Jay Goodman, Ph.D.
- D-G, Environmental Faculty, Hepatic Faculty, Online Faculty
Pharmacology & Toxicology
Dr. Jay Goodman
310 Food Safety and Toxicology
1129 Farm Lane
East Lansing, MI 48824
Fields of Interest: My research interests are focused on discerning epigenetic mechanisms underlying carcinogenesis and other chemical-induced toxicities.
- 1965 - B.S., Brooklyn College of Pharmacy
- 1969 - Ph.D., Pharmacology, The University of Michigan
- 1969-1971 - McArdle Laboratory for Cancer Research, University of Wisconsin
- 1971-1975 - Assistant Professor, Pharmacology, Michigan State University
- 1975-1982 - Associate Professor, Pharmacology & Toxicology, Michigan State University
- 1982-present - Professor, Pharmacology & Toxicology, Michigan State University
- 2001-2002 - Interim Chairperson, Pharmacology & Toxicology, Michigan State University
Toxicology: A Personal Perspective
My research interests are focused upon discerning mechanisms underlying the ability of chemicals to cause adverse effects. What excites me about research in toxicology is that it combines the theoretical with the practical. While pursuing research aimed at understanding the mechanism(s) of action of the chemical of interest, we learn more about fundamen-tal aspects of biology. Thus, toxicology is a basic biomedical science. On the practical side, the new knowledge gleaned facilitates the enhancement of science-based safety assessment of chemicals. This permits a rational approach towards resolving key issues, e.g., dose-response relationships and appropriate extrapolation from test species to humans. Thus, toxicological research plays a key role by facilitating our ability to safely use chemicals (including, but not limited to, medi-cines, consumer products and agricultural chemicals) to enhance the quality of people's lives. Therefore, I view toxicology as "part of the solution." This is a theme that I began advocating when I was President of the Society of Toxicology (1999-2000)
The involvement of mutagenesis in carcinogenesis needs to be reconciled with the fact that not all carcinogens are mutagens and the view that nonmutagenic events also play key roles in the transformation of a normal cell into a cancer cell. This apparent paradox can, in part, be resolved by considering the roles that altered DNA methylation, an epigenetic mechanism, play in carcinogenesis.
Gene expression is not determined only by DNA base sequence; it also depends on epigenetic mechanisms, i.e., heritable gene-regulating mechanisms not involving a change in DNA base sequence. Inheritance occurs on two levels. The transmission of genes either in the somatic sense or from generation to generation is distinct from mechanisms involved in transmission of alternative states of gene activity.
Epigenetics describes the latter and involves regulation of temporal and spatial control of gene activity, e.g., changes in gene expression during development, imprinting, segregation of gene activities such that daughters of a cell exhibit different patterns of gene expression, and mechanisms that permit the somatic inheritance of a specific set of active and quiescent genes.
DNA methylation (the presence of 5-methylcytosine (5MeC) as compared to cytosine) is an epigenetic mechanism controlling gene activity. Changes in DNA methylation are not mutations because 5MeC and cytosine base pair with guanine. In general, increased methylation of a gene is associated with deceased transcription (e.g., may silence tumor suppressor genes, functionally equivalent to inactivation due to point mutation or allelic loss) and decreased methylation may up-regulate gene expression (e.g., may increase expression of oncogenes). Thus, altered DNA methylation can facilitate the aberrant gene expression underlying carcinogenesis.
The hypothesis being tested in my laboratory is that susceptibility to carcinogenesis, and perhaps other toxicities, is related inversely to the capacity to maintain normal patterns of DNA methylation. Particular emphasis is being placed on discerning novel genes that are involved in carcinogenesis due to aberrant methylation.
