This project of the Environmental Stress and Cancer Group investigates the molecular mechanisms of responses to environmental stresses involved in the etiology and progression of injury and disease processes. The overall goal of these studies is to provide a better understanding of the regulatory networks that control critical cellular responses to environmental stresses. Our approach utilizes advances in genomics and bioinformatics to address critical threats to human health as a consequence of environmental exposures. Specifically, the group is designing, executing, and analyzing studies that integrate global """"""""omics"""""""" approaches with conventional studies of environmental stress, toxicity and disease processes. Core to these toxicogenomic efforts is the concept of phenotypic anchoring, in which studies are designed to relate alterations in gene expression to adverse effects defined by conventional parameters of toxicity and pathology. Studies are designed to provide insight into mechanisms of injury and disease as well as to establish signatures of adverse effects to develop putative biomarkers. These studies have utilized agents at multiple doses and times of treatment to fully explore ranges of biological responses to those agents. Analyses that implicate a critical role of a particular biological process or of a particular gene in an adverse response are followed up with additional experiments designed to test hypotheses concerning these roles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES023026-09
Application #
7593876
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2007
Total Cost
$511,374
Indirect Cost
City
State
Country
United States
Zip Code
Ferrucio, Bianca; Tiago, Manoela; Fannin, Richard D et al. (2017) Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes. Toxicol In Vitro 38:67-76
Cui, Yuxia; Huang, Qihong; Auman, James Todd et al. (2011) Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity. Toxicol Sci 124:23-34
Kienhuis, Anne S; van de Poll, Marcel C G; Wortelboer, Heleen et al. (2009) Parallelogram approach using rat-human in vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans. Toxicol Sci 107:544-52
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Auman, J Todd; Chou, Jeff; Gerrish, Kevin et al. (2007) Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. Environ Health Perspect 115:572-8
Auman, J Todd; Boorman, Gary A; Wilson, Ralph E et al. (2007) Heat map visualization of high-density clinical chemistry data. Physiol Genomics 31:352-6
Powell, Christine L; Kosyk, Oksana; Ross, Pamela K et al. (2006) Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver. Toxicol Sci 93:213-22
Innes, Cynthia L; Heinloth, Alexandra N; Flores, Kristina G et al. (2006) ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts. Mol Cancer Res 4:197-207
Leung, Elo; Bushel, Pierre R (2006) PAGE: phase-shifted analysis of gene expression. Bioinformatics 22:367-8
Zhang, Donghui; Stumpo, Deborah J; Graves, Joan P et al. (2006) Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development. J Neurochem 98:860-75

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