Developmental Core

总结发展核心 将环境措施纳入现有研究的一个主要挑战是捕捉动态 环境的性质，特别是如何回溯而又客观地捕捉它。这是特别的 对HHEAR很重要，因为它可能包括许多横断面的病例对照基因研究 如果使用血液或尿液进行暴露评估。缺乏客观的回溯性生物标志物 提供了有关胎儿和儿童早期接触的程度和时间的信息 外部环境暴露和内部生物过程是环境保护的主要障碍 流行病学。开发核心的主要任务是开发、验证和标准化 精确、不偏不倚地衡量“曝光体”的关键组成部分。我们的方法现在是 能够在一次扫描中测量100,000个特征。然而，请记住，需要 重建过去的暴露，我们将进一步将这项工作扩展到特定生命的追溯生物标记物 包括产前生活在内的各个阶段，有效地提供了相当于前瞻性纵向设计的数据。一个 主要焦点将是客观测量产前的回溯性暴露重建生物标记物 和婴儿环境，众所周知，这对儿童和成人疾病都很重要。我们的 Development Core在过去三年中在 切尔计划。我们开发了基于牙齿基质的生物标记物，利用牙本质生长环来 重建有毒/营养元素和非目标有机化学品暴露的时间和剂量 胎儿的生命和婴儿期。我们还在开发生物标志物，以改进评估的标准方法 新生儿干血点，头发和胎盘，所有这些都可能重建过去暴露在 生命的不同阶段。现在人们认识到，组织结构可以提供暴露和生物 通过化学空间分布提供的毒性信息。我们的核心将应用2D组织生物成像 量化金属和生物分子在组织切片中的空间分布，使用高密度的 分辨率激光质谱仪与多重金属标记免疫标记相结合。我们 正在将其应用于癌症研究，方法是绘制实体肿瘤地图，以包括 暴露在环境中的癌症。这是核心目标要做出贡献的一个突出例子 精密环境医学。发展核心将与非目标资源整合， 这样我们的工作就可以被整合为向HHEAR客户提供的服务。这将会实现的 通过共享人员、资源和每月举行的执行指导委员会会议。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HHEAR网络。Dr。 曼尼什·阿罗拉是核心领导者和资源总监，他还在CHEAR中心发挥了作用。

SUMMARY DEVELOPMENTAL CORE A major challenge to including environmental measures to existing studies is capturing the dynamic nature of the environment, particularly how to capture it retrospectively, yet objectively. This is particularly important for HHEAR since it may include many case control genetic studies that would be cross-sectional if blood or urine were used for exposure assessment. The absence of objective retrospective biomarkers that provide information on both the magnitude and timing of fetal and early childhood exposure to external environmental exposures and internal biological processes is a major barrier in environmental epidemiology. A primary mission of the Developmental Core is to develop, validate and standardize precise, unbiased, approaches of measuring key components of the `exposome'. Our methods are now capable of measuring 100,000 features in a single scan. However, keeping in mind the need for reconstructing past exposure, we will further extend this work to retrospective biomarkers of 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, which are known to be important for both childhood and adult disease. Our Developmental Core has an established track record of innovation over the past three years in the CHEAR Program. We developed tooth matrix-based biomarkers that leverage dentine growth rings to reconstruct the timing and dose of toxic/nutrient elements and untargeted organic chemical exposures in fetal life and infancy. We are also developing biomarkers that improve on the standard methods to assess neonatal dry blood spots, hair and the placenta, all of which can potentially reconstruct past exposure at different stages of life. It is now recognized that tissue architecture can provide exposure and biological information on toxicity via chemical spatial distribution. Our Core will apply 2D 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 are applying this to cancer studies by mapping solid tumors to include spatial information on environmental exposures in cancer. This is one prominent example of the Core aims to contribute to Precision Environmental Medicine. The Developmental Core will integrate with the Untargeted Resource, so that our work can be incorporated as services offered to HHEAR Clients. This will be accomplished through shared personnel, resources and the monthly Executive Steering Committee meetings. Our goal is to bring new biomarkers into the HHEAR network as fully developed, high-throughput platforms. Dr. Manish Arora is the Core Leader, and Director of the Resource, roles he also played in the CHEAR Hub.