Integrating the Exposome into Longitudinal Multiomics Profiling

项目摘要/摘要 以下是索菲亚·米里亚姆·舍斯勒-菲奥伦扎·罗斯医学、博士、物理医学和医学博士的K08奖项申请表 拥有脊髓损伤医学专业证书的康复医生和人群健康科学家。 她的长期目标是领导一个多学科研究团队，能够应用复杂的系统方法和其他新颖的方法 分析方法解决不良暴露对神经康复和长期健康的影响 神经创伤及相关疾病。 这一K08奖项将为Rose博士提供必要的支持，以实现以下教育目标。 1.发展评估环境、心理社会和内部暴露的专门知识。2.培养评估方面的专业知识 利用纵向多组学分析研究暴露的生物学效应。3.在纵向发展高级技能 多组学数据分析、复杂系统和因果建模方法。4.培养领导多学科的技能 研究团队。5.培养翻译技能并设计一项研究，以在临床上验证研究的一些发现 或以人口为基础的样本，这将成为她独立研究生涯的起点。 为了实现这些目标，Rose博士组建了一个由以下专家组成的指导团队：Michael Snyder博士 (主要导师)是个性化医疗领域的领导者，他已经建立了一个独特的队列 全面的，最先进的，多组学分析，与频繁的纵向采样。他提供了接触这个有钱人的途径 为新的分析提供数据存储库和实验室支持。马克·卡伦博士是斯坦福大学研究中心主任 人口健康科学和斯坦福种族和种族公平精确健康中心的领导人，该中心专注于 使用精准医疗工具改善服务不足的族裔和种族群体的健康。卡伦博士带来了可观的 整合关于有毒物质暴露、心理社会暴露和行为测量的数据以了解如何 暴露的不同方面共同作用，产生积极和消极的结果。David Rehkopf博士是一位 精通生命周期流行病学和先进的纵向、非线性和空间数据分析方法。马克博士 费尔德曼是复杂系统和数学生物学方面的专家，他在数量文化进化方面的工作结合了 来自多个学科的工具，以了解文化和基因在塑造人类进化中的组合作用。Dr。 乔治·斯拉维奇是压力评估、社会基因组学和心理神经免疫学方面的专家。 具体目标如下：目标1.增加对持久性有机化学品(POCs)的靶向测定，作为POC的一种衡量标准 暴露在研究中，并描述与内部暴露、逆境和压力暴露的关系。目标2.评估 POC的纵向轨迹及其与临床和组学指标的协变性。目标3.纵向整合 多组学数据和多扰动数据创建复杂系统-因果网络模型来评估关节 POCs和其他暴露对受损的血糖调节的影响。

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.