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.
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.
|Nault, Rance; Doskey, Claire M; Fader, Kelly A et al. (2018) Comparison of Hepatic NRF2 and Aryl Hydrocarbon Receptor Binding in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Treated Mice Demonstrates NRF2-Independent PKM2 Induction. Mol Pharmacol 94:876-884|
|Dornbos, Peter; LaPres, John J (2018) Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population. Toxicology 395:1-8|
|Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Interfacial Structure and Interaction of Kaolinite Intercalated with N-methylformamide Insight from Molecular Dynamics Modeling. Appl Clay Sci 158:204-210|
|Fader, Kelly A; Nault, Rance; Raehtz, Sandi et al. (2018) 2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice. Toxicol Appl Pharmacol 348:85-98|
|Zhang, Shuai; Liu, Qinfu; Cheng, Hongfei et al. (2018) Mechanism Responsible for Intercalation of Dimethyl Sulfoxide in Kaolinite: Molecular Dynamics Simulations. Appl Clay Sci 151:46-53|
|Zhang, Qiang; Li, Jin; Middleton, Alistair et al. (2018) Bridging the Data Gap From in vitro Toxicity Testing to Chemical Safety Assessment Through Computational Modeling. Front Public Health 6:261|
|Fader, K A; Nault, R; Kirby, M P et al. (2018) Corrigendum to ""Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity"" [Toxicol. Appl. Pharmacol. 321 (2017) 1-17]. Toxicol Appl Pharmacol 344:74|
|Konganti, Kranti; Ehrlich, Andre; Rusyn, Ivan et al. (2018) gQTL: A Web Application for QTL Analysis Using the Collaborative Cross Mouse Genetic Reference Population. G3 (Bethesda) 8:2559-2562|
|Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Molecular Dynamics Simulation of Basal Spacing, Energetics, and Structure Evolution of a Kaolinite-Formamide Intercalation Complex and Their Interfacial Interaction. J Phys Chem C Nanomater Interfaces 122:3341-3349|
|Williams, M R; Stedtfeld, R D; Waseem, H et al. (2017) Implications of direct amplification for measuring antimicrobial resistance using point-of-care devices. Anal Methods 9:1229-1241|
Showing the most recent 10 out of 417 publications