Host Susceptibility Branch

Research Summary

The Host Susceptibility Branch (HSB), headed by Acting Branch Chief John E. French, Ph.D. (http://www.niehs.nih.gov), is critical to the National Toxicology Program’shttp://ntp-server.niehs.nih.gov/ development, testing, and analysis of new in vivo and in vitro models for investigation of chemical exposure and related disease.

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The primary aim of the branch research is to develop new laboratory models and testing protocols for hazard identification and risk assessment that are based upon the quantitative differences in the variable range of response between individuals 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 that cause toxicity, including idiosyncratic drug toxicities. The goal of the HSB is to model this genetic diversity in the human population using genetically diverse laboratory animals for in vivo and in vitro toxicology studies.

To meet this aim, the HSB scientists are:

• Planning, conducting and analyzing research on chemical toxicity using multiple genetically-defined and/or genetically-modified animal models
• Developing the research base for internal and external research collaborations to promote investigation of the genetic basis for individual differences in susceptibility to toxicity and disease

The HSB identifies the quantitative trait loci by genetic analysis (meiotic mapping, haplotype-phenotype segregation analysis, etc.) and conducts functional validation of the candidate genes to identify their allelic variants that modify individual response to chemical exposure and disease. By doing so, the branch aims to identify the key genes and pathways that modify or influence an individual response — and, thus, the variance observed within a population of individuals — to chemical exposures of presumed or known risk to humans. Using the tools of toxicology, bioinformatics and comparative genetic analysis, the identification of human orthologs of causally-related animal genes will aid the extrapolation between animal models and human toxicity and disease related to environmental, occupational, and/or medicinal exposures.

Scientific Support Staff

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