This Program Project Grant application is founded on the hypothesis that during lung injury, recovery of alveolar epithelial cell function is of crucial importance in the prevention of disordered healing, fibrosis and thus the outcome of patients with the acute respiratory distress syndrome (ARDS). We have assembled a highly interactive group of investigators who have worked collaboratively, productively and synergistically in the previous cycle of the grant. We propose to study alveolar epithelial cell injury and repair via three interrelated projects and three supportive cores. In Project # 1 we will focus on the mechanisms regulating alveolar epithelial function during hypoxia as it pertains to Na,K-ATPase phosphorylation-endocytosis and ubiquitination-degradation. In Project # 2 we will determine the role of intermediate filaments in alveolar epithelial wound repair and remodeling. In Project # 3 we will investigate the mechanisms of alveolar epithelial apoptosis in the development of lung injury and repair. Collaborative studies have been conducted for each of the projects and the preliminary results support the feasibility of this proposal. This Program Project focuses the multidisciplinary expertise of the investigators on the elucidation of mechanisms contributing to lung epithelial cell injury in clinically relevant models of injury. These projects are interactive conceptually and programmatically, where the aggregate of the projects is greater than the sum of its parts. Their collective outcome will provide a composite picture of the regulation of the Na,K-ATPase and intermediate filaments in the alveolar epithelium during injury and determine the role of alveolar epithelial cell apoptosis in the pathogenesis of lung injury. The insights gained from the data generated from these studies will provide novel molecular targets for the development of new therapeutic strategies to treat patients with lung injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL071643-09
Application #
8255576
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Harabin, Andrea L
Project Start
2002-12-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
9
Fiscal Year
2012
Total Cost
$2,127,247
Indirect Cost
$732,331
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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