Pacific Northwest Center for Translational Environmental Health Research

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OVERALL SUMMARY A dominant paradigm of environmental health science is the adverse outcome pathway. The adverse outcome pathway contains an external segment and an internal segment. The external segment is a toxic chemical that comes into contact with a person. That chemical may come from air, water, soil, or diet. The internal segment of the outcome pathway consists of a chain of events: the chemical interacts with a biological target, which triggers events that in turn lead to organ responses, organism responses, and population responses. This framework supports the most important environmental health science questions of our era: What chemical exposures cause disease? How do they cause disease? Why are some people more susceptible than others? How can we predict toxicity? How can we mitigate the impacts of hazardous chemicals? How can we reduce the use of toxic chemicals in commerce? To answer these questions, the OSU EHS CC has an established world-leading position in two of the world's most powerful technologies for investigating the adverse outcome pathway. To study the external segment, the Chemical Exposure (CXC) Facility Core has developed passive sampling wristbands that capture volatile and semi-volatile organic chemicals, as well as analytical techniques that can detect and quantify 1,500 compounds in a single run at low cost. To study the internal segment, the Zebrafish Biomedical Research (ZBR) Facility Core has built the world's largest specific-pathogen-free (i.e., low- experimental-noise) zebrafish environmental health sciences facility. Robots evaluate locomotor activity and look for physical and behavioral endpoints. Full-genome transcriptomics analyses reveal which gene expressions change before the phenotype changes. Together, the CXC and the ZBR give our investigators uniquely powerful experimental capabilities in EHS. Furthermore, these technologies are more than complementary; they are synergistic. We have applied wristband extracts as direct input to the zebrafish bioassay and identified the most toxic compounds in chemical mixtures via effects-directed analysis. Our Integrated Health Sciences Facilities and Community Engagement Cores will make these capabilities available to the extended EHS community via a new translational research model. We plan to co-produce knowledge with stakeholders in seven categories (residential communities, legislators, regulators, manufacturers, health care providers, pharmaceutical firms, and non-profit organizations). EHS CC members will conduct cross- sectoral multidisciplinary research with these stakeholders in order to generate actionable scientific evidence to guide stakeholder decisions that will improve environmental public health.