Mitochondrial Markers of Pollution, Stress, and Neurobehavior -
DESCRIPTION (provided by applicant): The candidate is a molecular epidemiologist with primary research interest in the programming mechanisms by which prenatal/early-life exposure to environmental and social pollutants influences the health of children, with particular interest n neurodevelopment. With research linking ambient air pollution and poor neurodevelopment, the goal of this proposal is to add to the growing research linking urban air pollutants, stress and poor neurodevelopment by identifying novel mitochondrial (mt) biomarkers through which in utero exposures may be operating to impact future neurodevelopment. Through formal coursework and expert mentorship by Drs. Rosalind Wright, Andrea Baccarelli, Robert Wright, Michelle Bosquet Enlow, Avraham Reichenberg, Luca Lambertini and Liming Lang, 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 neurobehavioral 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 mt underpinnings (e.g., asthma, obesity, autism, and attention disorders). Specifically, the candidate will 1) undergo extensive laboratory training in Drs. Baccarelli's and Lambertini's laboratories to further enhance my molecular skills; 2) obtain training in measuring and interpreting interactions involving social stressors; and 3) receive guidance and hands-on training in selecting, administering and interpreting neurodevelopmental assessments across early childhood. The proposed study will be the first to investigate complementary mtDNA biomarkers in two target tissues (e.g., placenta and cord blood) with respect to prenatal environmental exposures (e.g., urban air pollutants and stress) and early neurobehavioral phenotypes. The intent is to use state-of-art analyses of mtDNA damage by means of a panel of complementary markers of oxidative damage, heteroplasmy, and mtDNA abundance measured at the maternal-fetal interface (e.g., placenta and cord blood). These markers have properties that make them exceptionally well suited to biomarker development, as they: 1) have been shown to be altered by the environmental exposures; and 2) can mark the presence of damaged mitochondria, a primary source of systemic oxidative stress to which the brain is particularly vulnerable. This study is also highly cost effective as we will leverage the resources
of an existing well-phenotyped urban and ethnically-mixed pregnancy cohort [PRogramming of Intergenerational Stress Mechanisms (PRISM) study] with existing biospecimens and neurobehavioral & environmental data.
