The lab is focused on basic and biomedical aspects of lung injury and matrix remodeling. Prior work interrogated the role of proteolytic systems involved in this process, especially the urokinase receptor and endosomal cysteine proteases. These studies of the interface between cells and their matrix led to our recent emphasis on mechanisms underlying epithelial cell plasticity. We have developed in vivo fate mapping systems to track lung epithelial cells and discovered that epithelial mesenchymal transition (EMT) is a prominent feature of pulmonary fibrosis in several experimental models. Currently, the lab has projects on three aspects of EMT in the lung. The first is an approach to elucidating the important cell signaling pathways underlying EMT. We have developed conditional knockouts of several integrin receptors in lung epithelial cells and discovered altered TGF b 1 signaling and EMT in vivo in these mice. We are using these phenotypes as a starting point to dissect the specific role of integrin signaling in regulating EMT. Secondly, we want to define to what degree EMT contributes to human lung fibrosis and what drives EMT in the untreatable forms of this disease. Finally, because of the similarities between EMT in matrix remodeling and in cancer invasion and metastasis, we are exploring the signaling similarities between TGF b 1-driven EMT in fibrosis and oncogene and TGF b 1-mediated EMT in lung cancer. More detailed descriptions of current projects related to EMT and lung cancer, current lab members, and recent publications, are provided within the website ( pulmonary.ucsf.edu/chapmanlab).