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Targeting the alpha v integrin mechanotransduction axis in IPF

Targeting the alpha v integrin mechanotransduction axis in IPF
靶向 IPF 中的 α v 整合素机械转导轴
批准号:
9033145
负责人:
Thomas Harrison Barker
金额:
$7.0万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-04-01 至 2016-07-31

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中文摘要
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英文摘要
 DESCRIPTION (provided by applicant): Idiopathic Pulmonary Fibrosis, or IPF, is a terminal disease affecting as many as 500,000 Americans with no FDA-approved therapies capable of stopping disease progression. The disease is characterized by excessive assembly of extracellular matrix (ECM) by activated fibroblasts termed `myofibroblasts'. Recently, studies have demonstrated that tissue mechanics, specifically tissue stiffness resulting from myofibroblasts assembly of ECM and contraction, is capable of driving the differentiation of myofibroblasts and thus disease progression. In short, myofibroblasts are capable of recruiting more myofibroblasts leading to a disease that progresses unchecked. Despite these recent findings we still do not understand how the process is initiated, nor do we have any therapies that effective halt disease progression. In the current research proposal we hypothesize that an emergent fibroblast subpopulation displays dysregulated mechanotransductive phenotypes due to an inability of these cells to "sense" the stiffness of their environment. These fibroblasts are thus capable of assembling and contracting the ECM, like myofibroblasts, even in soft environments, thus skewing the matrix from normal to pro-fibrotic. We propose to define the aberrant phenotypes, identify the molecular mechanism, and propose a novel approach toward the normalization of aberrant fibroblast mechanotransduction. We will use a host of cell sources from human to mouse, model ECMs from purely synthetic to human disease-derived, and animal models of disease along with advanced biophysical and cell biological assays to complete the project. The research proposed in this application is significant not only in terms of its potential impact on the clinical diagnosis and treatment of IPF, but also in its impact on our understanding of the mechanistic underpinnings of the transition from normal wound healing to fibrotic progression within the lung.
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2022 American Society for Matrix Biology Workshop on Fibroblasts: The Many Faces of Fibroblasts
  • 批准号:
    10540466
  • 项目类别:
  • 资助金额:
    $1.0万
  • 财政年份:
    2022
  • 负责人:
    Thomas Harrison Barker
  • 依托单位:
Modeling to Design Treatments for Idiopathic Lung Fibrosis
  • 批准号:
    10435582
  • 项目类别:
  • 资助金额:
    $54.82万
  • 财政年份:
    2021
  • 负责人:
    Thomas Harrison Barker
  • 依托单位:
Modeling to Design Treatments for Idiopathic Lung Fibrosis
  • 批准号:
    10305193
  • 项目类别:
  • 资助金额:
    $54.82万
  • 财政年份:
    2021
  • 负责人:
    Thomas Harrison Barker
  • 依托单位:
Modeling to Design Treatments for Idiopathic Lung Fibrosis
  • 批准号:
    10646439
  • 项目类别:
  • 资助金额:
    $54.82万
  • 财政年份:
    2021
  • 负责人:
    Thomas Harrison Barker
  • 依托单位:
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