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 #
5P42ES004696-26
Application #
8451553
Study Section
Special Emphasis Panel (ZES1-LKB-D (S8))
Program Officer
Carlin, Danielle J
Project Start
1997-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
26
Fiscal Year
2013
Total Cost
$2,195,825
Indirect Cost
$745,686
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
Furlong, Clement E; Marsillach, Judit; Jarvik, Gail P et al. (2016) Paraoxonases-1, -2 and -3: What are their functions? Chem Biol Interact :
Cole, Toby B; Coburn, Jacki; Dao, Khoi et al. (2016) Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain. Toxicology 374:1-9
Roqué, Pamela J; Dao, Khoi; Costa, Lucio G (2016) Microglia mediate diesel exhaust particle-induced cerebellar neuronal toxicity through neuroinflammatory mechanisms. Neurotoxicology 56:204-214
Garrick, Jacqueline M; Dao, Khoi; de Laat, Rian et al. (2016) Developmental expression of paraoxonase 2. Chem Biol Interact 259:168-174
Ramsden, Richard; Gallagher, Evan P (2016) Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets. Redox Biol 9:114-123
Meador, James P; Yeh, Andrew; Young, Graham et al. (2016) Contaminants of emerging concern in a large temperate estuary. Environ Pollut 213:254-67
Wang, Lu; Espinoza, Herbert M; MacDonald, James W et al. (2016) Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury. Toxicol Sci 149:145-57
Marsillach, Judit; Costa, Lucio G; Furlong, Clement E (2016) Paraoxonase-1 and Early-Life Environmental Exposures. Ann Glob Health 82:100-10
Costa, Lucio G; Garrick, Jacqueline M; Roquè, Pamela J et al. (2016) Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More. Oxid Med Cell Longev 2016:2986796
Kim, Daniel Seung; Burt, Amber A; Ranchalis, Jane E et al. (2015) PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity. J Lipid Res 56:1351-62

Showing the most recent 10 out of 427 publications