Scientific Human Biomarker Exposure Monitoring Core (HEMC) for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study

空气污染科学人体生物标志物暴露监测核心 (HEMC) 扰乱心肺总体健康 (AIRHEALTH) 研究中的炎症小体调节

• 批准号: 10269332
• 负责人: Francois Haddad
• 金额: $ 22.58万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10269332
• 关键词: ATAC-seq; Air Pollution; Biological Assay; Biological Markers; CXCL9 gene; Cardiopulmonary; Cardiovascular system; Cell Culture Techniques; Cells; Chromatin; Clinical; Collaborations; Custom; DNA; Data; Endothelium; Environmental Exposure; Epigenetic Process; Exposure to; Fibrin fragment D; Fibrinogen; Gene Activation; Gene Expression Profiling; Gene Proteins; Genes; Goals; Health; Heart; Hemostatic function; Human; Immune; Immunoassay; Immunologic Monitoring; Individual; Inflammasome; Infrastructure; Injury; Institution; Interleukin-1 beta; Interleukin-18; Interleukin-6; Laboratories; Leptin; Location; Lung; Metabolic stress; Modification; Molecular; Molecular Analysis; Monitor; Nitrogen Dioxide; Oxidative Stress; Ozone; Pathway interactions; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Pollution; Precision Medicine Initiative; Prevention; Procedures; Process; Program Research Project Grants; Proteomics; Quality Control; RNA; Recording of previous events; Regulation; Research Personnel; Retrieval; Risk; Sampling; Sampling Studies; Services; Site; Specimen; Standardization; Study models; TNF gene; Technology; Testing; Time; Transcript; Transforming Growth Factor beta; Vascular Cell Adhesion Molecule-1; Work; aryl hydrocarbons; base; biobank; circulating biomarkers; coarse particles; cohort; experience; experimental study; fine particles; histone methylation; immune activation; innovation; intercellular cell adhesion molecule; medical schools; monocyte; pollutant; quality assurance; residence; synergism; therapeutic target; tool; web portal

ABSTRACT: HUMAN BIOMARKER EXPOSURE MONITORING CORE (HEMC) The Scientific Human Biomarker Exposure Monitoring Core (HEMC) is a state-of-the-art Core Laboratory at Stanford School of Medicine that builds on the extensive experience of the Stanford Human Immune Monitoring Core Laboratory (HIMC). The HEMC will serve the aims of Projects 1, 2 and 3 by performing comprehensive, standardized immune-based cell culture assays, and cardiovascular assays. The overarching goals of the HEMC are to manage and process biomarker samples, define the multidimension biomarker profile of pollutant exposure, and to provide state of the art assays for epigenic modifications relevant to pollutant exposure. The results of the experiments performed by the HEMC will be central to the individual projects of this PPG by providing needed samples to the individual projects and guiding the use of the most informative samples for mechanistic and modeling studies. To this end, our three specific aims are: Aim 1. To centrally bank air pollution cohort plasma, peripheral blood mononuclear cells (PBMCs), RNA, and DNA, and to provide those specimens to the PPG Projects for both standardized and customized assays; Aim 2. To provide standardized targeted proteomics and gene expression assays instrumental for characterizing pollution exposure signature (PES) that will be complimentary to the specific projects of the PPG; and Aim 3. To provide a standardized, innovative epigenetic assay to enhance mechanistic findings in all projects. The HEMC brings together an unparalleled set of Stanford technologies for inflammasome monitoring and mechanistic work. We have given careful and systematic thought to the selection of assays to be performed that will evaluate different aspects of pollutant exposure. Many of technologies used in the HEMC have been largely developed and optimized at Stanford and validated by institutions outside Stanford, increasing our confidence for their application to the PPG projects. In collaboration with the DMAC, the HEMC will offer innovative tools and support for this proposed PPG to enable analysis of molecular mechanisms and to find therapeutic targets for the prevention and treatment of pollution- related cardiopulmonary risks, as proposed in Projects 1, 2, and 3.

摘要：人体生物标志物暴露监测核心（HEMC） 科学人类生物标志物暴露监测核心（HEMC）是一个最先进的核心实验室， 斯坦福大学医学院，建立在斯坦福大学人类免疫监测的丰富经验 核心实验室（HIMC）。HEMC将为项目1、2和3的目标服务， 标准化的基于免疫的细胞培养测定和心血管测定。HEMC的总体目标 生物标志物样品的管理和处理，确定污染物的多维生物标志物谱 暴露，并提供与污染物暴露相关的表观修饰的最新测定。的 由HEMC进行的实验结果将是本PPG各个项目的核心， 为各个项目提供所需的样本，并指导使用信息量最大的样本， 机制和模型研究。为此，我们的三个具体目标是：目标1。将空气污染集中起来 队列血浆、外周血单核细胞（PBMC）、RNA和DNA，并提供这些标本 PPG项目的标准化和定制化检测;目标2.提供标准化的针对性 蛋白质组学和基因表达分析，用于表征污染暴露特征（PES）， 将对项目规划小组的具体项目起到补充作用;目标3。提供标准化、创新化的 表观遗传分析，以加强所有项目的机制发现。HEMC汇集了无与伦比的 斯坦福大学的炎性小体监测和机械工作的技术。我们已经仔细地， 系统地考虑要进行的分析的选择，以评估污染物的不同方面 exposure. HEMC中使用的许多技术在很大程度上是在斯坦福大学开发和优化的， 经过斯坦福大学以外的机构验证，增加了我们对PPG项目应用的信心。在 HEMC将与DMAC合作，为拟议的PPG提供创新工具和支持， 分析分子机制，寻找防治污染的治疗靶点- 相关心肺风险，如项目1、2和3中所述。