The MIT Superfund Research Program: A Systems Approach for the Protection of Human Health from Hazardous Chemicals

麻省理工学院超级基金研究计划：保护人类健康免受危险化学品侵害的系统方法

• 批准号: 10351931
• 负责人: Bevin P. Engelward
• 金额: $ 225.03万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10351931
• 关键词: Address; Animal Model; Biochemical; Biological; Biological Assay; Biomedical Research; Carcinogens; Cells; Cellular Phone; Chemicals; Chloramines; Coal; Collection; Communication; Communities; DNA Damage; DNA Sequence Alteration; Data; Data Analyses; Development; Devices; Dimethylnitrosamine; Disease; Dose; Educational process of instructing; Engineering; Ensure; Environment; Environmental Engineering technology; Environmental Science; Evaluation; Exposure to; Family; Filtration; Food; Gas Chromatography; Genetic Engineering; Global Warming; Goals; Government; Hazardous Chemicals; Hazardous Substances; Hazardous Waste Sites; Health; Human; Induced Mutation; Intervention; Knowledge; Learning; Light; Machine Learning; Malignant Neoplasms; Mammalian Cell; Mass Spectrum Analysis; Measures; Mediating; Methods; Microarray Analysis; Mission; Multiomic Data; Municipalities; Mutagens; Mutation; N-nitrosodimethylamine; Names; Nanotechnology; National Institute of Environmental Health Sciences; Nitrosamines; Nitroso Compounds; Pathway interactions; Personal Satisfaction; Persons; Pharmaceutical Preparations; Population Growth; Postdoctoral Fellow; Probiotics; Public Health; Recipe; Research; Research Project Grants; Research Support; Risk; Role; Scientist; Serinus; Site; Source; Statistical Data Interpretation; Structure; Sum; Superfund; System; Systems Biology; Technology; Testing; Toxic effect; Training; Translational Research; Translations; Tribes; United States Environmental Protection Agency; Water; Work; adverse outcome; analytical method; analytical tool; base; cancer risk; carcinogenicity; career; citizen science; community engagement; data management; data sharing; data streams; detector; disorder prevention; drinking water; environmental justice; experience; graduate student; innovation; mathematical analysis; meetings; member; mouse model; new technology; novel; optical sensor; predictive marker; prevent; programs; remediation; response; sensor; sensor technology; superfund chemical; superfund site; synergism; training opportunity; transcriptome; wasting; water sampling; well water

PROJECT SUMMARY/ABSTRACT – OVERALL N-Nitrosamines are a family of hazardous chemicals that are among the most mutagenic chemicals known, and many are potently carcinogenic in animal models. People living in Wilmington, MA, are concerned about N- nitrosamines because there are over 20 million gallons of N-nitrosamine-contaminated waste at the nearby Olin Chemical Superfund Site, contaminating the environment and rendering their well water undrinkable. The Passamaquoddy Tribe is also concerned about N-nitrosamines, because their water contains high levels of organic material and the use of chloramine is known to create N-nitrosodimethylamine. Specific Aim 1 is to make and measure. Innovative, light-based chemical sensors that exploit smartphones will be created and used for Citizen Science to gain information that will help to inform cleanup by the Environmental Protection Agency (EPA). Innovative, high-throughput `animate sensors,' based on cell-microarray technology, will be created and used to test the consequences of N-nitrosamines on health-related impacts known to be associated with cancer risk. To understand disease more deeply, a genetically engineered “canary in the coal mine” mouse model will be used to reveal the potential for long-term low-dose exposure to cause mutations and deleterious biological responses. Specific Aim 2 is to protect human health via prediction and prevention of disease. By integrating multi-omics data (fueled by the Data Management and Analysis Core [DMAC]), mechanistic knowledge will propel the development of predictive biomarkers that can be used to develop methods to prevent disease. The potential for probiotics to suppress N-nitrosamine-induced cancer will be studied. In addition, novel devices will be created to destroy N-nitrosamines via electrochemical and biochemical destruction. Importantly, risk evaluation depends on knowledge from both engineers and biologists. The DMAC will thus form a critical integrating role by merging transdisciplinary data streams to evaluate risk for specific water samples. Specific Aim 3 is to maximize societal impact via integration within the MIT SRP and with partners outside of MIT. Partnering with the community will allow collection of environmental data that will inform risk. Via bidirectional communication, community members will also benefit from novel, hands-on teaching kits, while MIT SRP members will benefit from learning about community perspectives and concerns. Dissemination of MIT SRP knowledge and technologies will also be achieved via continued strengthening of relationships between the MIT SRP and local, state, Tribal and governmental agents, including community members who are most impacted by N-nitrosamine contamination. All of this work will be made possible by careful coordination and formalization of translation opportunities (made possible by the Administrative Core), and by continuous improvement of training opportunities that not only fuel the research (made possible by the Research Experience and Training Coordination Core [RETCC]), but also help to ensure that trainees go on to contribute as responsible leaders who are able to leverage cross-disciplinary research in order to have a powerful impact on public health.

项目总结/摘要-总体 N-亚硝胺是一系列危险化学品，是已知最具致突变性的化学品之一， 许多在动物模型中是潜在的致癌物。生活在马萨诸塞州威尔明顿的人们担心N- 亚硝胺，因为有超过20万加仑的N-亚硝胺污染的废物在附近的奥林 化学超级基金网站，污染环境，使他们的井水不能饮用。的 帕萨马科迪部落也担心N-亚硝胺，因为他们的水含有高水平的 已知有机材料和使用氯胺产生N-亚硝基二甲胺。具体目标1是 制作和测量。将创建和使用利用智能手机的创新光基化学传感器 公民科学获得的信息将有助于环境保护局的清理工作 （EPA）。将建立基于细胞微阵列技术的创新的、高通量的“生物传感器”， 用于测试N-亚硝胺对已知与癌症相关的健康影响的后果 风险为了更深入地了解疾病，一种基因工程的“煤矿里的金丝雀”小鼠模型将 用于揭示长期低剂量暴露导致突变和有害生物的可能性 应答具体目标2是通过预测和预防疾病来保护人类健康。通过 整合多组学数据（由数据管理和分析核心[DMAC]推动）， 知识将推动预测生物标志物的发展，这些生物标志物可用于开发预防方法， 疾病将研究益生菌抑制N-亚硝胺诱导的癌症的潜力。此外，小说 通过电化学和生物化学的方法来破坏N-亚硝胺。重要的是， 风险评估取决于工程师和生物学家的知识。因此，DMAC将形成关键的 通过合并跨学科数据流来评估特定水样的风险，发挥综合作用。具体 目标3是通过在麻省理工学院SRP内部以及与麻省理工学院以外的合作伙伴的整合，最大限度地发挥社会影响。 与社区建立伙伴关系将有助于收集环境数据，为风险提供信息。经由双向 交流，社区成员也将受益于新颖的，动手教学套件，而麻省理工学院SRP 成员将从了解社区的观点和关注中受益。MIT SRP的传播 知识和技术也将通过不断加强与麻省理工学院之间的关系来实现 SRP和地方、州、部落和政府机构，包括受影响最大的社区成员 被N-亚硝胺污染所有这些工作都将通过认真协调和正规化来实现 翻译机会的增加（通过行政核心得以实现）， 培训机会，不仅推动研究（通过研究经验和培训成为可能） 协调核心[RETCC]），但也有助于确保受训人员继续作为负责任的领导人作出贡献 他们能够利用跨学科的研究，以便对公共卫生产生强大的影响。