The UNC-CH Program's multidisciplinary research will address scientific issues that underpin the assessment and reduction of risks to human health associated with high priority chemicals at Superfund sites. The overall specific aims are to improve the scientific foundation for risk assessment, elucidate mechanisms responsible for inter-individual susceptibility, advance approaches to assessing exposure to hazardous chemicals, and more efficiently reduce risks by remediation of hazardous waste sites. In this competing continuation, we will focus on three major classes of chemicals ~ polycyclic aromatic hydrocarbons (PAHs), halogenated hydrocarbons, and heavy metals ~ in three biomedical and two non-biomedical projects, two Research Support Cores, a Research Translation Core (RTC), and an Administrative Core. Research themes that cross multiple projects and cores include: (1) developing biomarkers of exposure and effect for human and experimental models of environmental disease over a range of exposure levels to improve low-dose quantitative risk assessment;(2) applying new molecular tools in a systems biology framework to understand metabolic pathways critical for environmental disease, predict in vivo inter-individual differences in susceptibility and risk, and evaluate complex microbial communities in bioremediation systems;(3) using advanced analytical tools to identify mechanisms of genotoxicity;(4) using advanced statistical and bioinformatics methods to evaluate gene-environment interactions;and (5) quantifying the chronic exposure and bioavailability of toxic compounds in environmental systems. This work will also be integrated by sharing methods and resources across projects and cores, by regular meetings of all researchers, and by co-advising of trainees by faculty in different projects and cores. Working with investigators, the RTC will enhance the capacity of government agencies to provide technical assistance to communities, develop improved decision-support tools, and promote the commercialization of our research products. This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity.
This Program is relevant to public health because it will develop better means of quantifying risks to human health from exposure to hazardous chemicals, provide a genetic basis for susceptibility to diseases caused by these chemicals, improve methods to monitor exposure, and advance methods of reducing risks through remediation of contaminated sites.
|Martin, Elizabeth M; Stýblo, Miroslav; Fry, Rebecca C (2017) Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence. Epigenomics 9:701-710|
|Luo, Yu-Syuan; Cichocki, Joseph A; McDonald, Thomas J et al. (2017) Simultaneous detection of the tetrachloroethylene metabolites S-(1,2,2-trichlorovinyl) glutathione, S-(1,2,2-trichlorovinyl)-L-cysteine, and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in multiple mouse tissues via ultra-high performance liquid chromatog J Toxicol Environ Health A 80:513-524|
|Grimm, Fabian A; Russell, William K; Luo, Yu-Syuan et al. (2017) Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass Spectrometry to Enable Chemical Composition-Based Read-Across. Environ Sci Technol 51:7197-7207|
|Smeester, Lisa; Bommarito, Paige A; Martin, Elizabeth M et al. (2017) Chronic early childhood exposure to arsenic is associated with a TNF-mediated proteomic signaling response. Environ Toxicol Pharmacol 52:183-187|
|McEachran, Andrew D; Shea, Damian; Nichols, Elizabeth Guthrie (2017) Pharmaceuticals in a temperate forest-water reuse system. Sci Total Environ 581-582:705-714|
|Huang, Madelyn C; Douillet, Christelle; Su, Mingming et al. (2017) Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure. Arch Toxicol 91:189-202|
|Zhou, Yi-Hui; Cichocki, Joseph A; Soldatow, Valerie Y et al. (2017) Editor's Highlight: Comparative Dose-Response Analysis of Liver and Kidney Transcriptomic Effects of Trichloroethylene and Tetrachloroethylene in B6C3F1 Mouse. Toxicol Sci 160:95-110|
|Gao, Lina; Mutlu, Esra; Collins, Leonard B et al. (2017) DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure. Chem Res Toxicol 30:794-803|
|Nakamura, Jun; Shimomoto, Takasumi; Collins, Leonard B et al. (2017) Evidence that endogenous formaldehyde produces immunogenic and atherogenic adduct epitopes. Sci Rep 7:10787|
|Brooks, Samira A; Fry, Rebecca C (2017) Cadmium inhibits placental trophoblast cell migration via miRNA regulation of the transforming growth factor beta (TGF-?) pathway. Food Chem Toxicol 109:721-726|
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