Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics (VICE-MPRINT)

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PROJECT SUMMARY / ABSTRACT - OVERALL There is a rapidly expanding knowledge base enabling precision therapeutics for a number of human diseases, but there are significant unmet needs in evidence generation to support translation to the treatment of children and pregnant/post-partum women. The recent widespread adoption of electronic health records (EHRs) and the linkage of these data to other large datasets represents an unprecedented opportunity for clinical research and discovery. The goals of this Center of Excellence in Maternal and Pediatric Precision Therapeutics are: to address key knowledge gaps and perform clinical research in pharmacogenomics and neonatal opioid withdrawal syndrome; to leverage data science methodologies and develop novel tools that support maternal and pediatric precision therapeutics research; and to enhance training for maternal and pediatric precision therapeutics at the local, regional, and national levels. We bring to this effort a unique collection of investigators, institutional support, tools, and resources that enable a paradigm-shift from current norms of slow, incremental progress. Project 1 will: use a community engaged approach to illuminate knowledge of, attitudes about, and priorities for pharmacogenomics; validate pharmacogenomic associations for maternal and pediatric populations using the innovative and generalizable strategy of EHR phenotyping; and identify and quantify variants with unknown functional consequence in diverse individuals to inform future research efforts and reduce disparities. Project 2 will: develop and validate EHR-based algorithms to identify a cohort of opioid- exposed infants and their mothers (dyads) and create a novel linkage of these data to state-wide data; test the hypothesis that use of medications for opioid use disorder is associated with improved early outcomes; and test the hypothesis that opioid use disorder treatment is associated with improvements in the novel longitudinal outcome of dyadic stability. These projects are led by multidisciplinary teams that include Investigators in Pediatrics and Obstetrics, and who are nationally recognized leaders in their respective fields. Both Projects will be supported by a Scientific Core – the Phenotyping Support Core - which enhances each project with expert phenotyping, machine learning/artificial intelligence, and experience in generalizing and disseminating phenotyping approaches. An Administrative Core will provide logistical support for the Center, supervise training opportunities, and ensure scientific interchange within the CET and with the MPRINT Hub. This work will contribute to innovative approaches to precision therapeutics for mothers and children and will develop the educational infrastructure to support the training of physician-scientists to support further advances well into the future.