My research program is focused on understanding airway regeneration and lung stem cell biology.  We explore topics in fundamental stem cell biology such as size regulation, stem cell maintenance and regulation, metaplasia, epithelial organization, cell fate determination, axis formation, and cellular plasticity using the mammalian airway as a model system.  We are also particularly interested in learning how the abnormal activation of developmental pathways contributes to human lung disease and specifically to the process of metaplasia as it relates to cancer. Additionally, we are actively pursuing methods to generate actual human models of disease by growing human airway stem cells ex vivo, creating humanized mouse models of disease, using human airway explants, and creating patient-specific airway epithelium from induced-pluripotent stem cells. We are using Cystic Fibrosis, asthma, COPD, lung fibrosis, and lung cancer as entry points into our exploration of creating human model systems.  We collaborate extensively with experts in novel imaging modalities, epigenetics, and computational biology to name a few.   

In the past 4 years, our laboratory has been the first to create human airway epithelium from patient-specific induced-pluripotent stem cells (Cell Stem Cell), the first to demonstrate a new form of stem cell regulation known as feed-forward regulation in which stem cells act as niches for their own daughters (Nature), and the first to show that a mature vertebrate cell can dedifferentiate and become a stable stem cell following injury (Nature).  We have also identified that stem cells of the airway are more heterogeneous than originally thought (Cell Stem Cell), that Yap is an essential regulator of stem cell identity itself (Developmental Cell), and a new protocol that allows for long term expansion of stem cells from diverse organs allowing new avenues in disease modeling and tissue biology (Cell Stem Cell).