South Lab

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 on SCC arising in the rare genetic skin blistering condition recessive dystrophic epidermolysis bullosa (RDEB), 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 stratifying epithelia to the underlying tissue. Unlike classical tumor suppressors such as TP53, BRCA1, and PTCH1, where heterozygous germline mutations predispose patients to develop multiple tumor types, COL7A1 mutation alone does not provide a selective advantage to tumor cells and somatic mutations are not reported in any cancer type profiled to date.

Current data indicate germline mutations in COL7A1 create a permissive tumor microenvironment driven by tissue damage because of skin fragility and highlight RDEB as a familial tumor prone disease driven by an altered microenvironment. My laboratory has a long standing interesting in trying to understand why mutations in this single gene lead to inevitable and life-threatening SCC. By comparing RDEB SCC with sporadic SCC arising in other tissues, such as the head and neck, we can work towards targeting pathomechanisms associated with aggressive disease across all squamous cancers.