Mount Sinai CHEAR Laboratory Network Hub Developmental Core

项目摘要开发核心 儿童环境健康研究面临的一个主要挑战是捕捉环境的动态性质， 特别是如何追溯性地捕捉它。缺乏先进的曝光工具来解决曝光时间问题 限制对易感性的关键窗口的研究--当个体高度易受感染时的生命阶段 暴露在环境中。未来的出生队列可能会捕捉到这些关系，但在 时间和金钱。缺乏客观的回溯性生物标志物来提供这两个方面的信息 胎儿和儿童早期接触多种化学物质的大小和时间是 环境流行病学。开发核心的主要任务是开发、验证和 标准化特定生命阶段多种化学物质暴露的准确、无偏见、可追溯的生物标志物 包括产前寿命，有效地提供了相当于前瞻性纵向设计的数据。一个主要的焦点 将是可追溯的暴露重建生物标记物，客观地测量产前和婴儿 即使样本是在童年或青春期采集的，也不会影响环境。这些将包括牙齿 利用牙本质生长环重建有毒/营养物质的时间和剂量的基于基质的生物标记物 胎儿期和婴儿期的元素和有机化学暴露。我们还将开发基于牙科基质的 非靶向分析，以创建“回溯性动态暴露组”生物标记物。同时，我们还将发展 使用创新的毛发分析方法评估胚胎和早期胎儿暴露的方法 孕妇重建临时性妊娠周化学暴露的研究。现在人们认识到，组织 在进行暴露评估的任何化学分析时，必须考虑体系结构。我们的核心将适用于 多维(2D和3D)组织生物成像，量化金属和 组织切片中生物分子的高分辨率激光基质谱联用 多重金属标记免疫标记。我们还将开发金属蛋白质组学技术，可以 研究金属毒素代谢及其对正常金属动态平衡的影响。最后，核心联合领导者 (Baccarelli)是著名的环境表观遗传学专家，将开发新的生物反应 解决DNA甲基化和组蛋白引起的DNA构象状态的生物标记物 修改。他还将与Core Leader(Arora)合作测量miRNA和mtDNA生物标记物 可以概括过去对环境的生物反应的头发，从而补充了阿罗拉博士的 研究激光消融、电感耦合等离子体质谱和毛发金属。发展核心将与其他核心融为一体 资源，这样我们的工作就可以合并为三个中心资源提供的服务。这将是 通过共享人员、资源和每月召开的执行指导委员会会议来完成。 我们的目标是将新的生物标记物作为完全开发的高通量平台引入CHEAR网络。

Project Summary Developmental Core A major challenge to children's environmental health research is capturing the dynamic nature of environment, particularly how to capture it retrospectively. The lack of advanced exposure tools to address exposure timing limits research on critical windows of susceptibility – life stages when individuals are highly vulnerable to environmental exposures. Prospective birth cohorts may capture these relationships, but are expensive both in time and money. The absence of objective retrospective biomarkers that provide information on both the magnitude and timing of fetal and early childhood exposure to multiple chemicals is a major barrier in environmental epidemiology. The primary mission of the Developmental Core is to develop, validate and standardize precise, unbiased, retrospective biomarkers of multi-chemical exposures at specific life stages including prenatal life, effectively providing data equivalent to a prospective longitudinal design. A major focus will be retrospective exposure reconstruction biomarkers that objectively measure prenatal and infant environment, even when samples are collected during childhood or adolescence. These will include tooth matrix-based biomarkers that exploit dentine growth rings to reconstruct the timing and dose of toxic/nutrient elements and organic chemical exposures in fetal life and infancy. We will also develop dental matrix based untargeted assays to create a `retrospective dynamic exposome' biomarker. In parallel, we will also develop methods to estimate embryonic and early fetal exposure using innovative assays of hair collected from pregnant women to reconstruct temporal periconceptual chemical exposures. It is now recognized that tissue architecture must be considered during any chemical analyses for exposure assessment. Our Core will apply multidimensional (2D and 3D) tissue bio-imaging that quantifies the spatial distribution of both metals and biomolecules within tissue sections using high-resolution laser-based mass spectrometry combined with multiplexed metal-tagged immunolabelling. We will also develop metalloproteomic techniques that can investigate metal-toxin metabolism and its effects on normal metal homeostasis. Finally, the Core Co-Leader (Baccarelli) is a renowned expert in environmental epigenetics and will develop novel biological response biomarkers that address the DNA conformational states that arise from DNA methylation and histone modifications. He will also work jointly with Core Leader (Arora) on measuring miRNA and mtDNA biomarkers in hair that can recapitulate past biological response to the environment, thereby complementing Dr. Arora's work on laser ablation ICP-MS and hair metals. The Developmental Core will integrate with the other Resources, so that our work can be incorporated as services offered by the three Hub Resources. This will be accomplished through shared personnel, resources and the monthly Executive Steering Committee meetings. Our goal is to bring new biomarkers into the CHEAR network as fully developed, high-throughput platforms.