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. While pulmonary fibrosis and emphysema can co-exist in the same individual, our recent report indicates that subclinical idiopathic pulmonary fibrosis (IPF) is inversely associated with total lung capacity and emphysema in smokers. Along with the fact that most former smokers with IPF do not have radiographic evidence of emphysema, suggests that these patterns of disease are likely to be due to distinct consequences of smoking reflecting unique individual susceptibilities, and its associated differential pathogenetic pathway(s). We have assembled a team of investigators who have worked efficiently and synergistically to better understand the mechanism(s) by which cigarette smoke can induce either fibrotic or emphysematous, or both phenotype. We have integrated the expertise of investigators from COPD and IPF community, both basic and translational, to come together to tackle this important challenge. The impact of reaching this major goal will be significant in the pulmonary community as we hope to unravel new molecular targets and/or treatment(s) for COPD and IPF. We will attempt to reach our goals by the addressing the following projects and cores: Projects: 1) Homeostatic Role of Autophagy in Lung Emphysema and Fibrosis 2) Genetic Modifiers of TGF-Beta1 and Cigarette Smoke in Fibrosis and Emphysema 3) Genetics and Epigenetics of COPD and IPF 4) Clinical Outcomes and Molecular Phenotypes in Smokers with Parenchymal Lung Disease Cores: 1) Administrative Core 2) Respiratory Computational Discovery Core 3) Clinical Biorepository Core 4) Murine Models and Molecular Analysis Core

Public Health Relevance

The pathogenesis of COPD and IPF is poorly understood. In this program project we have integrated the expertise of investigators from COPD and IPF community, both basic and translational, to come together to better understand the pathogenesis of these chronic lung diseases, and hopefully identify new molecular targets in the treatment of these dreadful diseases in the future.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
4P01HL114501-04
Application #
9113651
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Punturieri, Antonello
Project Start
2013-09-06
Project End
2018-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Lopes-Ramos, Camila M; Kuijjer, Marieke L; Ogino, Shuji et al. (2018) Gene Regulatory Network Analysis Identifies Sex-Linked Differences in Colon Cancer Drug Metabolism. Cancer Res 78:5538-5547
Morrow, Jarrett D; Glass, Kimberly; Cho, Michael H et al. (2018) Human Lung DNA Methylation Quantitative Trait Loci Colocalize with Chronic Obstructive Pulmonary Disease Genome-Wide Association Loci. Am J Respir Crit Care Med 197:1275-1284
Hong, J Y; Kim, M; Sol, I S et al. (2018) Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-? expression and Foxp3+ Treg cells. Allergy 73:1686-1699
Mizumura, Kenji; Justice, Matthew J; Schweitzer, Kelly S et al. (2018) Sphingolipid regulation of lung epithelial cell mitophagy and necroptosis during cigarette smoke exposure. FASEB J 32:1880-1890
Sharma, Amitabh; Kitsak, Maksim; Cho, Michael H et al. (2018) Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a COPD Disease Network Module. Sci Rep 8:14439
Ash, Samuel Y; Harmouche, Rola; Putman, Rachel K et al. (2018) Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers. Thorax 73:1071-1074
Axelsson, Gisli Thor; Putman, Rachel K; Araki, Tetsuro et al. (2018) Interstitial lung abnormalities and self-reported health and functional status. Thorax 73:884-886
Lee, Chang-Min; Cho, Soo Jung; Cho, Won-Kyung et al. (2018) Laminin ?1 is a genetic modifier of TGF-?1-stimulated pulmonary fibrosis. JCI Insight 3:
Ash, Samuel Y; Harmouche, Rola; Ross, James C et al. (2018) Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort. Radiology 288:600-609
Polverino, Francesca; Rojas-Quintero, Joselyn; Wang, Xiaoyun et al. (2018) A Disintegrin and Metalloproteinase Domain-8: A Novel Protective Proteinase in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 198:1254-1267

Showing the most recent 10 out of 100 publications