Year 3

Our research program seeks to identify reparative cells of the lung that contribute to normal maintenance and repaired after injury, determine how they are regulated at the molecular level, and to determine how and why these cells are disregulated in lungs of patients with chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Our long-term goal is to determine how lung disease is caused and use this information to develop new therapies that will prevent either initiation or progression of lung disease. We have made progress in studies using mouse models to investigate lung repair mechanisms and also with human samples to understand how lung tissue stem cells change in patients with lung disease. In animal studies we have defined cells that migrate within the lung to repair damage caused by severe H1N1 influenza virus infection. Over our last funding period we discovered that the immune response to viral infection plays an important role in changing epithelial cells to enhance repair of damage. This novel data could provide new ways of activating lung tissue repair mechanisms to promote lung regeneration. Our work with patient samples has allowed us to identify molecular signatures of normal lung cell types that line airspaces of the lung and molecular changes to these cells seen in IPF. We have developed mouse models to further explore disease mechanisms and are using these models to define potential therapeutic targets that may alter disease outcome. We have made significant progress in the development “lung in a dish” models for human cells and have established methods for the generation of lung cell types from patient-specific pluripotent cells (a type of stem cell that has the potential to generate all cells of the body). Continuation of this work will provide new model systems and a more comprehensive understanding of molecular changes to lung cells that accompany disease. This information will allow us to define new targets for drug development and opportunities to help patients with intractable lung diseases.