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Environmental Genomics Group

Variation in Toxicological Responses

Douglas A. Bell, Ph.D.
Douglas A. Bell, Ph.D.
Principal Investigator

Tel (919) 541-7686
Fax (919) 541-4634

P.O. Box 12233
Mail Drop C3-03
Research Triangle Park, North Carolina 27709
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Research Summary

The Environmental Genomics Group works to characterize the role of genetic variation in human toxicological responses, especially to discover human alleles that modify responses to exposure and to investigate how such alleles affect risk in exposed people. This information is useful in determining appropriate variability parameters in human risk estimation models, in identifying at-risk individuals and in devising disease-prevention strategies.

Having uncovered the genetic basis for several phenotypes in carcinogen metabolism, the group has developed high-throughput genotyping assays and worked with epidemiologists to further explore the gene-environment interaction component of disease. Several genotypes affecting carcinogen metabolism and DNA repair have been identified as susceptibility factors in environmentally-induced disease.

The NIEHS Environmental Genome Project ( and other single nucleotide polymorphism (SNP) discovery projects are uncovering millions of sequence variants in the human genome. However, relatively few of these SNPs affect protein structure. Perhaps more will affect gene expression related to environmental stress responses. At present, there are no established methods to identify SNPs that regulate gene expression or to measure their functional impact in vivo. Thus, the group’s overall objective is to identify sequence variants that modulate exposure responses and to evaluate their roles in human susceptibility to environmentally-induced disease.

Major areas of research:

  • Genetic variation in human toxicological responses
  • Identification of sequence variants that modulate exposure responses
  • Evaluation of the role of those variants in environmentally-induced disease

Current projects:

  • Computational discovery and functional analysis of SNPs in p53 and NRF2 transactivation target sequences (response elements). The group is developing and applying novel bioinformatics methods including phylogenetic analysis and functional assays to assess the impact of SNPs on regulatory elements in p53- and NRF2-responsive genes.
  • Discovery and functional analysis of genetic factors predisposing to oxidant injury. The group is analyzing SNPs in genes that are regulated by oxidative stress, and carrying out functional genomics studies to elucidate their significance as susceptibility factors.
  • Following the discovery of a functional SNP in the promoter of the GSTM3 gene, the group is evaluating how GSTM3 expression alters growth in glioma cells and impacts sensitivity to chemotherapeutic agents.

Douglas A. Bell, Ph.D., heads the Environmental Genomics Group within the Laboratory of Molecular Genetics. He received his Ph.D. in environmental chemistry and biology from the University of North Carolina at Chapel Hill in 1988. He has published over 120 peer-reviewed articles in leading biomedical journals, as well as several book chapters. He served as a National Research Council Fellow at the U.S. Environmental Protection Agency before joining NIEHS in 1990.

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Last Reviewed: January 02, 2009