Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers

项目摘要/摘要 吸烟是已知的导致肺部疾病的最大单一风险因素，是一种 发展为肺气肿和特发性肺纤维化的主要风险。我们有 组建了一组调查人员，他们协同工作，更好地了解了机制(S) 香烟烟雾可导致肺纤维化或肺气肿。我们的团队成员是 COPD和IPF领域最致力于更好地理解其机制(S) 香烟烟雾可导致肺纤维化或肺气肿的表型。在上一次 P01 HL114501基金“不同和重叠的纤维化途径”资助多年 和吸烟者的肺气肿“，我们整合了慢性阻塞性肺病研究人员的专业知识 和IPF社区，跨越基础、翻译和临床研究人员，聚集在一起解决这一问题 这是一个重要的挑战。项目和核心之间的这种协同整合已经产生了影响，并将 继续大于它的每个组成部分的总和。我们雇佣了优约主义者和 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Udiscovery 利用高通量图谱(基因组学、表观遗传学)方法在人肺组织和 细胞(项目3)发现介导卷烟纤维化和肺气肿表型的新途径(S) 吸烟者。因此，PPG机制不仅是关键的，而且是绝对必要的，以最好地解决 手头这个根本问题的主要目标是：我们如何才能更好地理解机制(S) 哪种香烟烟雾引起肺纤维化或肺气肿表型？我们将尝试与 我们的目标由以下U项目和核心中描述的方法实现： 项目： 1)COPD和IPF的线粒体和代谢功能障碍 CHI3L1及其受体在肺纤维化和COPD中的不同作用 3)在COPD和IPF中整合OMICS、网络和功能研究 核心： A)行政核心 B)呼吸计算发现核心 C)临床生物信息库核心 D)分子表征核心

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