Our laboratory focuses on lung developmental biology, stem cell biology, and Regenerative Medicine and its application to human lung disease. We have already deciphered the role of Notch and Wnt signaling in embryonic lung development and human airway epithelial cells. These inquiries into the molecular mechanisms underlying adult lung epithelial regeneration and lung development will serve as a framework within which we seek to understand how the reactivation and distortion of normal developmental processes results in human lung diseases. In addition, we are examining the role of cellular plasticity and dedifferentiation in the airway epithelium in vivo using diphtheria toxin-mediated cell ablation. We are also the first group to have converted induced-pluripotent stem cells into human airway epithelium. Furthermore our iPS cells were derived using skin fibroblasts obtained from Cystic Fibrosis patients. Thus, we have developed the first tractable human platform for the dissection of a human lung disease. We are now developing assays that will be suitable for both large scale therapeutic screening and mechanistic investigations that will require large quantities of human airway epithelial cells. Finally, we are creating in vivo physiologically relevant models of human lung disease by generating mice with a humanized airway in which we can test the function and physiology of engraftable stem cell populations into the airway.