Exposomic Approach to Identifying WTC Exposures and Effects in Survivor Youth.

PROJECT SUMMARY Pregnant women and children who lived, worked or attended school near the World Trade Center (WTC) on September 11, 2001 experienced a variety of psychological and chemical exposures with potential adverse consequences for later health and development. In contrast to psychological effects, physical health effects of early life exposure to the World Trade Center (WTC) disaster remain poorly understood. This is particularly important as the well-known developmental origins of health and disease (DoHAD) concept indicates that exposures occurring during sensitive developmental windows may lead to adverse health outcomes in later life. We have recently demonstrated that neonates and children exposed to chemicals (e.g., dioxins, perfluoroalkylsubstances (PFAS)) known to be associated with WTC experience adverse health outcomes including adverse birth outcomes, altered lipid levels, and asthma. However, characterizing the totality of WTC exposure—including both psychologicial and chemical exposures—has been challenging, limiting our ability to identify WTC-related health effects, which are likely to emerge as exposed children age. Here, we employ advances in molecular laboratory technology, which have enabled high-resolution methods to measure thousands of exogenous chemicals and their endogenous biological responses to these exposures. These powerful exposomic and metabolomic approaches have been used to enhance disease prognosis and diagnosis as well as provide insight into disease pathogenesis in neonates, children and adults. Using two cohorts of WTC- exposed neonates and youth, we can 1) identify an exogenous chemical signature that is associated with conventional WTC exposure measures including proximity-based exposure metrics and targeted biomarkers associated WTC exposure indices (Aim 1); 2) identify a metabolomic signature that reflects the biological response to both conventional WTC exposure measures and psychological stressors associated with WTC exposure (Aim 2); and 3) determine if WTC-exposure related exogenous chemical signatures (Aim 3a) and metabolomic signatures (Aim 3b) are associated with adverse health outcomes in children. If confirmed, the exogenous chemical and metabolomic signatures we identify in blood stored from these two vulnerable WTC- exposed populations will provide unique fingerprints that can be used to predict adverse WTC-related outcomes that may emerge as exposed children age into adulthood.