Prenatal air pollution, DNA methylation and early signs of atherosclerosis

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DESCRIPTION (provided by applicant) Dr. Carrie Breton received her Sc.D. in epidemiology in 2007 from the Harvard School of Public Health and is currently an Assistant Professor in the Department of Preventive Medicine at the University of Southern California where she is part of a highly interactive environmental health group headed by Dr. Frank Gilliland. The goal of the proposed five-year career development award is to provide Dr. Breton with the knowledge and necessary skills to become an independent researcher. A integrated approach comprised of a research project, clinic and laboratory rotations, informal and structured coursework, seminars, and mentoring has been designed to accomplish the following specific goals: 1) develop a comprehensive knowledge base in clinical cardiovascular epidemiology, with a focus on markers of cardiovascular disease that may be present in children, and 2) master the emerging statistical/bioinformatics techniques necessary for properly analyzing and synthesizing epigenetic data. Three highly qualified and experienced mentors will supervise her training. Dr. Gilliland (environmental epidemiology) will serve as the primary mentor, while Drs. Howard Hodis (Atherosclerosis Research Unit) and Kim Siegmund (bioinformatics for epigenetics) will serve as respective co- mentors. The scientific culture and collaborative research atmosphere both in the Department and in the University provide an ideal environment for the candidate's academic career development. The objective of Dr. Breton's research project is to understand the relationship between prenatal particulate matter and traffic exposures, atherosclerosis and the role of DNA methylation in newborn blood. Specifically, the project pursues the hypotheses that 1) prenatal exposures to PM2.5 and traffic-related pollutants promote atherogenesis, and that differences in these exposures lead to differences in carotid artery thickness (IMT) and stiffness measured in children; 2) the effects of prenatal air pollution exposures on IMT/stiffness are mediated through differences in DNA methylation, such that levels of DNA methylation in repetitive elements and in individual CpG loci in newborn blood are associated with IMT/stiffness in children and prenatal exposure to air pollution alters these levels of DNA methylation. These hypotheses will be investigated using the wealth of health and exposure data available in a subset of the Children's Health Study, an ongoing cohort study of 11,000 children investigating both genetic and environmental factors related to respiratory disease. The unique feature of the proposed study is the integration of a large children's population-based study, cutting edge epigenomic resources, use of dried newborn blood spots, and an extensive air pollution monitoring network with exposure information from birth forward. The results from this research will contribute to the rapidly evolving field of environmental epigenomics by investigating novel associations between air pollutants, DNA methylation, and early life atherogenesis. Moreover, small differences in IMT and stiffness at a young age may translate into clinically relevant cardiovascular disease later in life - a leading cause of morbidity and mortality in the U.S.