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Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers

吸烟者纤维化和肺气肿的独特和重叠途径

基本信息

批准号：
10172307
负责人：
Augustine M Choi
金额：
$ 265.88万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-06 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10172307
关键词：
Address Adherence Age Alveolar Macrophages Animal Model Binding Biological Bleomycin Bronchoscopy CHI3L1 gene Cell Culture Techniques Cells Chitinase Chronic Obstructive Airway Disease Chronic lung disease Cigarette Smoker Clinical Communities Data Data Reporting Development Disease Ensure Epigenetic Process Epithelial Cells Experimental Designs Exposure to Fibrosis Foundations Funding Future Gene Expression Genetic Genomics Goals Grant Hamman-Rich syndrome Hand Health Human Human Resources Image Institution Link Lung Lung diseases Mediating Metabolic Pathway Metabolic dysfunction Metadata Methods Mitochondria Mitochondrial DNA Modeling Modification Molecular Molecular Target Multiomic Data Mus PINK1 gene Pathogenesis Pathway Analysis Pathway interactions Phenotype Physiology Plasma Policies Poly I-C Process Protein Phosphatase 2A Regulatory Subunit PR53 Proteins Pulmonary Emphysema Pulmonary Fibrosis RIPK3 gene Regulator Genes Reporting Research Research Activity Research Personnel Resources Risk Risk Factors Role Sampling Severities Severity of illness Signal Transduction Site Smoker Spirometry Structure of parenchyma of lung Study models Sum Systems Analysis Technology Tissues Translating United States National Institutes of Health Validation Work airway epithelium biobank cigarette smoke cigarette smoking clinical Diagnosis cohort data management data sharing database of Genotypes and Phenotypes disease diagnosis exposure to cigarette smoke glycosylation human disease idiopathic pulmonary fibrosis lung development lung volume meetings member mitochondrial dysfunction mouse model programs receptor recruit respiratory response single-cell RNA sequencing trafficking transcriptome sequencing urinary

项目摘要

PROJECT SUMMARY/ ABSTRACT Cigarette smoking is the greatest known single risk factor for the development of lung disease, being a dominant risk for the development of both emphysema and idiopathic pulmonary fibrosis. We have assembled a team of investigators who have worked synergistically to better understand the mechanism(s) by which cigarette smoke can induce either lung fibrosis or emphysema. Our team members are leaders in the field of COPD and IPF who are most committed to better understand the mechanism(s) by which cigarette smoke can induce either fibrotic or emphysematous phenotype in the lung. During the previous years of funding support by P01 HL114501 grant entitled “Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers”, we have integrated the expertise of investigators from the COPD and IPF communities, spanning basic, translational and clinical researchers, to come together to tackle this important challenge. This synergistic integration among the projects and cores have been impactful and will continue to be greater than the sum of each of its component parts. We employ both Ureductionist and mechanisticU approaches by utilizing cell culture and animal models (Project 1 and Project 2), and UdiscoveryU approaches using high throughput profiling (genomics, epigenetics) methods in human lung tissues and cells (Project 3) to discover new pathway(s) mediating the fibrotic and emphysema phenotypes in cigarette smoker. Hence, a PPG mechanism has been not only critical but absolutely necessary to best address the main objective of this fundamental question at hand: How can we better understand the mechanism(s) by which cigarette smoke mediates fibrotic or emphysematous phenotype in the lung? We will attempt to reach our goals by approaches described in the following Uprojects and cores: Projects: 1) Mitochondrial and Metabolic Dysfunction in COPD and IPF 2) Differential roles of Chi3l1 and its Receptors in Pulmonary Fibrosis and COPD 3) Integrating Omics, Networks, and Functional Studies in COPD and IPF Cores: A) Administrative Core B) Respiratory Computational Discovery Core C) Clinical Biorepository Core D) Molecular Characterization Core

项目总结/摘要吸烟是已知的最大的单一危险因素的发展肺部疾病，是一个肺气肿和特发性肺纤维化的主要风险。我们有组建了一个调查小组，他们协同工作，以更好地了解机制香烟烟雾可诱发肺纤维化或肺气肿。我们的团队成员是领导者， COPD和IPF领域最致力于更好地了解香烟烟雾可在肺中诱导纤维化或肺气肿表型。前一 P01 HL 114501基金会多年的资金支持，题为“纤维化的独特和重叠途径” 和吸烟者肺气肿”，我们整合了COPD研究人员的专业知识，和IPF社区，包括基础、转化和临床研究人员，共同解决这一问题重要的挑战。项目和核心之间的这种协同整合具有影响力，仍然大于其每个组成部分的总和。我们既雇用了还原论者，利用细胞培养和动物模型的机械方法（项目1和项目2），以及UdiscoveryU 在人肺组织中使用高通量分析（基因组学、表观遗传学）方法的方法，细胞（项目3），以发现新的途径介导的纤维化和肺气肿的表型，在香烟吸烟者。因此，按项目付费机制不仅至关重要，而且绝对有必要最好地解决这一问题。当前这一基本问题的主要目标是：我们如何通过以下方式更好地理解机制：哪种香烟烟雾介导肺部纤维化或肺气肿表型？我们将尝试我们的目标通过以下U项目和核心中描述的方法实现：项目： 1)COPD和IPF患者的线粒体和代谢功能障碍 2)Chi 3l 1及其受体在肺纤维化和COPD中的作用 3)整合COPD和IPF的组学、网络和功能研究核心： A.行政核心 B）呼吸计算发现核心 C）临床生物储存核心 D）分子表征核心