The goal of this proposal is to develop a Center for Indigenous Environmental Health Research (CIEHR), partnering with American Indian and Alaska Native (AI/AN) communities to build capacity to determine the contribution of chemical and other environmental exposures to health inequities and support efforts to address these threats. AI/AN communities suffer from increased mortality attributable to cancer (stomach, gallbladder, liver and kidney), respiratory disease, diabetes, and liver disease, among other conditions. Chemically contaminated traditional foods, water, air, and household environments, as well as social determinants of health, contribute to these health disparities and stand out as modifiable factors for AI/AN communities. Effective and sustainable environmental health disparities research and mitigation require a community-based participatory research (CBPR) approach, engaging the strengths of AI/AN communities and providing data and context to inform policy decisions. Nascent research on resilience in AI/AN and other peoples identifies traditional community structure and social relationships, cultural identity and practices, and experience with past adversity as protective, offering innovative directions for AI/AN health research and intervention. CIEHR will address these challenges and opportunities through completion of the following specific aims: 1) Partner with indigenous communities to carry out environmental exposure research; 2) Build indigenous community capacity to address environmental health inequities; and 3) Improve environmental health research translation and inform health policy. CIEHR components will include: an Administrative Core (AC) including AI/AN Career Development Investigators (CDIs); a Community Engagement Core (CEC); an Exposure Science Core (ESC); Research Project 1 Health and Wellbeing Impact of Contamination of Traditional Food and Water on the Navajo; Research Project 2 Cumulative Environmental Effects: Expanding Research with the Hopi Tribe; and the Pilot Projects Core (PPC). Employing a CBPR approach, CIEHR will respond to Navajo requests to evaluate contamination of traditional food and water sources by uranium and arsenic and address Hopi Tribe concerns regarding household exposures to arsenic, uranium and particulate matter. Pilot research projects will focus on additional AI/AN partnerships to evaluate exposures on tribal lands and in urban and rural off-reservation settings. CIEHR will work with AI/AN partners to strengthen community resilience, increase environmental health literacy, and help translate and disseminate the research findings to inform community strategies to reduce adverse environmental exposures. CIEHR will identify mechanisms for effectively partnering with AI/AN communities to use exposure assessment to address their environmental health concerns, determine how to best strengthen tribal resilience to mitigate adverse environmental exposures, and provide exemplars of how to use research to support sustainable tribal environmental health approaches.