MicroRNA Networks in self-sustaining type 2 airway niches in asthma

哮喘自我维持 2 型气道生态位中的 MicroRNA 网络

基本信息

项目摘要

Project Summary Th2 high asthma is defined by persistent airway inflammation that is driven by cytokine crosstalk between epithelial cells and tissue resident innate and adaptive immune cells. The central theme of our collaborative research program is that the focal nature of type 2 inflammation that occurs in asthma reflects the development of persistent type 2 airway niches containing reprogrammed epithelial and immune cells. Disrupting these niches may durably impact asthma pathogenesis. Under normal conditions, transient type 2 responses operate to maintain epithelial barrier function. In asthma, regulatory mechanisms that dampen these responses fail, and type 2 inflammation with epithelial cell reprogramming and mucin hypersecretion persists at focal sites in the airways. The central objective of this project is to define molecular determinants of cell reprogramming that sustain persistent immunopathology in Th2-high asthma. The proposed studies focus on two cell types whose programming directly affects this pathological process: T regulatory (Treg) cells and airway epithelial cells. Our approach builds upon preliminary data indicating that type 2 inflammation and lung dysfunction correlate inversely with the frequency of a subset of airway Tregs, and the positive identification of distinct miRNA families that control the programming of Tregs and epithelial cells. The project is organized into three aims: In Aim 1, we will use single cell sequencing, mRNA and miRNA profiling and mass cytometry to define airway Treg populations, and to compare Treg subsets in persistent airway type 2 niches marked by focal sites of mucus impaction with those that populate unaffected airways. In Aim 2, we will dissect Treg programming using miRNA-directed pathway discovery, a novel experimental framework for probing miRNA:target gene networks. A similar approach will be applied in human airway epithelial cells in Aim 3 to reveal miRNA:target networks that control the cell reprogramming and mucin hypersecretion that marks airway type 2 niches in asthma. If successful, the proposed research will uncover novel genes and pathways critical to the pathology of asthma, advance our understanding how immune regulation mechanisms fail in type 2 airway niches, and suggest strategies to disrupt the inflammation that sustain this disease.
项目摘要 Th 2高哮喘被定义为持续的气道炎症,其由细胞因子之间的串扰驱动。 上皮细胞和组织驻留的先天性和适应性免疫细胞。我们合作的中心主题 一项研究计划认为,哮喘中发生的2型炎症的局部性质反映了哮喘的发展, 持续性2型气道小生境含有重编程上皮细胞和免疫细胞。破坏这些生态位 可能持久影响哮喘发病机制。在正常情况下,瞬态2型响应的操作是 维持上皮屏障功能。在哮喘中,抑制这些反应的调节机制失效, 伴有上皮细胞重编程和粘蛋白高分泌的2型炎症持续存在于 航空公司.该项目的中心目标是确定细胞重编程的分子决定因素, Th 2-高哮喘持续免疫病理学。 拟议的研究集中在两种细胞类型,其编程直接影响这一病理过程: 调节性T(Treg)细胞和气道上皮细胞。我们的方法建立在初步数据的基础上, 2型炎症和肺功能不全与气道THBG亚群的频率呈负相关, 对控制TcB和上皮细胞编程的不同miRNA家族的阳性鉴定。 该项目分为三个目标:在目标1中,我们将使用单细胞测序,mRNA和miRNA分析 和质量细胞计数来定义气道Treg群体,并比较持续性气道2型中的Treg亚群, 以粘液嵌塞的病灶部位为标志的小生境与那些填充未受影响的气道的小生境。在目标2中,我们将 使用miRNA指导的途径发现来剖析Treg编程,这是一种新的实验框架, miRNA:靶基因网络。类似的方法将在Aim 3中应用于人气道上皮细胞, 揭示miRNA:控制细胞重编程和标记气道的粘蛋白高分泌的靶向网络 2型哮喘的小生境。如果成功的话,这项研究将发现新的基因和途径, 哮喘病理学,推进了我们对免疫调节机制如何在2型气道中失效的理解 壁龛,并提出策略,以破坏炎症,维持这种疾病。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Karl Mark Ansel其他文献

Karl Mark Ansel的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Karl Mark Ansel', 18)}}的其他基金

Predoctrol Training in Biomedical Sciences
生物医学科学博士前培训
  • 批准号:
    10192762
  • 财政年份:
    2020
  • 资助金额:
    $ 54.26万
  • 项目类别:
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.
修复伤害和促进实验室安全和包容性实践的恢复性实践。
  • 批准号:
    10393434
  • 财政年份:
    2020
  • 资助金额:
    $ 54.26万
  • 项目类别:
MicroRNA Networks in self-sustaining type 2 airway niches in asthma
哮喘自我维持 2 型气道生态位中的 MicroRNA 网络
  • 批准号:
    10226877
  • 财政年份:
    2012
  • 资助金额:
    $ 54.26万
  • 项目类别:
MicroRNA Networks in self-sustaining type 2 airway niches in asthma
哮喘自我维持 2 型气道生态位中的 MicroRNA 网络
  • 批准号:
    10681275
  • 财政年份:
    2012
  • 资助金额:
    $ 54.26万
  • 项目类别:
MicroRNA Networks in self-sustaining type 2 airway niches in asthma
哮喘自我维持 2 型气道生态位中的 MicroRNA 网络
  • 批准号:
    10472538
  • 财政年份:
    2012
  • 资助金额:
    $ 54.26万
  • 项目类别:
Role of miRNAs in Th2-Driven inflammation in Asthma
miRNA 在 Th2 驱动的哮喘炎症中的作用
  • 批准号:
    8309235
  • 财政年份:
    2011
  • 资助金额:
    $ 54.26万
  • 项目类别:
MicroRNA directed pathway discovery in allergy and asthma
MicroRNA 指导过敏和哮喘通路的发现
  • 批准号:
    10840232
  • 财政年份:
    2011
  • 资助金额:
    $ 54.26万
  • 项目类别:
Cas9 RNP targeting cis-regulatory elements in lymphocytes
Cas9 RNP 靶向淋巴细胞中的顺式调控元件
  • 批准号:
    10630567
  • 财政年份:
    2011
  • 资助金额:
    $ 54.26万
  • 项目类别:
MicroRNA directed pathway discovery in allergy and asthma
MicroRNA 指导过敏和哮喘通路的发现
  • 批准号:
    10433928
  • 财政年份:
    2011
  • 资助金额:
    $ 54.26万
  • 项目类别:
Role of miRNAs in Th2-Driven inflammation in Asthma
miRNA 在 Th2 驱动的哮喘炎症中的作用
  • 批准号:
    8870413
  • 财政年份:
    2011
  • 资助金额:
    $ 54.26万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 54.26万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了