- Recipient of the Pharmaceutical Research and Manufacturers of America (PhRMA) Award in Excellence in Pharmacology/Toxicology, 2019
- Recipient of the International Society of Regulatory Toxicology and Pharmacology's International Achievement Award, 2014
- Recipient of the Society of Toxicology's Merit Award, 2014
- Plenary Lecture, Annual Meeting of the European Societies of Toxicology (EUROTOX), 2009
- Recipient of the George H. Scott Memorial Award, awarded by the Toxicology Forum, 2007
- Invited speaker, Annual John Doull Symposium, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas, 2007
- Recipient of the John Barnes Prize Lecture, awarded by the British Toxicology Society, 2005
- Distinguished Alumnus Award, Doctoral Program in Pharmacology, The University of Michigan, 2005
- President, Society of Toxicology 1999-2000
- Distinguished Alumnus Award, Long Island University College of Pharmacy, 1998
- Toxicological Sciences, 1997-2007
- Regulatory Pharmacology and Toxicology, 1999-2018
- Toxicology, 2018
Editorial Board Membership
- Toxicology, 2008-present
Membership on Advisory Committees
- Member of the Committee to Evaluate the IRIS (US Environmental Protection Agency's Integrated Risk Information System) Protocol for Inorganic Arsenic, National Academies of Science, National Research Council, Board on Environmental Studies and Toxicology, 2018-2019
- Member of the Board of Trustees, The Toxicology Forum, 2015-2018
- Member, Board of Scientific Counselors, NIH, NIEHS, 2008-2013
- Member, Advisory Committee to the Director, Center for Disease Control and Prevention, Atlanta, GA, 2005-2008
- Member, International Scientific Program Planning Committee, International Congress of Toxicology (ICT XI), Montreal, Canada, 2005-2007
- Participant, Strategic Implementation Leadership Committee Meeting, American Chemistry Council, Chlorine Chemistry Council, 2004
- Member of Council, Academy of Toxicological Sciences, 2002-2005
- Chairperson, Executive Committee, International Life Sciences Institute, Health and Environmental Sciences Institute, 2002-2004; currently, member of the Board of Trustees and member of the Executive Committee
- Member, Global Environmental Advisory Council, Dow AgroSciences, 2000-2004
- Member, Alumni Steering Committee, Department of Pharmacology, The University of Michigan, 2001-present
- Member of Council, International Society of Regulatory Toxicology and Pharmacology, 2001-2008
- Member, Nonclinical Studies Subcommittee of the Advisory Committee for Pharmaceutical
- Sciences, U.S. Food and Drug Administration, 1999-2002
- Member, Board of Scientific Counselors, National Toxicology Program, 1989-1992
Society of Toxicology
- President, 1999-2000
- Member, Task Force to Improve the Scientific Basis for Risk Assessment, 1996-1999
- Chairperson, Steering Committee of the Mixtures Project, 2001-2003
- Member, Awards Committee, 2009-2012
- Member of the Nominating Committee, 2017-2018
Presentations at National & International Meetings
- Invited speaker, "Epigenetics: Implications for safety assessment." Symposium entitled "Epigenetic mechanisms as Drug Targets: Toxicological Considerations," annual meeting of the American College of Toxicology, Palm Springs, CA, November 2017.
- Invited participant, Toxicoepigenetics meeting, a Society of Toxicology Current Concepts in Toxicology meeting, Tysons, VA, November 2016.
- Invited participant, Toxicology Forum, Relevance of Rodent Liver Tumours workshop, Arlington, VA, October 2016.
- "Toxicity testing in the 21st century: Making progress by maintaining a focus on the fundamentals. Annual Summer meeting of The Toxicology Forum, Colorado Springs, CO, July 2015
- "Regulation of chemicals based on an epigenetic liability: Are we there yet?." Symposium entitled "Environmental epigenetics, epigenotoxic assays and regulation." Environmental Mutagenesis and Genomics Society, Orlando, FL, September 2014
- "Driving CAR (Constitutive Androstane Receptor) to Carcinogenesis: Mechanistic and Practical Implications," Symposium entitled, "Receptors at the Interplay Between Endogenous and Xenobiotic Agonists." Annual Congress of the European Societies of Toxicology (EUROTOX) Edinburgh, Scotland, September 2014.
- "A Systems Biology Approach to Epigenetics: Implications for Safety Assessment," Janssen Pharmaceuticals, Inc., Johnson & Johnson Research and Development. Raritan, NJ, August 2014.
- "A Systems Biology View of Epigenetics: Implications for Safety Assessment," Symposium entitled "Epigenetic Endpoints in Toxicologic Pathology and Relevance to Human Health," Society of Toxicologic Pathology Annual Symposium. Washington, D.C., June 2014.
- An Integrated View of Epigenetics: Implications for Safety Assessment, Gordon Research Conference, Mechanisms of Toxicity Andover, NH, August 2013.
- Adverse v. Adaptive: A View from the Epigenetic Landscape, Session on Adverse Versus Adaptive Effects in Toxicology Studies: Application to Human Risk Assessment," Annual Summer Meeting of the Toxicology Forum, Aspen, CO, July 2013.
- Driving CAR to Rodent Liver Tumors: Altered DNA Methylation, Gene expression and Implications for Safety Assessment." 20thEUROTOX Training and Discussion Session, Epigenetic Carcinogenicity in Risk Assessment, Dortmund, Germany, February 2013.
- Identification of Genes Involved in Phenobarbital-Induced Mouse Liver Carcinogenesis: Emphasis on Altered DNA Methylation, Expression and Pathways," workshop entitled "Human Relevance of Rodent Hepatocarcinogenicity," BASAF, Bad Durkheim, Germany, November 2012.
