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
- 来源:
- 关键词:African AmericanAnimal ModelAnimalsAsianBiochemistryCardiologyCaucasiansCell DeathCellsCellular biologyChemistryChronicChronic Obstructive Pulmonary DiseaseDiseaseExtracellular MatrixExtracellular Matrix DegradationFacultyGoalsGrantHumanHuman BiologyImmuneInflammationLatinaLeukocyte ElastaseLungMedical StudentsMentorsMissionModelingMolecular BiologyMusNational Heart, Lung, and Blood InstitutePathogenicityPathway interactionsPatientsPeptide HydrolasesPhasePhenotypePhysiciansPhysiologyPostdoctoral FellowProtease InhibitorProtein Kinase InteractionRIPK1 geneResearchResistanceResourcesRoleScientistSmokerSmokingStrategic visionSurfaceTissuesTrainingTranslatingUnited States National Institutes of HealthWorkalpha 1-Antitrypsinchronic inflammatory diseasecigarette smoke-induceddisease phenotypedoctoral studentexosomeexposure to cigarette smokeextracellularextracellular vesicleshuman diseaseinnovationmembermouse modelmultidisciplinaryneutrophilnew therapeutic targetnovelnovel diagnosticsnovel therapeuticspathogenprogramstherapeutic development
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)
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J Edwin Blalock其他文献
J Edwin Blalock的其他文献
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{{ truncateString('J Edwin Blalock', 18)}}的其他基金
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:
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:
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:
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