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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004696-23
Application #
7808047
Study Section
Special Emphasis Panel (ZES1-LKB-D (S8))
Program Officer
Thompson, Claudia L
Project Start
1997-04-01
Project End
2014-03-31
Budget Start
2010-04-20
Budget End
2011-03-31
Support Year
23
Fiscal Year
2010
Total Cost
$2,342,413
Indirect Cost
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Criswell, Susan R; Warden, Mark N; Searles Nielsen, Susan et al. (2018) Selective D2 receptor PET in manganese-exposed workers. Neurology 91:e1022-e1030
Meador, James P; Yeh, Andrew; Gallagher, Evan P (2018) Adverse metabolic effects in fish exposed to contaminants of emerging concern in the field and laboratory. Environ Pollut 236:850-861
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Heffern, Kevin; Tierney, Keith; Gallagher, Evan P (2018) Comparative effects of cadmium, zinc, arsenic and chromium on olfactory-mediated neurobehavior and gene expression in larval zebrafish (Danio rerio). Aquat Toxicol 201:83-90
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Rooney, James P K; Woods, Nancy F; Martin, Michael D et al. (2018) Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children. Environ Res 165:1-10
Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2018) Prenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice. Part Fibre Toxicol 15:18
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2018) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology 64:43-49
Wang, Hao; Zhang, Liang; Abel, Glen M et al. (2018) Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice. Toxicol Sci 161:87-102

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