Effects-Related Biomarkers of Environmental Neurotoxic Exposures

该提案是华盛顿大学（UW）超级基金基础研究计划项目为期5年的竞争性更新。这个项目的主题是，在可接触的组织中测量的生物标志物可以预测：a)有毒物质暴露；B)损害的早期指标；和/或c)对通常发生在超级基金场所的有毒物质的异常易感性。UW计划包括5个研究项目（3个生物医学，2个非生物医学[生态毒理学，生物修复]），其中2个为新项目（均为生物医学）。该项目将集中研究生物标志物的应用，用于研究神经毒性化学物质（主要是金属和农药）对人类健康和环境的不利影响。总的来说，这些项目将开发和验证生物标志物：阐明人类和动物模型中潜在的神经毒性机制；识别人类早期神经系统疾病过程；使用PS作为模型结果，表征选定的神经毒物与神经疾病风险、严重程度和进展的剂量-反应关系；以及实施植物修复技术。研究项目包括：1)对有机磷农药易感性的动物模型，并将其应用于接触农药的农场工人和帕金森病患者；2)专业焊工的金属与帕金森病；3)金属诱导PS的蛋白质组学标记；4)金属和农药对自由生活银鲑的亚致死神经毒性作用；5)有机溶剂和农药的植物修复方法。行政核心将监督该计划的所有预算和报告方面，并将促进项目和核心之间的多学科互动。功能基因组学和生物信息学核心将为所有研究项目提供广泛的分子生物学实验室和数据分析支持。研究翻译核心将确保我们的研究成果及时和适当地传达给相关利益相关者，包括政府机构、社区团体和私营部门。

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.