Full list of publications at MSU Scholars
- Alterations in DNA methylation may play a variety of roles in carcinogenesis. Counts JL, Goodman JI. Cell. 1995 Oct 6;83(1):13-5. Review. No abstract available. PMID: 7553865 [PubMed - indexed for MEDLINE]
- The constitutive active/androstane receptor facilitates unique phenobarbital-induced expression changes of genes involved in key pathways in precancerous liver and liver tumors. Phillips JM, Burgoon LD, Goodman JI. Toxicol Sci. 2009 Aug;110(2):319-33. doi: 10.1093/toxsci/kfp108. Epub 2009 May 29. PMID: 19482888 [PubMed - indexed for MEDLINE] Free PMC Article
- Changes in DNA methylation and gene expression during 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced suppression of the lipopolysaccharide-stimulated IgM response in splenocytes. McClure EA, North CM, Kaminski NE, Goodman JI. Toxicol Sci. 2011 Apr;120(2):339-48. doi: 10.1093/toxsci/kfq396. Epub 2011 Jan 6. PMID: 21212295 [PubMed - indexed for MEDLINE] Free PMC Article
- Identification of Dlk1-Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion. Lempiäinen H, Couttet P, Bolognani F, Müller A, Dubost V, Luisier R, Del Rio Espinola A, Vitry V, Unterberger EB, Thomson JP, Treindl F, Metzger U, Wrzodek C, Hahne F, Zollinger T, Brasa S, Kalteis M, Marcellin M, Giudicelli F, Braeuning A, Morawiec L, Zamurovic N, Längle U, Scheer N, Schübeler D, Goodman J, Chibout SD, Marlowe J, Theil D, Heard DJ, Grenet O, Zell A, Templin MF, Meehan RR, Wolf RC, Elcombe CR, Schwarz M, Moulin P, Terranova R, Moggs JG. Toxicol Sci. 2013 Feb;131(2):375-86. doi: 10.1093/toxsci/kfs303. Epub 2012 Oct 22. PMID: 23091169 [PubMed - indexed for MEDLINE]
- Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: A case study with phenobarbital as a model constitutive androstane receptor (CAR) activator. Elcombe CR, Peffer RC, Wolf DC, Bailey J, Bars R, Bell D, Cattley RC, Ferguson SS, Geter D, Goetz A, Goodman JI, Hester S, Jacobs A, Omiecinski CJ, Schoeny R, Xie W, Lake BG. Crit Rev Toxicol. 2014 Jan;44(1):64-82. doi: 10.3109/10408444.2013.835786. Epub 2013 Nov 4. PMID: 24180433 [PubMed - in process]
- Elcombe, C.R., Peffer, R., Wolf, D.C., Bailey, J., Bars, R., Cattley, R., Ferguson, S., Geter, D., Goetz, A., Goodman, J., Hester, S., Jacobs, A., Omiecinski, C., Schoeny, R., Xie, W. and Lake, B.: Mode of Action and Human Relevance Analysis for Nuclear Receptor-Mediated Toxicity: A Case Study with Phenobarbital as a Model Constitutive Androstane Receptor (CAR) Activator. Critical Reviews in Toxicology, 44: 64-82, 2014.
- Luisier, R., Unterberger, E.B., Goodman, J.I., Schwarz, M., Moggs, J. Terranova, R., and Van Nimwegen, E.: Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion. Nucleic Acids Res., 2014, 1-16, doi: 10.1093/nar/gkt1415
- Currie, R.A., Peffer, R.C., Goetz, A.K., Omiecinski, C.J. and Goodman, J.I.: Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistyent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action. Toxicology 321: 80-88, 2014.
- Wolf, D.C., Bachman, A., Barrett, G., Bellin, C., Goodman, J.I., Jensen, E., McMullin, T., Pastoor, T.P., Schoney, R., Slezak, B., Wend, K. and Embry, M.R.: Illustrative Case Using the RISK21 Roadmap and Matrix: Prioritization for Evaluation of Chemicals Found in Drinking Water. Critical Reviews in Toxicology, 46: 43-53, 2016.
- Boobis, A.R., Brown, P., Mark Cronin, M., Edwards, J., Galli, J.C., Goodman, J., Jacobs, A., Kirkland, D., Luijten, M., Marsaux, C. F.M., Martin, M., Yang, C., and Hollnagel, H.M. Origin of the TTC (Threshold of Toxicologic Concern) values for compounds that are genotoxic and/or carcinogenic and an approach for their revaluation. Critical Reviews in Toxicology, 47: 710-732, 2017. doi: 10.1080/10408444.2017.1318822. PMID: 28510487
- Goodman, JI. Incorporation of an epigenetic evaluation into safety assessment: What we first need to know. Current Opinions in Toxicology 3: 20-24, 2017.
- Felter, S.P., Foreman, J.E., Boobis, A., Corton, J.C., Doi, A.M., Flowers, L., Goodman, J., Haber, L.T., Jacobs, A., Klaunig, J.E., Lynch, A.M., Moggs, J., Pandiri, A. (2018). Human relevance of rodent liver tumors: Key insights from a Toxicology Forum workshop on nongenotoxic modes of action. Reg. Toxicol. Pharmacol. 92: 1-7. doi: 10.1016/j,yrtph.2017.11.003. PMID: 29113941
- Goodman, JI. Goodbye Bioassay. Toxicology Research, 7: 558-564, 2018. doi: 10.1039/c8tx90016q. PMID: 30310677