Integrative analysis of human placental epi/genome in relation to fetal growth

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PROJECT SUMMARY I am a molecular epidemiologist with a primary research interest in understanding inter-individual differences in disease risk and how early-life exposures can influence these differences. The goal of this proposal is to receive training and to the acquire the skills needed to continue my academic career by integrating multi-scale epi/genomic placental molecular features and relate this to fetal growth to provide mechanism insight into the contribution of the placenta to the developmental Developmental Origins of Health and Disease (DOHaD). In this proposal, I plan to train with and expert mentoring team with transdisciplinary expertise covering, integrative genomics and bioinformatics, early-life epidemiology, and placental biology and pathology. The proposed formal coursework and training with my mentors Drs. Ke Hao, Jia Chen, Carmen Marsit and Dr. Harvey Kliman, will enable me to acquire the knowledge and skills necessary to become an independent transdisciplinary researcher. This training will enable me to achieve my long-term career goal of becoming and early-life molecular epidemiologist that can leverage and integrate multi-omics data from population studies. To this end, herein, I propose to leverage existent epi/genomic and epidemiological data from a well-stablished birth cohort, the Rhode Island Birth Cohort Study. Specifically I will 1) train in advanced integrative genomics and computer science methods with Dr. Ke Hao, 2) train early-life molecular epidemiology with Drs. Jia Chen and Carmen Marsit, 3) train in placental biology and pathology with Dr. Harvey Kliman to characterize the epi/genomic of placental cell subpopulations, 4) amalgamate research on integrative genomics, placental pathology and early-life molecular epidemiology to become an interdisciplinary scientist 5) translate the research and training to position myself as an independent investigator with a tenure track faculty position and able to secure an R01. This proposed research and training will address the following knowledge gaps: 1) the proposal represents the first comprehensive and integrated genome-wide study of placental DNA methylation, transcriptome and their interplay with fetal genotypes and 2) plan to construct a placental cell-subpopulation epi/genomic reference that can be leveraged in future studies. The knowledge gained through this research study has the potential to inform more broadly on the influence of the intrauterine environment on health throughout the lifespan. I will conduct this study in a cost-effective manner by levering available resources from a previously funded cohort. Finally, this study and proposed training intends to lay the foundation for me to become an independent researcher that aims to uncover molecular features involved in DOHaD and in future studies develop placental biomarkers to inform disease prevention.