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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：
10636890
负责人：
Augustine M Choi
金额：
$ 255.39万
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/10636890
关键词：
Address Adherence Age Airway Fibrosis Alveolar Macrophages Animal Model Binding Biological Bleomycin Bronchoscopy CHI3L1 gene Cell Culture Techniques Cells Chitinase Chronic Obstructive Pulmonary 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 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 Probability Process Protein Phosphatase 2A Regulatory Subunit PR53 Proteins Pulmonary Emphysema Pulmonary Fibrosis RIPK3 gene 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 Usual Interstitial Pneumonia 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 gene regulatory network 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

项目概要/摘要吸烟是导致肺部疾病的最大已知单一危险因素，发生肺气肿和特发性肺纤维化的主要风险。我们有组建了一个研究小组，他们协同工作以更好地理解机制香烟烟雾可诱发肺纤维化或肺气肿。我们的团队成员是以下领域的领导者 COPD 和 IPF 领域最致力于更好地了解其机制的人香烟烟雾可诱发肺部纤维化或肺气肿表型。此前期间题为“纤维化的不同和重叠途径”的 P01 HL114501 拨款提供了多年的资助和吸烟者的肺气肿”，我们整合了 COPD 研究人员的专业知识和 IPF 社区，涵盖基础研究人员、转化研究人员和临床研究人员，齐心协力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，并将继续大于其各个组成部分的总和。我们同时雇用 Ureductionist 和利用细胞培养和动物模型（项目 1 和项目 2）和 UdiscoveryU 的机制方法在人类肺组织中使用高通量分析（基因组学、表观遗传学）方法和细胞（项目 3）发现介导香烟纤维化和肺气肿表型的新途径吸烟者。因此，PPG 机制对于最好地解决这一问题不仅至关重要，而且绝对必要。当前这个基本问题的主要目标是：我们如何更好地理解机制哪种香烟烟雾会介导肺部纤维化或肺气肿表型？我们将努力达到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 中的线粒体和代谢功能障碍 2) Chi3l1及其受体在肺纤维化和COPD中的不同作用 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) 临床生物样本库核心 D) 分子表征核心

项目成果

期刊论文数量（105）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Applying Functional Genomics to Chronic Obstructive Pulmonary Disease.

DOI：
10.1513/annalsats.201808-530mg
发表时间：
2018-12
期刊：
Annals of the American Thoracic Society
影响因子：
8.3
作者：
E. Silverman
通讯作者：
E. Silverman

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

DOI：
10.1002/gepi.21979
发表时间：
2016-09
期刊：
Genetic epidemiology
影响因子：
2.1
作者：
Choi S;Lee S;Qiao D;Hardin M;Cho MH;Silverman EK;Park T;Won S
通讯作者：
Won S

Host chitinase 3-like-1 is a universal therapeutic target for SARS-CoV-2 viral variants in COVID-19.

DOI：
10.7554/elife.78273
发表时间：
2022-06-23
期刊：
ELIFE
影响因子：
7.7
作者：
Kamle, Suchitra;Ma, Bing;Lee, Chang Min;Schor, Gail;Zhou, Yang;Lee, Chun Geun;Elias, Jack A
通讯作者：
Elias, Jack A

Automated measurement of pulmonary emphysema and small airway remodeling in cigarette smoke-exposed mice.