Placental and breastmilk microRNAs in relation to early-life growth and metabolism

项目摘要 本建议书中概述的工作旨在提供开始我的 作为一名分子流行病学家的独立学术生涯，能够获得终身教职 和我自己的研究支持我的博士研究集中在DNA的机械关系 甲基化和基因转录，这为分析和解释更多的 妊娠期暴露分子机制的复杂人群研究。我 经验导致我的主要研究兴趣是早期生活暴露如何影响儿童的健康。我会 通过培训，指导和严格的研究项目来实现我的目标， 评估胎盘和母乳介导的暴露在 与生命早期的生长和新陈代谢有关。 通过我的研究和培训计划，我将获得流行病学方法和研究方面的专业知识 设计;儿童生长，营养和肥胖;和microRNA生物学。我将接受个性化的培训， 我的共同导师，卡门·马西特博士，分子流行病学专家，和乌莎·拉马克里希南博士， 儿童生长和营养专家。我将从一个跨学科顾问那里得到额外的指导 委员会由Margaret Karagas博士，Michael Epstein和Scott Langevin组成。这个团队有专业知识 在整合基因组学、生物信息学、统计遗传学、早期生命流行病学和microRNA生物学方面。 埃默里大学是罗林斯公共卫生学院的所在地，在美国排名第五，也是世界领先的公共卫生机构。 流行病学和人类遗传学研究。我将在这里接受的正式培训和专家指导将 使我能够实现我的长期职业目标，成为一个独立的， 流行病学家能够确保终身教职和我自己的研究支持。 本文提出的研究将解决以下知识空白：1）胎盘的作用 儿童早期生长和代谢中的microRNA; 2）作为儿童早期生长和代谢基础的遗传和表观遗传动力学 胎盘中的microRNA表达; 3）胎盘和细胞外母乳microRNA作为 母亲代谢状态的介质影响幼儿的代谢状态。我的研究将提供 深入了解妊娠期和早期生活暴露对早期生长发育的影响， 代谢状态更广泛地说，通过这项研究获得的知识有可能 有助于microRNA生物学，胎盘生物学，肥胖和健康的发育起源， 疾病（DOHaD）。最后，我建议的培训和研究将为我独立研究做好准备 职业生涯中，我利用人口研究中的尖端`组学方法来评估分子 儿童健康的基础机制，并开发生物标志物，为疾病提供建议 预防

Project Summary The work outlined in this proposal is meant to provide the training and skills necessary to begin my independent academic career as a molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. My doctoral research focused on the mechanistic relationship of DNA methylation and gene transcription, which paved the way for the analysis and interpretation of more complicated population studies of the molecular mechanisms that underlie gestational exposures. My experience has led to my primary research interest in how early-life exposures influence children's health. I will accomplish my goals through training, mentorship and a rigorous research project that integrates genetic, epigenetic and transcriptomic measures to assess the role of placenta- and breastmilk-mediated exposures in relation to early-life growth and metabolism. Through my research and training plan, I will gain expertise in epidemiologic methods and study design; childhood growth, nutrition and obesity; and microRNA biology. I will receive personalized training from my co-mentors, Dr. Carmen Marsit, an expert in molecular epidemiology, and Dr. Usha Ramakrishnan, an expert in children's growth and nutrition. I will receive additional guidance from a transdisciplinary advisory committee composed of Drs. Margaret Karagas, Michael Epstein, and Scott Langevin. This team has expertise in integrative genomics, bioinformatics, statistical genetics, early-life epidemiology and microRNA biology. Emory University is home to Rollins School of Public Health, ranked 5th in the US, as well as to world leaders in epidemiology and human genetics research. The formal training and expert guidance I will receive here will enable me to achieve my long-term career goal of becoming an independent, early-life molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. The research proposed here will address the following gaps in knowledge: 1) the role of placental microRNAs in early-childhood growth and metabolism; 2) the genetic and epigenetic dynamics that underlie microRNA expression in placenta; and 3) the role of placental and extracellular breastmilk microRNAs as mediators of maternal metabolic status influence on early childhood metabolic status. My research will provide insight into the contribution of gestational and early-life exposures in the development of early growth and metabolic status. More broadly, the knowledge gained through this research study has the potential to contribute to microRNA biology, placental biology, obesity and to the Developmental Origins of Health and Disease (DOHaD). Finally, my proposed training and research will prepare me for an independent research career, in which I utilize cutting-edge `omics methods in population-studies to assess the molecular mechanisms that underlie children's health and develop biomarkers that inform recommendations for disease prevention.