Prenatal PM2.5 and programming of respiratory outcomes: Placental biomarkers and effect modification by stress

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Project Summary I am a physician-scientist with a primary research interest in the programming of respiratory diseases by prenatal/early-life environmental exposures, such as air pollution and maternal stress, with particular interest in the programming mechanisms at the maternal-fetal interface, i.e., the placenta. With research linking ambient air pollution to childhood respiratory disease, the goal of this proposal is to add to the growing research linking urban air pollutants, stress, and respiratory development by identifying sensitive windows of exposure and identifying novel mitochondrial and telomere biomarkers through which in utero exposures may be operating to impact future respiratory development. Through formal coursework and expert mentoring, this award will enable me to develop the knowledge and skills necessary to become an independent transdisciplinary environmental health scientist and achieve my long-term career goals: to establish a competitive and successfully funded program to study the cumulative effects of environmental exposures (e.g., air pollution/stress) on the programming of biological mechanisms related to chronic childhood conditions. While this award focuses on respiratory outcomes, it is worth noting that the knowledge and skills obtained will be broadly applicable to a range of child health outcomes given the large number of childhood conditions with mitochondrial and telomere underpinnings (e.g., asthma, obesity, cardiovascular disease, neurocognitive outcomes). Specifically, I will 1) obtain training in air pollution and stress assessment in the context of a longitudinal cohort study design; 2) receive training and guidance in selecting and interpreting mitochondrial and telomere analyses; and 3) undergo extensive training in advanced quantitative methods (e.g. non-linear distributed lag models) to understand dose-response and temporal relationships between air pollution and health. The proposed study will be the first to investigate windows of vulnerability to prenatal ambient air pollution exposure on child respiratory development and to investigate mitochondrial and telomere biomarkers in a target tissue (e.g. placenta) with respect to prenatal environmental exposures (e.g. ambient air pollution and stress) and early respiratory phenotypes. We will use daily air pollution exposures derived from a validated spatio-temporal modeling approach coupled with distributed lag methods to identify sensitive windows of air pollution exposure on respiratory phenotype. We will use state-of-art analyses of placental mitochondrial and telomere biomarkers that: 1) have been shown to be altered by environmental exposures; and 2) reflect cumulative oxidative damage over gestation. This study is also highly cost effective as we will leverage the resources of an existing well-phenotyped urban and ethnically-mixed pregnancy cohort [Perinatal Environmental and Development Study (PEDS)] with extant environmental exposure (air pollution and stress), covariate, and epigenome data.