection by N-acetylcysteine”. Internatl. J. Oncology, 29:521-529, 2006. Trosko, J.E. From adult stem cells to cancer stem cells: Oct-4 gene, Cell-Cell Communication, and Hormones during tumor promotion. Ann. N.Y. Acad. Sci., 1089: 36-58, 2006. Tai, M.H., Upham, B.L., Olson, L.K., Tsao, M.S., Reed, D.N., and Trosko, J.E., “Cigarette smoke condensate inhibited intercellular communication and differentiation in human pancreatic ductal epithelial cells”.Int. J. Cancer 120: 1855-1862, 2007. Upham,B.L., Guzvic, M., Scott, J., Carbone, J.M., Blaha, L., Coe, C., Li, L.L., Rummel, A.L. and J.E. Trosko, “ Inhibition of gap junctional intercellular communication and activation of mitogen-activation protein kinase by tumor-promoting organic peroxides and protection by resveratrol”. Nutrition Cancer 57: 38-47, 2007 Trosko , J.E., “ Gap junction intercellular communication as a ‘Biological Rosetta Stone’ in understanding , in a Systems manner, stem cell behavior, mechanisms of epigenetic toxicology, chemopreventyion and chemotherapy”. J. Membr. Biol.218: 93-100, 2007 Trosko, J.E., “Stem cells and cell-cell communication in the understanding of the role Of diet and nutriets in human diseases. J. Food Hygiene & Safety 22: 1-14, 2007. Webster, J.D., Yuzbasiyan-Gurkan, V., Trosko, J.E., Chang, C.C., and Kiupel, M, “Expression of the embryonic transcription factor Oct4 in canine neoplasms: A potential marker for stem cell subpopulations in neoplasis. Vet. Pathol., 44: 893-900, 2007. Upham, B.; Blaha, L.; Babica, P.; Park.; Sovadinova, I.; Pudrith, C.; Rummel, A.; Weis, L.; Sai, K.; Tithof, P.; Guzvic, Miodrag; V., J.; Machala, M.; Trosko, J., “Inhibition of intercellular signaling, a tumor promotion event, by a cigarette abundant PAH, depends on phosphatidylcholine-specific phospholipase C. Cancer Sci., 99: 696-705, 2008. Upham, B.L. and Trosko, J.E., “Carcinogenic tumor promotion, induced oxidative stress signaling, modulated gap junction function and altered gene expression”. Antioxidants & Redox Signaling, in press. Nakamura, Y, Nakayama, Y., Ando, H., Tanaka, A., Matsuo, T., Okamoto, S., Upham, B.L., Chang, C.C., Trosko, J.E., Park, E. Y., Sato, K. “3-Methylthio-propionic acid ethyl ester, isolated from Katsura-uri (Japanes pickling melon, Cucumis melo var. conomon), enhanced differentiation in human colon can cells”, J. Agriculture and Food Chem.. 56, 2977–2984, 2008 Trosko, J.E. “Commentary: Re-Programming or Selecting adult stem cells. Stem Cell Reviews, 4: 81-88, 2008. A. Research Support. ACTIVE PHS 398/2590 (Rev. 09/04) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle) Trosko, James E. 1. R01 (B.L. Upham, P.I.; J.E. Trosko, CoInvestigator) 8/15/2008– 8/15/2009 35% $1,075,875 NIEHS R01 ES013268-01A2 Epigenetic toxicity of polycyclic aromatic hydrocarbons. The major goals of this project are to determine the signal transduction pathways involved in polycyclic aromatic hydrocarbon-induced changes on gap junctional intercellular communication and mitogen activated protein kinases in rodent stem cell development. Role: Co-Investigator. 2. MSU-IRGP Grant . J.E. Trosko, P.I. 01/01/09- 12/31/209 MSU-IRGP “Developing Mannitou glycan as a clinical biomarker for the early detection of cancer: Search for the possible co-expression with a ‘cancer stem cell marker’, Oct-4”. PENDING: PHS 398/2590 (Rev. 09/04) Page Continuation Format Page