The Columbia Northern Plains SRP is a new partnership that has five Projects and four Cores and will use systems science, local knowledge, and innovative technology through the following aims: (1) Develop household-level spatial and temporal models of groundwater metal concentrations integrating new measures of water As, U, and redox parameters with USGS and IHS data. (2) Trace sources and cycling of metals in water and biological specimens through stable isotope measurements (U, Se) to reveal redox state and inform on local and distal sources of contamination, directly addressing our communities’ concern. (3) Determine latent and concurrent cardiometabolic effects of As and U in humans (Strong Heart As/U Lifelong study, SHAUL), and in humanrelevant mouse models. (4) Integrate molecular mechanisms of As and U toxicity using multi-omics (epigenomics, metabolomics) in longitudinal studies in humans (SHAUL) and mice. (5) Develop sustainable interventions using lightbased, point-of-use water remediation technology for As/U.