The effort of our laboratory is to identify fundamental mechanisms that are responsible for abnormalities of the airway epithelial cell differentiation in chronic lung disease. We seek to identify the genetic and acquired defects that are responsible for the pathology and symptoms of airway diseases including chronic obstructive pulmonary diseases (COPD), asthma, bronchitis, bronchiectasis, respiratory virus infection and chronic bacterial infection. Studies concern each of the specific cell types in the airway, stem cells, ciliated and secretory cells and their relationship to lung disease. To accomplish these studies we are using human tissues, cultured human and mouse airway epithelial cells and mouse models.