Support is requested to continue human health-oriented research on risks from exposure to chemicals commonly found in Superfund sites and on remediation technologies to eliminate the potential for exposure to chemicals from those sites. The pollutants under investigation are a subclass of chemicals belonging to the halogenated aromatic hydrocarbon family that bind and activate the aryl hydrocarbon receptor (AhR). These chemicals, which include chlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and polyaromatic hydrocarbons, are environmentally persistent, lipid soluble that accumulate in the food chain leading to human and wildlife exposure. A highly integrated, multidisciplinary research program is proposed consisting of six research projects and six supporting core units. The research team of 25 investigators includes faculty at Michigan State University (18), the Hamner Institutes for Health Sciences (4), Rutgers University (2), Purdue University (1) and United States Environmental Protection Agency (1). The central overarching theme of the proposed program is to define specific aspects of environmental, microbial and mammalian biomolecular responses to environmental contaminants that act as ligands for the AhR. The major research thrusts will provide new mechanistic information in three areas: (1) characterizing the diversity and physiogenomic responses of (chloro)dioxin degrading microbial populations indigenous to soils, sediments and groundwater;(2) defining the geochemical parameters governing adsorption, bioavailability and long-term fate of AhR ligands through interactions with geosorbent compositions in soils and sediment components;and (3) elucidation and computational modeling of the interactions of specific biochemical pathways with the ligand-activated AhR which cause altered responses in the liver and immune system with a particular emphasis on responses by human primary cells. One research core will assist the biomedical projects, in developing dynamic computational models of mammalian responses induced by AhR ligands. A second research core will provide bioinformatics support and custom bioinformatics tool development, along with development of a novel molecular method for enriching metagenomes and metatranscriptomes in functional genes of interest to project 4 (biomedical), 5 and 6 (environmental). In addition, a Research Translation Core will communicate research findings to appropriate target audiences in government, industry and academia, a Community Engagement Core will communicate with community target audiences, and a Training Core will provide cross-disciplinary training to pre- and postdoctoral students.

Public Health Relevance

Environmental pollutants that act as aryl hydrocarbon receptor agonists are ubiquitous contaminants and occupy a significant percentage of the 2007 Superfund Priority List of Hazardous Substances, including three of the top ten positions. This program will conduct human health-oriented research on risks from exposure to these chemicals commonly found in Superfund sites and on remediation technologies to eliminate the potential for exposure to chemicals from those sites.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
3P42ES004911-23S1
Application #
8898977
Study Section
Special Emphasis Panel (ZES1-LWJ-D (SF))
Program Officer
Henry, Heather F
Project Start
1997-04-01
Project End
2015-03-31
Budget Start
2014-08-05
Budget End
2015-03-31
Support Year
23
Fiscal Year
2014
Total Cost
$49,939
Indirect Cost
$15,394
Name
Michigan State University
Department
Pharmacology
Type
Schools of Veterinary Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Stedtfeld, Robert D; Stedtfeld, Tiffany M; Waseem, Hassen et al. (2017) Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers. J Environ Manage 198:213-220
Fader, Kelly A; Nault, Rance; Zhang, Chen et al. (2017) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism. Sci Rep 7:5921
Waseem, Hassan; Williams, Maggie R; Stedtfeld, Tiffany et al. (2017) Virulence factor activity relationships (VFARs): a bioinformatics perspective. Environ Sci Process Impacts 19:247-260
Fader, Kelly A; Nault, Rance; Kirby, Mathew P et al. (2017) Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity. Toxicol Appl Pharmacol 321:1-17
Kovalova, Natalia; Nault, Rance; Crawford, Robert et al. (2017) Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells. Toxicol Appl Pharmacol 316:95-106
Samhan, Farag A; Stedtfeld, Tiffany M; Waseem, Hassan et al. (2017) On-filter direct amplification of Legionella pneumophila for rapid assessment of its abundance and viability. Water Res 121:162-170
Li, Jinpeng; Bhattacharya, Sudin; Zhou, Jiajun et al. (2017) Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis. J Immunol 199:3504-3515
Stedtfeld, Robert D; Brett Sallach, J; Crawford, Robert B et al. (2017) TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal. Appl Microbiol Biotechnol 101:7409-7415
Dornbos, Peter; LaPres, John J (2017) Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population. Toxicology 395:1-8
Ahmad, Farhan; Stedtfeld, Robert D; Waseem, Hassan et al. (2017) Most probable number - loop mediated isothermal amplification (MPN-LAMP) for quantifying waterborne pathogens in <25min. J Microbiol Methods 132:27-33

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