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Despite wide adoption of electronic health records (EHRs), a “digital divide” persists between high- and low-resource healthcare settings. However, informatics interventions that specifically target underserved populations can reduce inequities. In this panel, a multidisciplinary group of experts will discuss aspects of a research-practice partnership across multiple federally funded projects that aim to increase the reach and uptake of evidence-based prevention and treatments in underserved populations. Presentations will cover 1) examples of pragmatic clinical trials focused on informatics interventions to increase the uptake of evidence-based prevention and treatments, along with a multisector partnership that supports these implementation studies; 2) rapid-cycle design and adaption of informatics interventions; 3) sociotechnical and EHR adaptation approaches; and 4) population health management approaches. Presenters will cover a broad range of projects, including a study case focused on increasing the uptake of COVID-19 vaccination and testing in underserved communities.