David E. Fisher, M.D., Ph.D.

Research

The Fisher Lab studies cell death and proliferation signals in relation to development and disease, particularly cancer. We attempt to understand critical modes of cell homeostasis with a goal of molecular targeted therapy for human disease. We have three main focuses at this time. We study apoptosis in p53 wild type or deficient tumor cells containing defined oncogenes. We have identified a transcriptional network which regulates melanoma cell survival and proliferation as well as melanocyte differentiation during development. Using diverse methods including mouse models, human tumor expression arrays, and cellular assays, we examine mechanisms through which melanoma cells evade death, with the goal of improving therapy. These studies also include examination of the role of UV in melanocyte biology and carcinogenesis. We also are looking at Mitf which is a helix-loop-helix factor homologous to Myc, whose mutation produces absence of melanocytes and severe abnormalities in osteoclasts, the cells responsible for bone mineral re-absorption. Mitf mutations occur in humans with Waardenburg Syndrome, a condition involving pigmentation and deafness. Mitf acts as a master regulator of melanocyte and osteoclast development and is targeted by several critical signaling pathways.