(Biological Responses Indicators Resource) Emerging applications of targeted epigenetic and genetic as well as high-dimensional epigenomic and genomic data in environmental health sciences offer an unparalleled opportunity to disentangle the effects of early life exposures on child health outcomes that presage adult chronic diseases. For example, metabolic syndrome affects ~25% of the U.S. adults and as many as 30% of obese adolescents: understanding how exposures to mixtures of metals (Pb, Cd) and endocrine disrupting chemicals (e.g., BPA, phthalates) during pregnancy and adolescence stimulate biological responses to lead to metabolic dysregulation is highly relevant to clinical and public health practice. The Biological Responses Indicators Resource (BRIR) of the University of Michigan (U of M) Children?s Health Exposure Analysis Resource (M-CHEAR) Laboratory Hub will provide external investigators with sensitive, selective, and state-of-the-art assessments of functional measures of individual response to environmental stressors that can be effectively applied to epidemiological and clinical studies of children?s health. This will be done by 1) leveraging methods that we and Cores at the University of Michigan (U of M) have already developed, 2) offering our unique content expertise in epigenetic, epigenomic, and genomic analysis, 3) providing application and interpretation of well-validated assays for measuring biological response indicators, 4) implementing strict quality assurance/quality control processes, and 5) continually expanding our analysis capabilities. To avoid overlap with services offered by the M-CHEAR Targeted Analysis Resource (hormone & stress markers, inflammation & immune response markers, and general oxidative stress), the BRIR will focus on functional epigenetic, epigenomic, genetic, and genomic molecular assays, including proteomics, oxidative stress, metabolic response, immune response, psychosocial stress, and DNA damage and repair pathways. In addition to the world-class laboratory facilities located at U of M and its partnering laboratory (NSF International), M-CHEAR leadership also possesses unique expertise and experience to offer external researchers, including experience leading and participating in other large center grants and vast content expertise in exposure science, environmental epidemiology, molecular biology, child growth and development, human nutrition, metabolomics, epigenomics, analytical chemistry, biostatistics/bioinformatics, and the study of biomarker development, validation, and utility.