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

项目总结 我是一名分子流行病学家，主要研究兴趣是了解人与人之间的差异。 疾病风险以及早期接触如何影响这些差异。这项提议的目标是 接受培训，并通过整合多尺度来获得继续我的学术生涯所需的技能 EPI/基因组胎盘分子特征及其与胎儿生长的关系，为深入了解胎盘发育机制提供依据 胎盘对健康和疾病的发育起源的贡献(DOHAD) 在这份提案中，我计划与具有跨学科专业知识的专家指导团队一起培训， 综合基因组学和生物信息学、早期生命流行病学、胎盘生物学和病理学。这个 建议与我的导师柯浩博士、陈佳博士、卡门·马西特博士和马西特博士一起进行正式课程和培训。 哈维·克利曼，将使我获得成为独立人士所需的知识和技能 跨学科研究人员。这次培训将使我能够实现我的长期职业目标，成为 早期分子流行病学家，可以利用和整合来自人口研究的多组学数据。 为此，在此，我建议利用现有的表观/基因组和流行病学数据，从一个良好稳定的 出生队列，罗德岛出生队列研究。具体地说，我将培训先进的综合基因组学 和计算机科学方法与柯浩博士合作，2)与贾晨博士一起培训早期生命分子流行病学 和卡门·马西特，在Harvey Kliman博士的指导下接受胎盘生物学和病理学的培训，以确定 胎盘细胞亚群的EPI/基因组学，4)整合基因组学、胎盘 病理学和早期分子流行病学将成为跨学科科学家 研究和培训，将自己定位为一名独立调查员，拥有终身教职和 能够获得一架R01。 这项拟议的研究和培训将解决以下知识差距：1)该提议代表 首次全面和完整的全基因组研究胎盘DNA甲基化、转录组及其 与胎儿基因型的相互作用和2)计划构建胎盘细胞亚群表观/基因组参考 这一点可以在未来的研究中加以利用。通过这项研究性研究获得的知识有可能 更广泛地告知宫内环境对整个生命周期的健康的影响。这就做 通过利用以前资助的队列中的可用资源，以具有成本效益的方式进行这项研究。 最后，这项研究和提出的培训计划，旨在为我成为一名独立的 旨在揭示与DOHaD有关的分子特征并在未来的研究中开发胎盘的研究人员 为疾病预防提供信息的生物标志物。

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.