Life-course, exposomics, and analytic program (LEAP) in Women's Health K12

PROJECT SUMMARY Advancing personalized medicine requires the study of women's health encompassing female-specific condi- tions, such as adverse reproductive outcomes, endometriosis, menopause and gynecological cancers, as well as disorders that clearly differ in prevalence, etiology and natural history between sexes, such as chronic respir- atory disease, cardiometabolic disease, and neuropsychiatric disorders. The underlying pathogenesis of multi- factorial disorders with variable onset across the lifespan reflect development-specific exposures/experiences, at both the individual- and broader community-level, and individual response to these factors. Programming of health outcomes results from environment-induced shifts in a host of integrated molecular, cellular, and physio- logical states against a genetic background with innumerable social and chemical, nutritional, and microbial exposures modulating these mechanisms. Moreover, sex-specific biology further modulate disease trajectories over the lifespan. Given the cross-disciplinary contributing factors, addressing women's health will require transdisciplinary (TD) team-based science training that integrates and extends beyond discipline-specific concepts, approaches, and methods. Life course science underscores the relative importance of exposures dur- ing different life stages in relation to health, with exposure(s) within vulnerable windows having more significant and lasting effects on health than those outside these windows. Although much focus has been on the in utero and early childhood periods in disease programming, other life stages including adolescence (puberty), pregnancy, and the menopause transition, need to be considered as vulnerable windows during which future women's health potential is programmed or shifted. These complexities underscore the need to conduct studies addressing both susceptibility windows and the importance of coincident exposures to elucidate disease mani- festations. The exposome concept addresses such complexities as it frames the study of the effects of all health- relevant environmental factors over the life course using both targeted and untargeted (omics-scale) discovery approaches. In light of the institutional investments, established infrastructure and resources, as well as men- tored training track record summarized herein, Mount Sinai Life-course, Exposomics, and Analytic Program (LEAP) in Women's Health K12 is uniquely poised to constitute a unique training ecosystem for women's health scholars focused on developing transdisciplinary (TD) competencies and foundational principles in life course theory, exposure science and environmental epidemiology, and data science - all key components of exposomics - to address current research and training gaps in women's health. Proposed initiatives will be facilitated through the LEAP Core with centralized resources and scientific expertise that establishes a knowledge base serving to accelerate training in cutting-edge research that more comprehensibly considers environmental influences on women's health across the life-course.