Growth and/or Recruitment of a Novel Cell Population with Neural Crest Origin in Lung Fibrosis
Abstract
This research project will address the Topic Area, “Pulmonary Fibrosis.” Lung fibrosis is a progressive disease with excessive scarring in the lung, resulting in loss of respiratory function and death. It has been recognized that US military Service member and Veterans may be at increased risk of developing lung fibrosis as a consequence of additional deployment-associated inhalation exposures, e.g., burn pit smoke and desert sand dust. Therefore, lung fibrosis research is highly relevant to the missions of Congressionally Directed Medical Research Programs. Lung fibroblasts and myofibroblasts are the key cells that are increased in fibrosis lung and directly involved in scaring formation. The mechanisms for abnormal increase of these cells in lung fibrosis, such as where they come from, and how they grow and produce scar materials, are not clear. Lack of such knowledge creates a hurdle to develop effective treatment to stop the disease progression. We have proposed a research plan to study a new origin of these fibroblasts/myofibroblasts and related mechanisms in contributing to lung fibrosis using mouse lung fibrosis models. State-of-the-art genetic technology will be used to mark the cell population of interests, called neural crest-derived cells. Therefore, whether these cells are increased in circulation and recruited to fibrosis lung and become scar-producing cells will be determined at different stages of lung fibrosis. This research project will be new in many aspects, such as using new genetically manipulated mice to label a defined cell population in lung fibrosis research, generating a concept regarding a new previously unidentified origin of lung fibroblasts and myofibroblasts in contributing to fibrosis progression, exploring a new mechanism for abnormal fibroblast/myofibroblast accumulation in fibrosis lung, etc. This is a high-risk and potentially high-reward research project. This study will also lay the groundwork for developing future breakthrough research in lung fibrosis patients. We believe that this work will ultimately contribute to improved health outcomes for pulmonary fibrosis patients through providing new knowledge to develop innovative therapeutic strategies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810185
Entities
People
- Wei Shi
Organizations
- United States Army