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Isaac WirginAssociate Professor, Department of Environmental Medicine
57 Old Forge Rd.
Tuxedo, NY 10987
The Atlantic tomcod, Microgadus tomcod, from the Hudson River provides a unique opportunity to study the molecular aspects of genetic susceptibility to neoplasia in an outbred model organism that 1) exhibits an unusually high prevalence of hepatocellular carcinomas (more than 90% in 2-yr-old fish), 2) is exposed to high levels of environmentally borne chemical carcinogens, and 3) can be used to investigate the effects of controlled laboratory model-chemical exposures on sensitive early-life stages.
We examined the effects of the interactions of genetic variation and exposure to high levels of Hudson River-borne xenobiotics on the structure and expression of carcinogenically relevant genes, such as K-ras, aromatic hydrocarbonreceptor (Ahr) and cytochrome P4501A (CYP1A1). We found activated K-ras in a high percentage of tomcod liver-tumor DNAs, a transcribed genetic polymorphism in the 3' untranslated region of CYP1A1 in Hudson River tomcod that is not observed in cancer-free populations of tomcod.
Currently, we study the functional significance of genetic variation in this model relevant to: 1) the role of K-ras oncogene activation in early neoplastic events and hepatocarcinogenesis progression in tomcod livers, 2) the effects of environmentally relevant polychlorobiphenyl (PCB) promotion on clonal expansion of initiated cells, and 3) the molecular mechanisms of CYP1A1 gene regulation in environmentally exposed tomcod from the Hudson River. We also explore the effects of inter-specific and inter-individual differences in Ahr gene expression levels on CYP1A1 gene expression and transcription inhibition in halogenated aromatic hydrocarbon-exposed fish.
Research InterestsMolecular Mechanisms of Carcinogenesis in Hudson River Tomcod
Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology
Clendenen, Tess V; Rendleman, Justin; Ge, Wenzhen; Koenig, Karen L; Wirgin, Isaac; Currie, Diane; Shore, Roy E; Kirchhoff, Tomas; Zeleniuch-Jacquotte, Anne
2015-08-17; 1932-6203,PLoS one - id: 1721892, year: 2015 JOURNAL ARTICLE
Population origin of Atlantic sturgeon Acipenser oxyrinchus oxyrinchus by-catch in U.S. Atlantic coast fisheries
Wirgin, I; Maceda, L; Grunwald, C; King, T L
2015-05-08; 1095-8649,Journal of fish biology - id: 1565632, year: 2015 Journal Article
Origin of Atlantic Sturgeon Collected off the Delaware Coast during Spring Months
Wirgin, Isaac; Breece, Matthew W.; Fox, Dewayne A.; Maceda, Lorraine; Wark, Kevin W.; King, Tim
2015-05-04; 0275-5947,North American journal of fisheries management - id: 1559972, year: 2015
Genetic Mixed-Stock Analysis of American Shad in Two Atlantic Coast Fisheries: Delaware Bay, USA, and Inner Bay of Fundy, Canada
Waldman, John; Hasselman, Daniel; Bentzen, Paul; Dadswell, Michael; Maceda, Lorraine; Wirgin, Isaac
2015-02-19; 1548-8675,North American journal of fisheries management - id: 1464742, year: 2014
Coastwide Stock Structure of Winter Flounder Using Nuclear DNA Analyses
Wirgin, Isaac; Maceda, Lorraine; Grunwald, Cheryl; Roy, Nirmal K.; Waldman, John R.
2014-02-19; 0002-8487,Transactions of the American Fisheries Society - id: 807952, year: 2014