Douglas A. Bell
Institut Pasteur de Bangui
Douglas A. Bell, Ph.D., heads the Environmental Epigenomics and Disease Group and holds secondary appointments in the NIEHS Epigenetics and Stem Cell Laboratory and the NIEHS Genome Integrity and Structural Biology Laboratory. The Environmental Epigenomics and Disease Group works to characterize underlying factors that contribute to variability in human toxicological responses. We especially focus on discovery of human alleles and epigenetic factors that modify responses to exposure and we investigate how such factors affect risk in exposed people. This basic information will be useful for understanding variability in human risk estimation models, and potentially, for identifying at-risk individuals and devising disease-prevention strategies. Having uncovered the genetic basis for several susceptibility 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 exposure-induced disease. Several genotypes affecting carcinogen metabolism and DNA repair have been identified as susceptibility factors in environmentally-induced disease. The group’s gene-environment interaction studies on polymorphisms in GSTM1 (Bell et al., 1993) and N-acetyltransferase (Taylor et al., 1998) in bladder cancer have been highly cited.
Identification of epigenetic factors and sequence variants that modulate exposure responses regulated by the Ah receptor (carcinogen metabolism), NRF2 (oxidative stress), and p53 (DNA damage) (Figure 1). Evaluation of the role of these factors in environmentally-induced disease.
Current projects: Computational discovery and functional analysis of p53 and NRF2 transactivation target sequences (response elements) (Tomso et al., 2005; Wang et al., 2007; Bandele et al 2011; Chorley et al., 2012) (Figure 1a). The group is developing and applying novel bioinformatics methods including phylogenetic analysis (Horvath et al., 2007; Wang et al., 2007) and new functional assays to assess the impact of SNPs on regulatory elements in p53; (Noureddine et al., 2009; Bandele et al., 2011; Zeron-Median et al., 2013; Wang et al., 2015) and NRF2-responsive genes (Wang et al 2011). These studies will help us understand the role of chromatin state, dynamics, and methylation status on exposure-induced transcription of genes in the p53, AhR and NRF2 pathways