Identifying Multidimensional Omics Profiles Associated with Cardiovascular and Pulmonary Responses to Chronic and Acute Air Pollution Exposure (Project 2) for AIRHEALTH Study

确定与慢性和急性空气污染暴露的心血管和肺部反应相关的多维组学概况(项目 2),用于空气健康研究

基本信息

  • 批准号:
    10269335
  • 负责人:
  • 金额:
    $ 50.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

ABSTRACT: PROJECT 2 Lung and cardiac diseases are complex disorders with underlying chronic inflammation, which can be induced or worsened by exposure to air pollution. Thus, understanding the molecular mechanisms by which air pollution activates the immune system and inflammation is essential to developing therapies. The recently reported association of the pro-inflammatory cytokine, IL-1β, with air pollution-linked pulmonary and cardiovascular inflammation presents the hypothesis that IL-1β could be the common mediator of downstream inflammatory immune responses linked to air pollution. Project 1 directly tests the hypothesis that IL-1β or other pathways are induced by air pollution, and examines the effect of air pollution and IL-1β or other pathways on immune cell and lung cell function using blood samples from three well-characterized cohorts that had been exposed to air pollution. Project 3 tests the hypothesis that IL-1β or other pathways are involved in immune signaling in cardiovascular tissue by directly by studying engineered heart cells' function after exposure to plasma samples from the same three cohorts. In Project 2, we will synergize and harmonize our studies with Projects 1 and 3 by developing hypotheses using specific systems biology approaches to understand the molecular circuitry induced by IL-1β in response to chronic and acute air pollution. There will be no redundancy with Project 1 and 3 or core laboratory experiments because we plan to perform unique-omics level experiments on blood samples from the three cohorts. We hypothesize that IL-1β or other pathways induce a gene/protein/metabolite expression response that plays a role in the pathophysiology of air pollution-linked immune system activation. Our results in Project 2 could provide a comprehensive, global view of IL-1β−related and IL-1β non-related responses in blood, lung, and/or cardiac tissues with fine-scale characterization of time-dependent and cytokine- specific response patterns. To characterize this response, we will perform assays to identify abundances of transcripts, proteins, and metabolites in samples from the three cohorts exposed to air pollution. We plan to identify networks of molecules associated or not associated with IL-1β pathways, which are differentially expressed in chronic versus acute air pollution. Our aims are Aim 1. to determine whether IL1α, IL1β, and IL36γ and other markers are upregulated in individuals exposed to air pollution vs healthy control (e.g. cohort with no air pollution exposure time point) in blood, lung, and cardiac tissues; Aim 2. to determine whether ATPases, glucokinase, HSP70, and MAPkinases and other pathways are upregulated in air pollution exposure in blood sample; and Aim 3. to determine whether the metabolites associated with lipid metabolism and lipogenesis are upregulated in air pollution exposure. We expect that our data will generate hypotheses about pathological mechanisms that can be shared collaboratively with Projects 1 and 3 and the core HEMC to test biomarkers and drug targets for the PPG
摘要:项目2 肺病和心脏病是一种复杂的疾病,有潜在的慢性炎症,可以诱发 或因暴露在空气污染中而恶化。因此,了解空气污染的分子机制 激活免疫系统和炎症是开发治疗方法所必需的。最近报道的 促炎细胞因子IL-1β与空气污染所致肺和心血管疾病的关系 炎症提出的假设是,IL-1β可能是下游炎症的共同介质 与空气污染有关的免疫反应。项目1直接测试了IL-1β或其他途径是 并检测空气污染和IL-1β或其他途径对免疫细胞和 用暴露于空气中的三个特征良好的队列的血液样本研究肺细胞功能 污染。项目3测试了IL-1、β或其他途径参与免疫信号转导的假设 直接通过研究工程心脏细胞暴露于血浆样本后的功能来研究心血管组织 来自相同的三个队列。在项目2中,我们将与项目1和项目3协同和协调我们的研究 通过使用特定的系统生物学方法开发假说来理解分子电路 由IL-1β诱导的对慢性和急性空气污染的反应。项目1不会有冗余,并且 3或核心实验室实验,因为我们计划对血液样本进行独特的组学水平实验 从三个队列中选出。我们假设IL-1β或其他途径诱导一种基因/蛋白质/代谢物 在空气污染相关免疫系统激活的病理生理学中起作用的表达反应。 我们在项目2中的结果可以提供与IL-1β−相关和与IL-1β无关的全面的全球视角 血液、肺和/或心脏组织中的反应,具有时间依赖性和细胞因子的精细特征 特定的响应模式。为了描述这种反应,我们将进行化验以确定其丰度 暴露在空气污染中的三组样本中的转录本、蛋白质和代谢物。我们计划 识别与IL-1β通路相关或不相关的分子网络,这些分子网络是不同的 表现为慢性空气污染与急性空气污染。我们的目标是1.确定IL1α、IL1β和IL36γ 而其他标志物在暴露于空气污染的个体与健康对照组相比上调(例如,没有 空气污染暴露时间点)在血液、肺和心脏组织中;目的2.确定ATPase, 葡萄糖激酶、HSP70和MAPkinase等途径在血液中的空气污染暴露中上调 目的3.确定与脂肪代谢和脂肪生成有关的代谢物是否 暴露在空气污染中的比例上升。我们预计我们的数据将产生关于病理性的假说 可与项目1和3以及核心HEMC协作共享以测试生物标记物的机制 和PPG的药物靶标

