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

人类胎盘表观/基因组与胎儿生长相关的综合分析

• 批准号: 9883823
• 负责人: Corina Lesseur Perez
• 金额: $ 11.88万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883823
• 关键词: Accounting; Address; Adult; Affect; Big Data; Bioinformatics; Biological; Biological Markers; Birth; Birth Weight; Blood specimen; Catalogs; Cells; Child Health; Cohort Studies; Complex; Computational Biology; DNA; DNA Methylation; Data; Development; Disease; Elderly; Environment; Epidemiologist; Epidemiology; Expression Profiling; Face; Faculty; Fetal Growth; Fetal health; Foundations; Funding; Future; Gene Expression; Genetic Fingerprintings; Genome; Genomics; Genotype; Goals; Health; Heterogeneity; Human; Individual; Individual Differences; Inherited; Knowledge; Lasers; Life; Link; Longevity; Malignant Neoplasms; Maternal Health; Mentors; Mesenchymal; Methods; Methylation; Molecular; Molecular Epidemiology; Multiomic Data; Outcome; Pathology; Phenotype; Placenta; Placental Biology; Population Study; Positioning Attribute; Proxy; Research; Research Personnel; Research Training; Resources; Rhode Island; Risk; Sampling; Scientist; Secure; Single Nucleotide Polymorphism; Syncytiotrophoblast; Tissue Sample; Tissues; Training; Translating; Work; base; career; cell type; cohort; computer science; cost effective; cytotrophoblast; disorder prevention; disorder risk; early life exposure; empowered; epidemiologic data; epidemiology study; experience; fetal; fetal programming; genome sciences; genome wide association study; genome-wide; genome-wide analysis; genomic data; genomic locus; genomic profiles; improved; in utero; insight; interest; methylome; molecular subtypes; multiple omics; next generation; offspring; population based; research study; skills; tenure track; trait; transcriptome; trophoblast

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.

项目摘要 我是一名分子流行病学家，主要研究兴趣是了解个体间的差异， 疾病风险以及早期暴露如何影响这些差异。本提案的目的是 接受培训，并获得所需的技能，通过整合多尺度继续我的学术生涯 表观/基因组胎盘分子特征，并将其与胎儿生长联系起来，以提供对胎儿生长机制的深入了解 胎盘对健康和疾病的发育起源（DOHaD）的贡献。 在本提案中，我计划与具有跨学科专业知识的专家指导团队一起进行培训， 综合基因组学和生物信息学、早期流行病学以及胎盘生物学和病理学。的 我建议正式的课程和培训与我的导师博士柯浩，陈佳，卡门Marsit和博士。 哈维克里曼，将使我获得必要的知识和技能，成为一个独立的 跨学科研究员这次培训将使我能够实现我的长期职业目标， 早期生命分子流行病学家，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，从一个完善的 出生队列，罗得岛出生队列研究。具体来说，我将1）在先进的整合基因组学培训 和计算机科学方法，2）与Jia Chen博士一起培训早期生命分子流行病学 和卡门·马西特，3）与哈维·克里曼博士一起接受胎盘生物学和病理学培训，以描述 胎盘细胞亚群的epi/基因组学，4）融合整合基因组学研究，胎盘 病理学和早期生命分子流行病学，成为一个跨学科的科学家5）翻译 研究和培训，以定位自己作为一个独立的调查员与终身教职职位， 可以使用R 01。 这项拟议的研究和培训将解决以下知识差距：1）该提案代表了 首次对胎盘DNA甲基化、转录组及其 与胎儿基因型相互作用和2）计划构建胎盘细胞亚群表位/基因组参照 可以在未来的研究中加以利用。通过这项研究获得的知识有可能 更广泛地宣传宫内环境对整个生命周期健康的影响。我会 通过从以前资助的队列中勒韦林可用资源，以具有成本效益的方式开展这项研究。 最后，本文的研究和提出的培训打算为我成为一名独立的人奠定了基础 一位旨在揭示DOHaD分子特征的研究人员，在未来的研究中， 生物标志物来预防疾病。