Squamous cell carcinomas (SCC) collectively are the most common ectodermal cancers, resulting in >300,000 deaths per year. SCCs arise from renewable squamous epithelial cells that serve to create a barrier to the external environment in the skin, esophagus, lung and cervix. An early feature of squamous neoplasia is disruption of programmed differentiation, typically associated with thickening of the epithelium and increased proliferation. My laboratory focuses primarily on cutaneous SCC (cSCC) which is the most frequent skin cancer with malignant potential and contributes to greater than 1 in 4 skin cancer deaths in Caucasian populations. Patient groups with a high propensity to develop these tumors face a significant risk of mortality. One such group is the genetic skin blistering condition recessive dystrophic epidermolysis bullosa (RDEB) which is a devastating disease caused by mutations in a single gene, COL7A1. COL7A1 encodes for a protein called type VII collagen that forms connective fibrils linking the outer layer of the skin to the underlying tissue. My laboratory has a long standing interesting in trying to understand why mutations in this single gene lead to frequent and multiple life-threatening skin cancers.