Grant Award Details

Modulation of human alveolar stem cells to promote lung regeneration and avoid pulmonary fibrosis
Grant Number: 
DISC0-13788
Project Objective: 
  • The objective is to explore possible mechanisms of fibrotic lung disease, testing a hypothesis that changes to AT2 cells or their niche related to aging can negatively impact their regenerative potential. Lung organoid models will be used and sc-RNA-seq data will be generated.
Investigator: 
Disease Focus: 
Lung Disease, Fibrosis
Respiratory Disorders
Human Stem Cell Use: 
Adult Stem Cell
Award Value: 
$1,626,001
Status: 
Active

Grant Application Details

Application Title: 
  • Modulation of human alveolar stem cells to promote lung regeneration and avoid pulmonary fibrosis
Public Abstract: 

Research Objective

Understanding regulators of human alveolar lung stem cell function will promote more normal lung regeneration after injury and avoid the nearly untreatable problem of advanced pulmonary fibrosis.

Impact

Idiopathic Pulmonary Fibrosis (IPF), Adult Respiratory Distress Syndrome (ARDS), and other chronic fibrotic lung disorders.

Major Proposed Activities

  • Modify human fibroblasts to create a supporting niche promoting normal alveolar stem cell differentiation in ex vivo organoids, a model of stem cell/fibroblast crosstalk prominent in injured lungs.
  • Develop an in vivo co-transplantation model of human lung stem cells plus stem cell promoting fibroblasts for better engraftments and expansion in injured lungs of immunocompromised mice.
  • Elucidate signaling pathways necessary to reverse or prevent the pro-fibrotic effects of abnormal human lung stem cell function prominent in the pathobiology of fibrotic lung diseases.
Statement of Benefit to California: 

This application is focused on a set of lung diseases that are difficult to treat and associated with significant morbidity and mortality for citizens of California. The risk factors include advancing age, smoking, and exposure to inhalants that damage the lung. They all ultimately produce chronic scarring that impairs lung function. The goal of this research is to improve lung stem function which we believe will promote better lung regeneration after injury and attenuate scarring.