for Overall Center The University of Arizona Superfund Research Center addresses the unique human health risks encountered in the U.S. Southwest, a region with a rich history of metal mining and generation of mine wastes. We (and others) have demonstrated how mining communities in this region experience layers of exposure to hazardous metals and metal(loid)s. These layers of exposure include drinking water, but uniquely in this environment, substantial exposure occurs from inhalation and ingestion of metal(loid)-contaminated mine waste dusts transported into homes and exterior environments including soils, gardens, and play areas. An added layer is that these populations are simultaneously subjected to extensive, continuous inhalation exposure to fungal spores. Little information exists on the risks associated with inhalation exposure to metal(loid)-contaminated dusts, let alone risks from co-exposure to metals and fungal spores. Yet the outcomes of inflammation-related lung injury following inhalation exposures are serious, ranging from asthma to fibrosis, chronic obstructive pulmonary disease, and cancer. Our overall goal is to construct a mechanistic model of how chronic exposure to mining-impacted dust that is co-contaminated with metal(loid)s and fungal spores contributes to the development of nonmalignant lung diseases, then implement this model to predict exposures and associated health outcomes, to inform public health prevention in communities neighboring mine waste sites and design remediation-based interventions to exposure. To achieve this goal, we have four highly integrated research projects and four cores that will work to measurably reduce non-malignant lung diseases in Superfund mining communities and beyond. To this end, we will: 1) characterize how inhalation exposure to metal(loid)- containing mine waste particulates lead to lung tissue injury, including compromised mucociliary clearance and epithelial barrier function, tissue disrepair, and fibr