Mount Sinai CHEAR Laboratory Network Hub Developmental Core
西奈山 CEAR 实验室网络中心发展核心
基本信息
- 批准号:9062194
- 负责人:
- 金额:$ 104万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-30 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAdolescenceArchitectureBackBiochemicalBiologicalBiological AssayBiological MarkersBirthBloodCase-Control StudiesChemical ExposureChemicalsChildChild DevelopmentChild health careChildhoodCohort StudiesComplementConceptionsCoupledDNADNA MethylationDataDentalDentinDevelopmentDevelopmental ProcessDisciplineDoseElderlyElementsEmbryoEnrollmentEnvironmentEnvironmental EpidemiologyEnvironmental ExposureEnvironmental HealthEpigenetic ProcessEventExposure toGenesGeneticGenetic ResearchGenomicsGenotypeGoalsGrantGrowthHairHealthHomeostasisHuman ResourcesIndividualInductively Coupled Plasma Mass SpectrometryInfantLaboratoriesLasersLifeLinkMass Spectrum AnalysisMeasuresMetabolismMetalsMethodsMicroRNAsMindMissionMitochondrial DNAMolecular ConformationNatureNutrientOnset of illnessOrganic ChemicalsPerinatal ExposurePhenotypePlacentaPlayPredispositionPregnant WomenResearchResearch DesignResearch PersonnelResolutionResourcesRoleSamplingScienceServicesSpatial DistributionSpecimenStagingStressTechniquesTechnologyTimeTissuesTooth structureUrineWomanWorkbasebioimagingcase controlcohortdeciduous toothearly childhoodfetalhistone modificationhuman DNA sequencinginfancyinnovationinsightinterestlongitudinal designmeetingsnovelprenatalprogramsprospectivereconstructionresponsetooltoxin metabolism
项目摘要
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.
项目概要开发核心
儿童环境健康研究的一个主要挑战是捕捉环境的动态性质,
特别是如何回顾性地捕捉它。缺乏先进的曝光工具来解决曝光时间问题
限制了对易感性关键窗口的研究-个人在生命阶段极易受到
环境暴露。前瞻性出生队列可能会捕捉到这些关系,但无论是在
时间和金钱。缺乏客观的回顾性生物标志物,可以提供关于
胎儿和幼儿暴露于多种化学品的程度和时间是一个主要障碍,
环境流行病学开发核心的主要使命是开发、验证和
特定生命阶段多化学品暴露标准化精确、无偏倚、回顾性生物标志物
包括产前生活,有效地提供了相当于前瞻性纵向设计的数据。一个主要重点
将是回顾性暴露重建生物标志物,客观地测量产前和婴儿
即使是在儿童或青少年时期收集的样本,也会受到环境的影响。其中包括牙齿
基于基质的生物标志物,利用牙本质生长环重建毒性/营养素的时间和剂量
元素和有机化学品暴露在胎儿和婴儿期。我们还将开发基于牙科基质的
非靶向测定,以创建“回顾性动态暴露组”生物标志物。与此同时,我们还将开发
使用从以下组织收集的毛发的创新分析来估计胚胎和早期胎儿暴露的方法:
孕妇重建时间的近概念化学品暴露。现在人们认识到,
在进行接触评估的任何化学分析过程中,必须考虑到结构。我们的核心将适用于
多维(2D和3D)组织生物成像,其量化金属和
使用高分辨率基于激光的质谱法结合
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,
研究金属毒素代谢及其对正常金属稳态的影响。最后,核心领导人
(Baccarelli)是环境表观遗传学方面的著名专家,将开发新颖的生物反应
解决DNA甲基化和组蛋白引起的DNA构象状态的生物标志物
修改.他还将与核心领导人(Arora)共同研究测量miRNA和mtDNA生物标志物
在头发中,可以重现过去对环境的生物反应,从而补充阿罗拉博士的
研究激光烧蚀ICP-MS和头发金属。发展核心将与另一个
资源,这样我们的工作就可以被合并为三个中心资源提供的服务。这将是
通过共享人员、资源和每月举行执行指导委员会会议,实现了这一目标。
我们的目标是将新的生物标志物作为充分开发的高通量平台引入CHEMICAL网络。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Manish Arora其他文献
Manish Arora的其他文献
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{{ truncateString('Manish Arora', 18)}}的其他基金
Early Warning Systems for Childhood and Adult Disorders
儿童和成人疾病早期预警系统
- 批准号:
10382421 - 财政年份:2020
- 资助金额:
$ 104万 - 项目类别:
Early Warning Systems for Childhood and Adult Disorders
儿童和成人疾病早期预警系统
- 批准号:
10624212 - 财政年份:2020
- 资助金额:
$ 104万 - 项目类别:
Early Warning Systems for Childhood and Adult Disorders
儿童和成人疾病早期预警系统
- 批准号:
10171850 - 财政年份:2020
- 资助金额:
$ 104万 - 项目类别:
Early Warning Systems for Childhood and Adult Disorders
儿童和成人疾病早期预警系统
- 批准号:
9729176 - 财政年份:2020
- 资助金额:
$ 104万 - 项目类别:
Mount Sinai HHEAR Network Untargeted Lab Hub
西奈山 HHEAR 网络非目标实验室中心
- 批准号:
10176494 - 财政年份:2019
- 资助金额:
$ 104万 - 项目类别:
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