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Transgenic Carcinogenesis Group

Causes of Cancer

Not pictured
John E. (Jef) French, Ph.D.
Principal Investigator

Tel (919) 541-2569
Fax (919) 541-1460

P.O. Box 12233
Mail Drop F1-05
Research Triangle Park, North Carolina 27709
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Research Summary

The Transgenic Carcinogenesis Group uses a variety of research strategies and approaches to identify the causal genetic interactions and an environmental exposure DNA damage and repair that result in cancer. Cancer has a complex etiology, including genome-environment interaction basis. By using isogenic strains of mice and recombinant inbred strains that isolate genes in their different forms (allelic variants) to identify DNA repair phenotypes, in vitro human and mouse cell hematopoietic stem cells in primary culture can be compared, and the genes and their alleles involved in the susceptibility to an environmental exposure and cancer can be identified. By quantifying exposure and determining the prevalence of the disease and using quantitative genetic (statistical) and complex trait analysis, the group will identify the genetic basis for an environmental exposure of a carcinogen (e.g. ionizing radiation) and the induction of a neoplasia in an animal model (e.g. a mouse) with features in common with a similar human disease. If the mechanistic basis shown in the mouse model is consistent with known human mechanisms of DNA damage and repair, this allows experimental studies in mouse models that can be used for extrapolation to human health effects. This approach may help to minimize the uncertainty of extrapolation between rodents and humans for risk estimation, while still providing valuable mechanistic information on the cause of the disease that can be used to develop policies and strategies for prevention and clinical intervention and treatment.

The advancement of the stated aims will enhance scientific understanding of the genetic basis for individual differences in the tissue-specific dysregulation of apoptosis and signaling pathways involved in the repair of carcinogen-induced DNA damage leading to genomic instability and aneuploidy, the hallmarks of neoplasia.

Major areas of research:

  • Gene-environment interaction in mouse models for genetic susceptibility to carcinogen induced DNA damage, repair, and cancer
  • Genetic susceptibility and mechanism of the loss of tumor suppressor gene function in genetically-engineered mouse models for environmental carcinogenesis
  • Pleiotropic role of Bcl2 expression in apoptosis, cell adhesion, spreading and motility and cancer stem cells

Current projects:

  • Quantification of ionizing radiation induced DNA strand break and repair in mouse and human hematopoietic stem cells in long term culture
  • Bioinformatic and haplotype analysis of DNA strand break repair genes in 16 sequenced isogenic stains of mice
  • Bcl2 and gelsolin interactions in cell adhesion, spreading and motility

John E. (Jef) French, Ph.D., heads the Transgenic Carcinogenesis Group within the Laboratory of Molecular Toxicology. He received his Ph.D. in molecular toxicology and comparative biochemistry from North Carolina State University in 1975. He has published more than 100 peer-reviewed articles in leading biomedical journals and NTP technical reports, as well as several book chapters. He served as Supervisory Research Physiologist at the FDA Center for Biologics Evaluation and Research before joining NIEHS in 1982.

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Last Reviewed: December 31, 2008