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 #
5P01HL114501-05
Application #
9300997
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Punturieri, Antonello
Project Start
2013-09-06
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2019-06-30
Support Year
5
Fiscal Year
2017
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
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