Pathogenic Exosomes in COPD

COPD 中的致病性外泌体

基本信息

  • 批准号:
    10571796
  • 负责人:
  • 金额:
    $ 102.61万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-01 至 2030-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The thesis of this R35 Program is that immune cell derived “pathogenic exosomes” are key players in chronic obstructive pulmonary disease (COPD) and that their role can be modeled in a smoking mouse model of exosome transfer to attain novel understanding of the disease which can in turn be applied to COPD. This R35 Program is at the cutting edge of innovation having discovered the existence of alpha-1 antitrypsin (α-1AT) resistant neutrophil elastase (NE)+ neutrophil (PMN)-derived exosomes in COPD patients. In doing so, the Program has challenged the concept that protease activity is solely solution phase and shown extracellular matrix (ECM) proteolytic activity is hugely enhanced by protease attachment to the extracellular vesicle (EV) surface. Consequently, we: i) describe what appears to be the first EV that can transfer a COPD-like phenotype from humans to mice; ii) elucidate a new mechanism by which proteases escape anti-protease inactivation, leading to ECM degradation and cell death via receptor-interacting protein kinase 3 (RIPK3); iii) describe a new model that transfers a COPD phenotype from cigarette smoke (CS) exposed mice to naïve mice via immune cell- derived exosomes; iv) use the mouse model to discover a new CS induced protective mechanism against exosomal damage as well as a mechanism for exosomal self-propagation; v) uncover new therapeutic targets for exosomal damage and; vi) translate the new findings to better understand disease in COPD patients and smokers. Another highly significant aspect of this research Program is training/mentoring. In the past ten years, which includes the PI's inaugural R35 grant, the PI has been or is currently mentor to two PhD students, five medical students, an MD/PhD student, six K awardees, four postdoctoral trainees, a pulmonary fellow, and a cardiology fellow. The PI currently mentors seven junior faculty members. Overall, our Program is both multidisciplinary – employing chemistry, biochemistry, molecular and cell biology, animal physiology, etc. – and translational in pairing basic scientists with physician scientists. Our team and trainees fulfill the NHLBI/NIH mission to have diversity by including African American, Latina, Asian, and Caucasian members. Our program fulfills all four goals of the NHLBI Strategic Vision by: a) elucidating a new exosomal aspect of human biology; b) reducing human disease by new therapeutic development against the exosomal pathway; c) developing a work force and an animal model exosome resource and; d) translating the exosome research to human disease.
项目总结

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 }}

J Edwin Blalock其他文献

J Edwin Blalock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('J Edwin Blalock', 18)}}的其他基金

A Novel Exosomal Inflammatory Pathway
一种新的外泌体炎症途径
  • 批准号:
    10540601
  • 财政年份:
    2017
  • 资助金额:
    $ 102.61万
  • 项目类别:
A Novel Exosomal Inflammatory Pathway
一种新的外泌体炎症途径
  • 批准号:
    10320741
  • 财政年份:
    2017
  • 资助金额:
    $ 102.61万
  • 项目类别:
A Novel Exosomal Inflammatory Pathway
一种新的外泌体炎症途径
  • 批准号:
    10541127
  • 财政年份:
    2017
  • 资助金额:
    $ 102.61万
  • 项目类别:
Genetics of Smoke-Altered LTA4H in COPD
COPD 中烟雾改变的 LTA4H 的遗传学
  • 批准号:
    9502350
  • 财政年份:
    2015
  • 资助金额:
    $ 102.61万
  • 项目类别:
Genetics of Smoke-Altered LTA4H in COPD
COPD 中烟雾改变的 LTA4H 的遗传学
  • 批准号:
    9281903
  • 财政年份:
    2015
  • 资助金额:
    $ 102.61万
  • 项目类别:
Acquired LTA4H Dysfunction in COPD
COPD 患者获得性 LTA4H 功能障碍
  • 批准号:
    8366816
  • 财政年份:
    2012
  • 资助金额:
    $ 102.61万
  • 项目类别:
Acquired LTA4H Dysfunction in COPD
COPD 患者获得性 LTA4H 功能障碍
  • 批准号:
    8857226
  • 财政年份:
    2012
  • 资助金额:
    $ 102.61万
  • 项目类别:
PGP, A Possible Biomarker for COPD Exacerbations and or Progression
PGP,COPD 恶化和/或进展的可能生物标志物
  • 批准号:
    8881993
  • 财政年份:
    2012
  • 资助金额:
    $ 102.61万
  • 项目类别:
Acquired LTA4H Dysfunction in COPD
COPD 患者获得性 LTA4H 功能障碍
  • 批准号:
    8515516
  • 财政年份:
    2012
  • 资助金额:
    $ 102.61万
  • 项目类别:
PGP, A Possible Biomarker for COPD Exacerbations and or Progression
PGP,COPD 恶化和/或进展的可能生物标志物
  • 批准号:
    8334299
  • 财政年份:
    2012
  • 资助金额:
    $ 102.61万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 102.61万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了