The proposed studies will use innovative approaches to expand upon our knowledge of lung stem cells to broaden treatment paradigms for NHLBI-related lung diseases. We therefore hypothesize that the maintenance of lung MSC function by Wnt/?-catenin signaling is necessary for pulmonary tissue homeostasis. We propose to examine lung MSC-dependent mechanisms of abnormal pulmonary architecture and function using novel mouse models both in vitro and in vivo. We will determine the mechanism by which adult lung MSCs contribute to pulmonary tissue architecture and function in vivo. In addition, we will determine the mechanism by which Wnt/?-catenin signaling regulates lung MSCs function and affects tissue homeostasis using both in vitro and in vivo novel systems. These models will enable us to identify a cell type which may be suited as a therapeutic target. Additionally, these studies will generate important resources and reagents that will be of vast interest to both the scientific and medical communities.

Public Health Relevance

Changes in tissue structure associated with COPD are due in part to cell death resulting in enlarged airspaces and loss of alveolar capillary endothelium and vascular dysfunction. The diverse pathologies of lung diseases demand that therapeutic interventions target mechanisms controlling the regenerative capacity of distinct lung compartments. Therefore, the goal of our studies is to identify the mechanisms that regulate the lung mesenchymal stem cell (MSC) compartment in the distal lung. Understanding the afore mentioned processes are crucial to our knowledge of the role lung MSC play in the maintenance of pulmonary tissue structure and function as well as the identification of directed therapies targeting this specific compartment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL116597-01A1
Application #
8599945
Study Section
Special Emphasis Panel (ZRG1-CVRS-G (04))
Program Officer
Punturieri, Antonello
Project Start
2013-08-01
Project End
2017-05-31
Budget Start
2013-08-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$518,687
Indirect Cost
$160,369
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Majka, Susan M; Miller, Heidi L; Helm, Karen M et al. (2014) Analysis and isolation of adipocytes by flow cytometry. Methods Enzymol 537:281-96