ABSTRACT (Overall) This is a competing renewal application for the Environmental Health Sciences Core Center at the University of Michigan, submitted in the final year of our second term of support. Our Center is organized around the theme of critical windows of susceptibility to environmental exposures as important determinants of disease, forming the Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD). Lifestage, as used in this application, refers to clinically-recognized stages of development, mid-life, and aging that pertain to the pre- conception, prenatal, infant, child, adolescent, reproductive age adult, and aging adult periods. Our Center builds on a strong foundation of research activity and support in environmental health sciences, with 22 NIEHS grants and projects, including Outstanding New Environmental Health Scientist (ONES) and Revolutionizing Innovative, Visionary Environmental health Research (RIVER) awards and participation in Superfund and other NIEHS programs. The M-LEEaD mission is to accelerate research that defines impacts of environmental exposures during vulnerable life stages and to promote translation of findings to improve clinical and public health interventions for the mitigation of disease. Our Center implements its mission through infrastructural support of established and new investigators applying novel transdisciplinary approaches that increase understanding of how exposures target vulnerable stages of life. Support for research is provided through integrated Center programs that include a Pilot Project Program, three Facility Cores, and three Research Teams to enhance translation of research findings into applications for patients and communities to support a comprehensive and integrated environmental health paradigm. Facility Cores are: Integrated Health Sciences (IHS); Exposure Assessment (EA); and Pan-Omics and Data Science (PODS). Research Teams are organized around translational impact: Cumulative Exposures & Population Health; Climate Change & Health Disparities; and Toxicological Mechanisms & Health Outcomes. Research is coupled with engagement of stakeholder communities through the Community Engagement Core (CEC), and training of future leaders through our Career Development Program. An Administrative Core oversees the functioning of the Center. M-LEEaD strives to accomplish its mission through four specific aims: 1) Integrate institutional programs and facilities to provide structure and resources that accelerate understanding of complex relationships among environmental exposures, human biology, and disease; 2) Foster integration and cooperation among investigators across traditional and emerging disciplines to conduct research that translates to improved strategies to prevent environmentally-induced disorders; 3) Build programmatic and scientific capacity through support for scientists at critical career stages to engage in research that addresses critical questions in enviro...