Integrating the Exposome into Longitudinal Multiomics Profiling

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PROJECT SUMMARY/ABSTRACT This is an application for a K08 award for Sophia Miryam Schüssler-Fiorenza Rose, MD, PhD, a Physical Medicine and Rehabilitation physician with subspecialty certification in Spinal Cord Injury Medicine and a Population Health Scientist. Her long-term goal is to lead a multidisciplinary research team that can apply complex systems approaches and other novel analytic methods to address the effects of adverse exposures on neurorecovery and long term health in those affected by neurotrauma and related diseases. This K08 award will provide Dr. Rose the support necessary to accomplish the following educational goals. 1. Develop expertise assessing the environmental, psychosocial and internal exposome. 2. Develop expertise in assessing biological effects of exposures using longitudinal multiomics profiling. 3. Develop advanced skills in longitudinal multiomics data analysis, complex systems and causal modeling approaches. 4. Develop skills in leading multidisciplinary research teams. 5. Develop translational skills and design a study to validate some of the findings of the research in a clinical or population based sample that will serve as a launching point for her independent research career. To achieve these goals, Dr. Rose has assembled a mentoring team comprised of the following experts: Dr. Michael Snyder (primary mentor) is a leader in the field of personalized medicine who has established a unique cohort undergoing comprehensive, state-of-the-art, multiomics profiling with frequent longitudinal sampling. He provides access to this rich data repository as well as laboratory support for novel analyses. Dr. Mark Cullen is director of the Stanford Center for Population Health Sciences and leader of Stanford Precision Health for Ethnic and Racial Equity Center which focuses on using precision-medicine tools to improve the health of underserved ethnic and racial groups. Dr. Cullen brings considerable experience in integrating data on toxic exposures, psychosocial exposures and behavioral measures to understand how different aspects of the exposome act in combination to produce positive and negative outcomes. Dr. David Rehkopf is an expert in life course epidemiology and advanced longitudinal, nonlinear and spatial data analysis methods. Dr. Marc Feldman is an expert in complex systems and mathematical biology whose work in quantitative cultural evolution combines tools from multiple disciplines to understand the combined roles of culture and genes in shaping human evolution. Dr. George Slavich is an expert in stress assessment, social genomics and psychoneuroimmunology. The specific aims are as follows: Aim 1. Add a targeted assay for persistent organic chemicals (POCs) as a measure of POC exposure to the study and characterize relationship to the internal exposome, adversity and stress exposures. Aim 2. Evaluate the longitudinal trajectories of POCs and their covariation with clinical and omics measures. Aim 3. Integrate longitudinal multiomics data and multiple perturbation data to create a Complex Systems - Causal Network model to evaluate the joint effects of POCs and other exposures on impaired glucose regulation.