Intrauterine Metal Exposure, Placental Gene Networks and Fetal Growth

项目总结 宫内期间的扰动，包括接触有毒水平的痕量金属，可能会扰乱 适当的胎儿生长和发育，并在整个生命周期内对健康产生不利影响 个人的。胎盘是解释来自宫内环境的信号的主要器官 然而，胎盘转录活性的变化还没有被系统地评估为 可能是胎儿发育异常的介体。全面评估两国之间的相互关系 金属混合物暴露、胎盘基因活性和胎儿生长的可能性随着剂量的增加而变得可行 然而，高维暴露和基因组数据的可用性，充分利用生物 保留在这些大规模数据集中的信息尚未实现。 为了解决这些存在的差距，我们概述了进行环境混合的研究和培训目标 在高通量基因组数据的背景下，在基于人群的研究中建模，并在 生物系统。这项拟议的研究是首次全面整合多种金属曝露。 以及流行病学背景下的胎盘基因组数据。我们将利用现有资源进行这项研究 在RICHS，一个正在进行的、以前得到资助的队列，使我们能够确定新的环境敏感 以具有成本效益的方式使用生物标志物。通过拟议研究获得的知识和开发的工具 可应用于其他环境，并有可能更广泛地告知宫内感染的影响 在整个生命周期内，环境对健康的影响。 为了进行拟议的研究，我将接受高等生物统计学、系统生物学和分子生物学方面的培训。 方法随着我的研究目标的进展，我的顾问团队在整个过程中不断提供反馈 我们定期安排的会议。通过正规的课程和贾博士提供的指导 陈冠希、克里斯·根宁斯、卡门·马西特、柯昊和钱路，我会得到知识和训练的 有必要发展成为独立的、跨学科的研究人员，专注于阐明 宫内环境暴露与不良生育结局的分子机制。

PROJECT SUMMARY Perturbations during the intrauterine period, including exposures to toxic levels of trace metals, may disrupt appropriate fetal growth and development and adversely impact health throughout the lifespan of the individual. The placenta is the principal organ interpreting cues from the intrauterine environment to inform fetal development, yet, changes in placental transcriptomic activity has not been systematically evaluated as a possible mediator of fetal growth abnormalities. Comprehensively assessing the interrelationship between metal mixture exposure, placental gene activity and fetal growth is becoming feasible with the increasing availability of high-dimensional exposure and genomic data, however, the potential to fully harness the biologic information retained in these large scale data-sets has yet to be realized. To address these existing gaps, we outlined research and training aims to conduct environmental mixture modeling in a population-based study in the context of high-throughput genomics data with verification in a biological system. The proposed study represents the first comprehensive integration of multi-metal exposure and placental genomics data in an epidemiologic setting. We will conduct this study using available resources in RICHS, an ongoing, previously funded cohort, enabling us to identify novel environmentally sensitive biomarkers in a cost-effective manner. The knowledge gained and tools developed through the proposed study may be applied in other settings and have the potential to inform more broadly on the influence of the in utero environment on health throughout the lifespan. To conduct the proposed study, I will train in advanced biostatistics, systems biology and molecular biology methods as I progress through the research aims with continual feedback from my advisory team throughout our regularly scheduled meetings. Through formal coursework and the mentored guidance provided by Drs. Jia Chen, Chris Gennings, Carmen Marsit, Ke Hao and Qian Lu, I will obtain the knowledge and training necessary to develop into an independent, interdisciplinary researcher with a focus on elucidating the molecular mechanism linking in utero environmental exposures to adverse birth outcomes.