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

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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.