Analysis of Chronic Exposures to Environmental Toxicants

长期接触环境毒物的分析

• 批准号: 7084038
• 负责人: Kurt D. Pennell
• 金额: $ 14.21万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-08 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7084038
• 关键词: Parkinson' s disease; bioaccumulation; biomarker; chlorohydrocarbon insecticide; dopamine; environmental exposure; environmental toxicology; genetically modified animals; glutathione; hazardous substances; high performance liquid chromatography; high throughput technology; human tissue; laboratory mouse; mass spectrometry; metabolomics; method development; neural degeneration; neurotoxicology; neurotoxins; oxidative stress

DESCRIPTION (provided by applicant) Data compiled over the last two decades indicate that chronic exposure to persistent environmental toxicants, including polychlorinated biphenyls (PCBs) and chlorinated organic insecticides, increases the risk of developing neurodegenerative disease, such as Parkinson's disease (PD). Recent studies suggest that these toxicants contribute to elevated intracellular dopamine levels, increased oxidative stress, and ultimately dopaminergic cell death, a hallmark of PD. The primary objective of this proposal is to rapidly advance the career of the candidate in this field through a combination of didactic learning, mentored research, and multi-disciplinary proposal development. The candidate, Kurt D. Pennell, is an Associate Professor of Environmental Engineering in the School of Civil & Environmental Engineering at the Georgia Institute of Technology. The career development plan, which includes coursework in bioinformatics, advanced spectroscopy and neurotoxicology, builds upon his training in science and engineering, research on contaminant transport and remediation in subsurface systems, analytical skills, and on-going sabbatical in the Department of Neurology at Emory University. The proposed activities will be carried out at Georgia Tech and Emory, where the candidate holds the title of visiting Associate Professor. The underlying hypothesis of the proposed research is that biomarkers of oxidative stress and metabolomic profiles can be correlated to chronic toxicant exposures and neurodegenerative disease. Under the mentorship of Dean P. Jones, Professor and Director of the Emory Clinical Biomarkers Laboratory, the specific aims of the research project are to: 1) Quantify the accumulation and distribution of chlorinated organic compounds in postmortem human tissue and exposed C57BL/6 mice, 2) Assess metabolic disruption and oxidative stress using established HPLC methods and H1-nuclear magnetic resonance (NMR) spectroscopy, and 3) Develop and evaluate a high-throughput, quantitative metabolomic profiling method based on coupled ion exchange liquid chromatography and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Dr. Pennell's career goals are to establish an active research program in environmental metabolomics, play an integral role in multi-disciplinary research teams investigating chronic exposures to environmental toxicants, and to be a leader in fostering linkages between environmental engineering and biomedical sciences. Relevance: The proposal is relevant to public health because it will advance our understanding of the relationship between chronic exposure to environmental toxicants and neurodegenerative disease, provide quantitative methods to rapidly screen for oxidative stress and adverse metabolic profiles, and offer the possibility for early detection and intervention.

描述（由申请人提供） 过去20年汇编的数据表明，长期接触持久性环境毒物，包括多氯联苯和氯化有机杀虫剂，会增加患神经退行性疾病的风险，如帕金森病。 最近的研究表明，这些毒物有助于细胞内多巴胺水平升高，氧化应激增加，并最终导致多巴胺能细胞死亡，这是PD的标志。该提案的主要目标是通过教学学习，指导研究和多学科提案开发的结合，快速推进候选人在该领域的职业生涯。候选人Kurt D.彭内尔是格鲁吉亚理工学院土木与环境工程学院环境工程副教授。职业发展计划，其中包括生物信息学，先进的光谱学和神经毒理学课程，建立在他的科学和工程培训，污染物运输和地下系统修复的研究，分析技能，以及在埃默里大学神经病学系正在进行的休假。拟议的活动将在格鲁吉亚理工学院和埃默里大学进行，候选人拥有客座副教授的头衔。这项研究的基本假设是，氧化应激和代谢组学特征的生物标志物可能与慢性毒物暴露和神经退行性疾病相关。在埃默里临床生物标志物实验室教授兼主任Dean P. Jones的指导下，该研究项目的具体目标是：1）量化死后人体组织和暴露的C57 BL/6小鼠中氯化有机化合物的积累和分布，2）使用已建立的HPLC方法和H1-核磁共振（NMR）光谱法评估代谢破坏和氧化应激，和3）开发和评估基于耦合离子交换液相色谱和傅立叶变换离子回旋共振质谱（FT-ICR MS）的高通量定量代谢组学分析方法。 Pennell博士的职业目标是在环境代谢组学方面建立一个积极的研究计划，在调查长期暴露于环境毒物的多学科研究团队中发挥不可或缺的作用，并成为促进环境工程和生物医学科学之间联系的领导者。 相关性：该提案与公共卫生有关，因为它将促进我们对长期暴露于环境毒物和神经退行性疾病之间关系的理解，提供快速筛查氧化应激和不良代谢特征的定量方法，并提供早期检测和干预的可能性。