User:John E. French

John E. French, Ph.D., is a research scientist and Group Leader, Host Susceptibility Branch at the NTP/NIEHS in Research Triangle Park, North Carolina. His primary goal is develop new laboratory-based models and testing protocols for hazard identification and risk assessment. These models and protocols are based upon the quantitative differences in the variable range of responses that correlate with individual susceptibility to toxicity and disease. Individual genetic differences harbored within the human population are believed to be the basis for individual susceptibility to environmental stressors, including idiosyncratic drug toxicities. At present environmental and drug safety assessment models use a very limited set of genetic models, which are insufficient to evaluate the influence of individual genetic differences on chemical and drug toxicity. The aim of this research and testing program is to model the significant genetic diversity in the human population using genetically diverse laboratory animals. To meet this aim, the HSB is:planning, conducting and analyzing research on chemical toxicity using multiple genetically-defined and/or genetically-modified animal models and developing the research base for internal and external research collaborations to promote investigation of the genetic basis for individual differences in susceptibility. By identifying the quantitative trait loci by haplotype-phenotype segregation analysis and conducting functional validation of the candidate genes to identify their allelic variants — that modify individual response to chemical exposure and disease — the HSB can identify the key genes and pathways involved in response to chemical exposures of presumed or known risk to humans. Using bioinformatics and comparative genetic analysis and identification of human orthologs, HSB researchers can aid the extrapolation between animal models and human toxicity and disease. Current projects include, but may not be limited to 1)mGenetic analysis of absorption, distribution, metabolism (ADME), genotoxicity, and hematotoxicity phenotypes in multiple inbred mouse strains (NTP-Perlegen haplotyped strains) to low doses of benzene, a model human toxicant and a carcinogen to identify causally related genes and their allelic variants. 2) Development of an experimental short-term cancer bioassays (39 weeks or less) in F1 hybrid p53 haploinsufficient haplotyped strains for genetic analysis to determine haplotype susceptibility to chemical and/or ionizing radiation induced tumorigenesis and identify human orthologs of causally related mouse genes and their allelic variants, and 3) Development of an experimental model genetic analysis of ephedra/caffeine or Bis(2-chloroethoxy)methane induced cardiotoxicity and chemical disposition in multiple inbred mouse strains. After receiving his Ph.D. in comparative biochemistry and molecular toxicology from North Carolina State University at Raleigh, North Carolina, French pursued postdoctoral training in radiobiology at the National Naval Medical Center (NNMC) at the Armed Forces Radiobiology Institute (AFRRI) in Bethesda, Maryland. As a tenured supervisory physiologist at the AFRRI-NNMC he investigated ionizing radiation-induced toxicity and suppression of immune and xenobiotic metabolism systems in multiple model organisms. He also studies the reconstitution of radiation-ablated bone marrow or transfusion therapy with fractionated marrow cells. As a scientist at the National Toxicology Progran (NTP) and NIEHS, French has been involved in toxicology and carcinogenesis studies in laboratory rodents and genetically-modified mouse (GMM) models. In addition, he has collaborated with a number of NIEHS investigators on initiatives that included chemical and radiation induced reactive oxygen species and oxidative stress, and the use of antioxidant and caloric restriction intervention in the suppression of cancer development and implementation of the Host Susceptibility Program for the NTP. Currently, his work focuses on the use of multiple genetically-defined or genetically-modified inbred mouse strains for short term toxicity and cancer phenotypes with the goal of identifying quantitative trait loci of radiation and chemical carcinogen-induced DNA damage and repair in mice and humans.