This proposal is for a 5-year competing renewal of the University of Washington (UW) Superfund Basic Research Program Project. The theme of this program is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures;b) early indicators of damage;and/or c) unusual susceptibility to toxic agents that commonly occur at Superfund sites. The proposed UW Program includes 5 research projects (3 biomedical, 2 non-biomedical [ecotoxicology, bioremediation]), 2 of which are new (both biomedical). The program will focus most intensively on biomarker applications for investigations of adverse effects to human health and the environment from neurotoxic chemicals, primarily metals and pesticides. Collectively, these projects will develop and validate biomarkers for: elucidating underlying neurotoxicity mechanisms in humans and animal models;identifying early-stage neurologic disease processes in humans;characterizing dose-response relations for selected neurotoxicants with neurologic disease risk, severity, and progression, using PS as a model outcome;and, for implementing phytoremediation techniques. The research projects include studies of: 1) animal models of susceptibility to organophosphate pesticides, with applications to pesticide-exposed farmworkers and to persons affected with Parkinson's disease;2) metals and Parkinsonism among professional welders;3) proteomic markers of metal-induced PS;4) sub-lethal neurotoxic effects of metals and pesticides in free-living Coho salmon;and, 5) phytoremediation methods for organic solvents and pesticides. The Administrative Core will oversee all budgetary and reporting aspects of the Program, and will foster multidisciplinary interactions among projects and cores. The Functional Genomics and Bioinformatics Core will provide extensive molecular biology laboratory and data analysis support to all research projects. The Research Translation Core will ensure timely and appropriate communication of our research findings to relevant stakeholders, including government agencies, community groups, and the private sector.

Public Health Relevance

Many chemical exposures that occur at Superfund waste sites can adversely affect human health, wildlife, and the environment. This program, which focuses on developing biological markers of chemicals that can damage the nervous system, will add to the understanding of how some chemicals are hazardous and will advance methods for reducing waste site exposures.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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Special Emphasis Panel (ZES1-LKB-D (S8))
Program Officer
Thompson, Claudia L
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University of Washington
Public Health & Prev Medicine
Schools of Public Health
United States
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Meador, James P; Yeh, Andrew; Gallagher, Evan P (2017) Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations. Environ Pollut 230:1018-1029
Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2017) Behavioral Phenotyping for Autism Spectrum Disorders in Mice. Curr Protoc Toxicol 72:11.22.1-11.22.21
Roqué, Pamela J; Costa, Lucio G (2017) Co-Culture of Neurons and Microglia. Curr Protoc Toxicol 74:11.24.1-11.24.17
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Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara et al. (2017) Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2017) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology :

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