Our laboratory uses the skin to answer unresolved questions in stem cell biology, cancer genetics and metastasis, and signaling. We aim to use our discoveries to develop novel cellular and molecular therapies for epithelial diseases. In the process, our goal is to train the brightest and most promising scientists using the newest stem cell, genomic, and bioinformatic approaches.  We have focused recently on the role of Sonic hedgehog (Shh) signaling pathway and how it contributes to skin and hair development.  We have established the connection between Shh and human cancer (1997)  basal cell carcinoma of the skin. Recent studies from our lab and others suggest three important areas for tumor progression: activation of the Shh pathway in the epithelium, generation of mutations that confer growth advantage, and the presence of a permissive tumor stroma. We have been focused on how the tumor stroma impinges on Shh signaling in the epithelium. Our studies should lead to an understanding of tumor-stroma interactions in other epithelial cancers and well as during normal tissue regeneration. More recently the lab has focused on developing cell based therapies for genetic skin diseases using autologous, CRISPR-corrected iPS-derived skin grafts. We have defined the chromatin dynamics during skin differentiation that have led to improved in-process manufacturing markers and more efficient tissue stem cell production. These studies underlie the Center for Definitive and Curative Medicine, "one dose is a cure", for the treatment of genetic diseases.