Developmental Core

发展核心

• 批准号: 10453435
• 负责人: Manish Arora
• 金额: $ 16.56万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-11 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453435
• 关键词: Address; Adult; Amyotrophic Lateral Sclerosis; Architecture; Automated Annotation; Biological; Biological Markers; Biological Process; Biometry; Blood; Brain; Chemical Exposure; Chemicals; Child; Childhood; Client; Computer Analysis; Computer software; Computing Methodologies; Data; Data Set; Development; Disease; Dose; Drug Screening; Elements; Environment; Environmental Epidemiology; Environmental Exposure; Environmental Medicine; Event; Exposure to; Fetal Development; Genetic study; Goals; Growth; Hair; Health; Hormones; Human; Human Resources; Human body; Individual; Infant; Laboratories; Lasers; Libraries; Life; Link; Lipids; Machine Learning; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Metal exposure; Metals; Methods; Mind; Mission; Molecular; Molecular Profiling; Nature; Neonatal; Nutrient; Organic Chemicals; Outcome; Phenotype; Placenta; Plasma; Play; Predisposition; Process; Rare Diseases; Reference Standards; Research Personnel; Resolution; Resources; Role; Sample Size; Scanning; Series; Services; Signal Transduction; Solid Neoplasm; Source; Spatial Distribution; Spottings; Standardization; Surface; Systems Biology; Technology; Time; Tissue imaging; Tissues; Tooth structure; Toxic effect; Tumor Bank; United States National Institutes of Health; Urine; Vendor; Work; autism spectrum disorder; base; bioimaging; case control; computational platform; early childhood; epidemiology study; experience; fetal; graphical user interface; high dimensionality; high standard; improved; infancy; innovation; longitudinal design; machine learning method; meetings; metabolomics; neural network; new technology; novel; novel strategies; prenatal; prenatal exposure; programs; prospective; reconstruction; response; response biomarker; small molecule libraries; statistics; tissue mapping; toxic metal; uptake; user-friendly; wearable sensor technology

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.

摘要材料核心 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，特别是如何回顾性地捕捉它，但客观。这是特别 这对HHEAR很重要，因为它可能包括许多病例对照遗传学研究， 是否使用血液或尿液进行接触评估。缺乏客观的回顾性生物标志物 提供关于胎儿和儿童早期暴露于 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使命是开发、验证和标准化 精确、公正的方法来衡量“麻烦”的关键组成部分。我们的方法现在 能够在一次扫描中测量10万个特征。然而，考虑到需要 重建过去的暴露，我们将进一步扩大这项工作的回顾性生物标志物的特定生活 阶段，包括产前生活，有效地提供数据相当于一个前瞻性的纵向设计。一 主要焦点将是回顾性暴露重建生物标志物， 和婴儿的环境，这是众所周知的是重要的儿童和成人疾病。我们 在过去三年中，发展核心在创新方面有着良好的记录， CHEMICAL计划。我们开发了基于牙齿基质的生物标志物，利用牙本质生长环， 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， 胎儿期和婴儿期我们还在开发生物标志物，改进标准方法， 新生儿干血斑，头发和胎盘，所有这些都有可能重建过去的接触， 生命的不同阶段。现在认识到，组织结构可以提供暴露和生物学特性。 通过化学空间分布提供毒性信息。我们的核心将应用2D组织生物成像， 量化了组织切片内金属和生物分子的空间分布，使用高- 分辨率激光质谱结合多重金属标记免疫标记。我们 正在将其应用于癌症研究，通过绘制实体肿瘤， 癌症的环境暴露。这是一个突出的例子，说明核心的目标是促进 精准环境医学发展核心将与非目标资源整合， 以便我们的工作可以作为提供给HHEAR客户的服务。这将是完成 通过共享人员、资源和每月举行执行指导委员会会议，我们的目标 将新的生物标志物引入HHEAR网络，作为完全开发的高通量平台。博士 Manish Arora是核心领导者，也是资源总监，他也在CHEMICAL Hub担任过角色。