PROJECT SUMMARY (Overall Core: Maier and Zhang)The University of Arizona Superfund Research program (UA SRP) addresses the unique human health risksencountered in the US Southwest an area with a rich history and future of mining. The Southwest has distinctgeologic and climatic attributes that affect human health and exposures to pollution. Groundwater in Southwestregions with rich ore deposits often has elevated arsenic levels leading to exposure from drinking water.Exposure also occurs by inhalation and ingestion of arsenic-associated mining dusts transported from miningsites into the interior of homes and to exterior environments. Importantly arsenic exposure has been linked tothe development of diabetes. Vulnerable populations residing near mining sites including Native Americans andHispanic communities exhibit increased incidence of diabetes. Our goal is to determine how chronic exposureto mine wastes that contain arsenic contributes to the development of diabetes. We will then use this informationto help predict exposures and associated health outcomes as well as to inform public health prevention strategiesin communities that neighbor mine waste sites. To achieve this goal we have five research projects and fourcores that will: 1) characterize how chronic mine waste arsenic exposure in mining impacted areas is linked todiabetogenic outcomes through mediation of Nrf2 signaling; 2) determine how the gut microbiome and miningwaste mineral properties influence arsenic species transformation bioavailability and toxicity; 3) investigate theinfluence of capping material quality on success of mine waste revegetation to enhance cap and plantremediation technology; 4) model exposures to mining waste contaminants accounting for socio-demographicsto understand risk factors that drive development of diabetes; 5) mitigate the human impacts of exposure tomining waste through effective interaction with stakeholders including regulators the mining industry andaffected communities; 6) serve as a global resource for human and environmental health issues associated withmetal mining; and 7) train and graduate professionals who are equipped to address complex 21st centuryenvironmental hazardous waste problems (Aim 7). The expected outcome of this UA SRP effort is a measurablereduction in diabetes (and other diseases) in mining communities and perhaps beyond.