Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies

气道上皮细胞基因调控:新机制和治疗策略

基本信息

  • 批准号:
    10579268
  • 负责人:
  • 金额:
    $ 96.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-04-15 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The epithelium that lines the airway comprises a variety of specialized cell types that play essential roles in lung health. Changes in the epithelium are prominent features of asthma and other common lung diseases. During normal differentiation, dramatic changes in gene expression are required for the development of the unique functional capabilities of the basal, secretory, and ciliated cell populations within the epithelium. Furthermore, in airway disease, each cell type has distinctive gene expression changes in response to pathogenic cytokines. Over the past two decades, we have used transgenic mouse modeling, human cell culture, and clinical studies to identify molecular mechanisms that underlie changes in epithelial gene expression that contribute to airway obstruction in asthma. Although we and others have gained tremendous insights from mouse models, our overall goal of understanding the biology underlying asthma and other human airway diseases has increasingly led us to focus on developing appropriate human experimental systems. In the past several years, we and our collaborators have developed a set of powerful approaches including single cell RNA-seq, ChIP-seq, massively parallel reporter assays, and CRISPR-mediated gene editing, to address mechanistic questions in primary human airway epithelial cells. These approaches now enable us to perform potentially groundbreaking experiments that give new insights into airway epithelial cell complexity, identify key regulators of gene expression and epithelial cell function, and reveal how specific airway epithelial gene regulators contribute to asthma and other airway diseases. Most disease-associated genetic variants are found in regulatory regions, and our work has important implications for understanding genetic contributions to airway disease risk. We will also work to apply insights about gene regulation to develop approaches for therapeutic reprogramming of the epithelium to prevent, cure, or treat disease. The environment at UCSF provides access to creative collaborators, cutting-edge technologies, and key clinical resources and affords outstanding opportunities for working with early career investigators who will be well positioned to continue to move the field forward.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
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David J Erle其他文献

Differential gene expression by integrin β7+ and β7- memory T helper cells
  • DOI:
    10.1186/1471-2172-5-13
  • 发表时间:
    2004-07-05
  • 期刊:
  • 影响因子:
    2.700
  • 作者:
    Madeleine W Rodriguez;Agnés C Paquet;Yee Hwa Yang;David J Erle
  • 通讯作者:
    David J Erle

David J Erle的其他文献

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{{ truncateString('David J Erle', 18)}}的其他基金

Asthma Endotypes: Mechanisms and Consequences for Airway Epithelium and Mucus
哮喘内型:气道上皮和粘液的机制和后果
  • 批准号:
    10371127
  • 财政年份:
    2020
  • 资助金额:
    $ 96.9万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10371122
  • 财政年份:
    2020
  • 资助金额:
    $ 96.9万
  • 项目类别:
Understanding Asthma Endotypes
了解哮喘内型
  • 批准号:
    10165891
  • 财政年份:
    2020
  • 资助金额:
    $ 96.9万
  • 项目类别:
Understanding Asthma Endotypes
了解哮喘内型
  • 批准号:
    10165887
  • 财政年份:
    2020
  • 资助金额:
    $ 96.9万
  • 项目类别:
Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies
气道上皮细胞基因调控:新机制和治疗策略
  • 批准号:
    10586412
  • 财政年份:
    2019
  • 资助金额:
    $ 96.9万
  • 项目类别:
Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies
气道上皮细胞基因调控:新机制和治疗策略
  • 批准号:
    9915971
  • 财政年份:
    2019
  • 资助金额:
    $ 96.9万
  • 项目类别:
Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies
气道上皮细胞基因调控:新机制和治疗策略
  • 批准号:
    10349455
  • 财政年份:
    2019
  • 资助金额:
    $ 96.9万
  • 项目类别:
Defining A Comprehensive Reference Profile of Circulating Human Extracellular RNA
定义循环人类细胞外 RNA 的综合参考谱
  • 批准号:
    8775079
  • 财政年份:
    2014
  • 资助金额:
    $ 96.9万
  • 项目类别:
Massively parallel identification of functional 3' UTR variants in asthma
哮喘功能性 3 UTR 变异的大规模并行鉴定
  • 批准号:
    8901295
  • 财政年份:
    2014
  • 资助金额:
    $ 96.9万
  • 项目类别:
Defining A Comprehensive Reference Profile of Circulating Human Extracellular RNA
定义循环人类细胞外 RNA 的综合参考谱
  • 批准号:
    9449991
  • 财政年份:
    2014
  • 资助金额:
    $ 96.9万
  • 项目类别:

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气道疾病暴露组分析以解开哮喘疾病的决定因素 (EXPAND-Asthma) 中心
  • 批准号:
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  • 财政年份:
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  • 批准号:
    10723956
  • 财政年份:
    2023
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定义气道疾病、COPD 恶化和治疗反应的基因表达特征
  • 批准号:
    10733573
  • 财政年份:
    2023
  • 资助金额:
    $ 96.9万
  • 项目类别:
Hydrogen Sulfide in Neonatal Airway Disease
新生儿气道疾病中的硫化氢
  • 批准号:
    10603293
  • 财政年份:
    2023
  • 资助金额:
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Impact of Maternal Arsenic Exposure on Offspring's Epigenetic Reprogramming of Allergic Airway Disease
母亲砷暴露对后代过敏性气道疾病表观遗传重编程的影响
  • 批准号:
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    2023
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    $ 96.9万
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厌氧微生物群在囊性纤维化气道疾病轨迹中的作用
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  • 财政年份:
    2023
  • 资助金额:
    $ 96.9万
  • 项目类别:
Immune Mediators of IL-22 Signaling Alter Allergic Airway Disease
IL-22 信号的免疫介质改变过敏性气道疾病
  • 批准号:
    10853347
  • 财政年份:
    2023
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假单胞菌脂质 A 结构在 CF 气道疾病进展中的微生物适应
  • 批准号:
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厌氧微生物群在囊性纤维化气道疾病轨迹中的作用
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指导炎症性气道疾病领域以患者为中心的研究人员
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    10657746
  • 财政年份:
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