Jay I. Goodman
Professor, Pharmacology and Toxicology
1355 BOGUE ST ROOM B423B
EAST LANSING MI 48824
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.
Long Island University, College of Pharmacy, B.S., 1965
University of Michigan, Ph.D., pharmacology, 1969
Selected Professional Activities:
Dr. Goodman completed postdoctoral training at the University of Wisconsin. He has received the Distinguished Alumnus Award, Long Island University, College of Pharmacy, 1998; was Elected President of the Society of Toxicology, 1999-2000; the Distinguished Alumnus Award, Doctoral Program in Pharmacology, The University of Michigan, 2000; gave the John Barnes Prize Lecture, British Toxicology Society in 2005; and is the recipient of the Society of Toxicology's Merit Award, 2014. Dr. Goodman is a faculty trainer for the NIEHS training grant.
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