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.

该方案的目标是整合多尺度表观/基因组胎盘分子特征并将其联系起来 为了解胎盘对胎儿发育的贡献提供机制洞察 健康与疾病的起源(DOHAD)。我是一名分子流行病学家，主要研究兴趣 了解疾病风险的个体间差异以及早期接触如何影响 这些差异。在K99阶段，我接受了综合基因组学和生物信息学的早期培训 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， 陈佳，卡门·马西特和哈维·克利曼博士。本研究的目的是：1)构建一个 完整的足月胎盘表观/基因组目录；2)细胞类型特异性DNA甲基组的特征 和转录组，以构建人足月胎盘的细胞类型参考板和3)评估 胎盘分子特征对新生儿出生体重的影响在这个提案中，我利用现有的表观/基因组 以及罗德岛出生队列研究和特定胎盘细胞类型的流行病学数据 EPI/基因组学图谱，首要目标是定位与分娩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提供更广泛的信息 宫内环境对人一生健康及胎盘发育的影响 为疾病预防提供信息的生物标志物。