The studies in this application are designed to investigate the role of PTEN, a phosphatase about which very little is known in the lung. Deleted in many human cancers, Pten was initially thought to be a cancer suppressor gene. Its stellar role however, has emerged only recently as a key regulator of Progenitor/Stem cell homeostasis in various tissues including the brain and the gut. Preliminary data in this application show that epithelial deletion of Pten using a novel Nkx2.1-cre leads to expansion of the cells within the bronchioalveolar duct junction BADJ, a known lung Progenitor/Stem cell niche. Based on this finding future studies will be based on the HYPOTHESIS that "Pten regulates the pool of lung Progenitor/Stem cell population residing within the BADJ niche".
Three Specific Aims will test the hypothesis.
Specific Aim 1. To Characterize Functional Properties of Pten(d/d) Epithelial Cells.
Specific Aim 2. To Determine the Role of AKT and ?-Catenin in the Ptend/d lung Phenotype Specific Aim 3. To Determine the Role of Pten in the Lung Mesenchyme:
These Specific Aims represent a thorough and mechanistic analysis of the functional role of Pten in the lung and one of its disorders, pulmonary fibrosis.

Public Health Relevance

This is a proposal to study a gene named Pten which controls the number of Progenitor/Stem cells in the lung. The studies address the specific role of Pten in a serious lung condition known as Pulmonary Fibrosis for which no treatment currently exists other than transplantation. The long-term goal of this project is to learn enough about Pten to be able to modify its function and therefore prevent or treat lung disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-RES-B (02))
Program Officer
Lin, Sara
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University of Southern California
Schools of Medicine
Los Angeles
United States
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