J. William Harbour, M.D.

DEPARTMENT OF Ophthalmology & Visual Science
Keywords: cancer, cell cycle, gene expression profiling, tumor suppressors, transcriptional regulation

A major focus of our lab is the retinoblastoma (Rb) tumor suppressor pathway, which regulates cell cycle, differentiation, senescence and apoptosis. Rb is directly mutated or functionally inhibited in virtually all human cancer cells. Recently, we have shown using melanoma as a model system that terminal differentiation creates a selective pressure to mutate the Rb pathway to allow cells to re-enter the cell cycle, which may explain the strong tendency for melanomas to acquire mutations affecting the p16Ink4a tumor suppressor. Studies are underway to further understand the role of Rb in tumor suppression in melanoma.

The other major focus of the lab is the relationship between developmental lineage and tumor phenotype. We have identified a malignant switch that occurs during melanoma progression. This malignant switch is associated with regression to a primordial phenotype within the developmental lineage of melanocytes through a distinct mesenchymal to epithelial transition. Studies are underway to identify the molecular mechanisms of this malignant switch.