项目成果

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MICHAEL P. SNYDER其他文献

MICHAEL P. SNYDER的其他文献

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{{ truncateString('MICHAEL P. SNYDER', 18)}}的其他基金

Precancer Atlas of Familial Adenomatous Polyposis
家族性腺瘤性息肉病癌前图谱
  • 批准号:
    10900834
  • 财政年份:
    2023
  • 资助金额:
    $ 50.86万
  • 项目类别:
Organ Specific Project
器官特定项目
  • 批准号:
    10709580
  • 财政年份:
    2022
  • 资助金额:
    $ 50.86万
  • 项目类别:
Organ Specific Project
器官特定项目
  • 批准号:
    10531083
  • 财政年份:
    2022
  • 资助金额:
    $ 50.86万
  • 项目类别:
PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOME
人类基因组监管区域图谱制作中心
  • 批准号:
    10241080
  • 财政年份:
    2021
  • 资助金额:
    $ 50.86万
  • 项目类别:
The Chromium Connect, an integrated and robotic system to automate library preparation for single-cell RNA-Seq
Chromium Connect,一个集成的机器人系统,用于自动进行单细胞 RNA 测序的文库制备
  • 批准号:
    10171302
  • 财政年份:
    2021
  • 资助金额:
    $ 50.86万
  • 项目类别:
Identifying Multidimensional Omics Profiles Associated with Cardiovascular and Pulmonary Responses to Chronic and Acute Air Pollution Exposure (Project 2) for AIRHEALTH Study
确定与慢性和急性空气污染暴露的心血管和肺部反应相关的多维组学概况(项目 2),用于空气健康研究
  • 批准号:
    10460331
  • 财政年份:
    2021
  • 资助金额:
    $ 50.86万
  • 项目类别:
Multi-Modal Wireless COVID Monitoring & Infection Alerts for Concentrated Populations
多模式无线新冠肺炎监测
  • 批准号:
    10594946
  • 财政年份:
    2020
  • 资助金额:
    $ 50.86万
  • 项目类别:
Multi-Modal Wireless COVID Monitoring & Infection Alerts for Concentrated Populations
多模式无线新冠肺炎监测
  • 批准号:
    10320756
  • 财政年份:
    2020
  • 资助金额:
    $ 50.86万
  • 项目类别:
Multi-Modal Wireless COVID Monitoring & Infection Alerts for Concentrated Populations
多模式无线新冠肺炎监测
  • 批准号:
    10274232
  • 财政年份:
    2020
  • 资助金额:
    $ 50.86万
  • 项目类别:
Genomics Diversity Summer Program (GDSP) at Stanford
斯坦福大学基因组多样性暑期项目 (GDSP)
  • 批准号:
    10408049
  • 财政年份:
    2019
  • 资助金额:
    $ 50.86万
  • 项目类别:

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Impacts of Acute Ambient Air Pollution Exposure on Women's Reproductive Health: Identifying Mechanisms and Susceptible Reproductive Processes Across the Menstrual Cycle and Early Pregnancy
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  • 批准号:
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Identifying Multidimensional Omics Profiles Associated with Cardiovascular and Pulmonary Responses to Chronic and Acute Air Pollution Exposure (Project 2) for AIRHEALTH Study
确定与慢性和急性空气污染暴露的心血管和肺部反应相关的多维组学概况(项目 2),用于空气健康研究
  • 批准号:
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    $ 50.86万
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Identifying Multidimensional Omics Profiles Associated with Cardiovascular and Pulmonary Responses to Chronic and Acute Air Pollution Exposure (Project 2) for AIRHEALTH Study
确定与慢性和急性空气污染暴露的心血管和肺部反应相关的多维组学概况(项目 2),用于空气健康研究
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空气污染、气候和慢性阻塞性肺病:对加拿大人口的急性和长期影响
  • 批准号:
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ASSESSING THE ACUTE AND CHRONIC CARDIO-RESPIRATORY HEALTH IMPACTS OF AMBIENT AIR POLLUTION IN CHINA
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The Acute Effects of Ambient Air Pollution in Susceptible Populations
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Acute and chronic effects of traditional and novel markers of air pollution on blood markers of inflammationand coagulation
传统和新型空气污染标志物对炎症和凝血血液标志物的急性和慢性影响
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The Effect of Acute Air Pollution Exposure on the Incidence of Appendicitis: A Multi-City Study
急性空气污染暴露对阑尾炎发病率的影响:一项多城市研究
  • 批准号:
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  • 财政年份:
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Particulate Air Pollution and Acute Ischemic Stroke
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    6935790
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    2005
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