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: 10611359
• 负责人: Corina Lesseur Perez
• 金额: $ 24.4万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611359
• 关键词: Accounting; Address; Adult; Affect; Big Data; Bioinformatics; Biological; Biological Markers; Birth; Birth Weight; Blood specimen; Catalogs; Cell Separation; Cells; Child Health; Cohort Studies; Complex; Computational Biology; DNA; DNA Methylation; Data; Development; Disease; Elderly; Environment; Epidemiologist; Epidemiology; Face; Fetal Growth; Fetal health; Future; Gene Expression; Genome; Genomics; Genotype; Goals; Health; Heterogeneity; Human; Individual; Individual Differences; Inherited; Knowledge; Lasers; Life; Link; Longevity; Malignant Neoplasms; Maps; Maternal Health; Mentors; Mesenchymal; Methylation; Molecular; Molecular Epidemiology; Outcome; Pathology; Phase; Phenotype; Placenta; Placental Biology; Population Study; Proxy; Research; Research Personnel; Resources; Rhode Island; Sampling; Single Nucleotide Polymorphism; Syncytiotrophoblast; Tissue Sample; Tissues; Training; Work; cell type; cohort; cytotrophoblast; disorder prevention; disorder risk; early life exposure; empowerment; epidemiologic data; epidemiology study; experience; fetal; fetal programming; genome wide association study; genome-wide; genomic data; genomic locus; genomic profiles; improved; in utero; insight; interest; intrauterine environment; methylome; molecular subtypes; multiple omics; next generation; offspring; population based; risk prediction; trait; transcriptome; trophoblast

The goal of this proposal is to integrate 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 Origins of Health and Disease (DOHaD). 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. In the K99 phase, I trained in integrative genomics and bioinformatics, early-life epidemiology, and placental biology and pathology with the help of my mentors and advisors Drs. Ke Hao, Jia Chen, Carmen Marsit and Dr. Harvey Kliman. The aims of this research are: 1) to construct an integrative epi/genomic catalogue of term placentas; 2) to characterize cell-type specific DNA methylome and transcriptome to construct a cell-type reference panel for human term placenta and 3) to evaluate the influence of placental molecular features on birth weight. In this proposal, I leverage existent epi/genomic and epidemiological data from the Rhode Island Birth Cohort Study and placental cell-type specific epi/genomics profiles with the overarching goal of mapping placental molecular features involved in birth weight and DOHaD. The knowledge gained through this research has the potential to inform more broadly on the influence of the intrauterine environment on health throughout the lifespan and develop placental biomarkers to inform disease prevention.

该提案的目标是整合多尺度表型/基因组胎盘分子特征，并将其与 胎儿生长提供机制洞察胎盘的贡献， 健康和疾病的起源（DOHaD）。我是一名分子流行病学家， 了解疾病风险的个体差异以及早期暴露如何影响 这些差异。在K99阶段，我接受了整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，在我的导师和顾问柯浩博士的帮助下， Jia Chen，Carmen Marsit和Harvey Kliman博士。本研究的目的是：1）构建一个 足月胎盘整合表位/基因组目录; 2）表征细胞类型特异性DNA甲基化组 和转录组构建人类足月胎盘的细胞类型参考组，以及3）评估 胎盘分子特征对出生体重的影响在这个提议中，我利用现有的表观/基因组 来自罗得岛出生队列研究的流行病学数据和胎盘细胞类型特异性 EPI/基因组学图谱，其首要目标是绘制与出生有关的胎盘分子特征 体重和DOHaD。通过这项研究获得的知识有可能更广泛地提供信息， 子宫内环境对整个生命周期健康的影响和胎盘发育 生物标志物来预防疾病。