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

胎盘和母乳 microRNA 与生命早期生长和代谢的关系

• 批准号: 10390485
• 负责人: Elizabeth Marie Kennedy Goehring
• 金额: $ 13.1万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-09 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390485
• 关键词: 3' Untranslated Regions; Address; Advisory Committees; Affect; Automobile Driving; Base Pairing; Bioinformatics; Biological Markers; Biology; Birth; Body mass index; Breast Feeding; Breastfed infant; Cardiovascular Diseases; Child; Child Health; Childhood; Code; Cohort Studies; DNA; DNA Methylation; Data; Development; Disease; Educational Status; Epidemiologic Methods; Epidemiologist; Epidemiology; Epigenetic Process; Extracellular Matrix; Faculty; Fetal Growth; Future; Gene Expression; Genes; Genetic; Genetic Research; Genetic Transcription; Genomics; Genotype; Goals; Growth; Health; Home; Human Genetics; Human Milk; Infant; Intestines; Knowledge; Life; Measures; Mediating; Mediator of activation protein; Mentors; Mentorship; Messenger RNA; Metabolic; Metabolic Diseases; Metabolism; Methods; MicroRNAs; Molecular; Molecular Epidemiology; National Institute of Child Health and Human Development; New Hampshire; Obesity; Outcome; Pattern; Phase; Placenta; Placental Biology; Population; Population Study; Positioning Attribute; Pregnancy; Proteins; Public Health Schools; Quantitative Trait Loci; Recommendation; Regulator Genes; Research; Research Design; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Rhode Island; Role; Secure; Stimulus; Testing; Tissues; Training; Transcript; Universities; Untranslated RNA; Variant; Work; base; career; cohort; disorder prevention; early childhood; early life exposure; empowered; epidemiology study; experience; extracellular; follow-up; genetic variant; genome-wide; gestational weight gain; high risk; improved; insight; interest; multiple omics; next generation; nutrition; obese mothers; obesity in children; obesity risk; offspring; population based; prepregnancy; research study; response; skills; tenure track; transcriptome; transcriptomics

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.

项目概要 本提案中概述的工作旨在提供开始我的工作所需的培训和技能 作为分子流行病学家的独立学术生涯，能够获得终身教授职位 以及我自己的研究支持。我的博士研究重点是 DNA 的机械关系 甲基化和基因转录，为更多的分析和解释铺平了道路 对妊娠暴露的分子机制进行复杂的群体研究。我的 经验使我的主要研究兴趣是生命早期的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，该项目整合了遗传、 表观遗传学和转录组学措施评估胎盘和母乳介导的暴露的作用 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；和微小RNA生物学。我将接受个性化培训 我的共同导师是分子流行病学专家 Carmen Marsit 博士，以及分子流行病学专家 Usha Ramakrishnan 博士。 儿童生长与营养专家。我将从跨学科咨询中获得额外指导 委员会由博士组成。玛格丽特·卡拉加斯、迈克尔·爱泼斯坦和斯科特·朗之万。这个团队有专业知识 综合基因组学、生物信息学、统计遗传学、早期流行病学和 microRNA 生物学。 埃默里大学是罗林斯公共卫生学院的所在地，该学院在美国排名第 5，并且在以下领域拥有世界领先水平： 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 使我能够实现成为一名独立的早期分子分子的长期职业目标 流行病学家能够获得终身教授职位和我自己的研究支持。 这里提出的研究将解决以下知识空白：1）胎盘的作用 microRNA 在儿童早期生长和代谢中的作用； 2) 其背后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 的作用 母亲代谢状态的中介因素影响幼儿代谢状态。我的研究将提供 深入了解妊娠和早期生命暴露对早期生长和发育的影响 代谢状态。更广泛地说，通过这项研究获得的知识有可能 对 microRNA 生物学、胎盘生物学、肥胖症以及健康和发育起源做出贡献 疾病（DOHaD）。最后，我提议的培训和研究将为我的独立研究做好准备 在我的职业生涯中，我利用人口研究中最先进的“组学”方法来评估分子生物学 儿童健康的基础机制并开发为疾病提供建议的生物标志物 预防。

项目成果

Maternal depression and adverse neighbourhood conditions during pregnancy are associated with gestational epigenetic age deceleration.

怀孕期间母亲的抑郁和不良的邻里条件与表观遗传胎龄减慢有关。

• 发表时间: 2022-12
• 影响因子: 3.7
• 作者: Appleton, Allison A;Lin, Betty;Kennedy, Elizabeth M;Holdsworth, Elizabeth A
• 通讯作者: Holdsworth, Elizabeth A