Grant: Operating Grant

Uveal melanoma, a malignancy of the uveal tract of the eye, is a highly aggressive cancer without any effective treatment options once it metastasizes. It represents the most common intraocular malignancy in North America and has a five year disease specific survival rate of ~80%. We have found that the majority of uveal melanomas have a mutation in one of two closely related genes, GNAQ or GNA11. In this application, we propose to study how mutations in GNAQ cause uveal melanoma. We have made a mouse model expressing the oncogenic form of GNAQ. These mice develop uveal melanomas and lung metastases, which are frequently observed in uveal melanoma patients. In this project, we will investigate the role of Nf1 in the GNAQ signaling pathway, determine mechanisms that allow melanocytes to naturally resist the effects of oncogenic mutations in GNAQ and GNA11, and seek new routes to uveal melanoma oncogenesis. These studies will help us to develop new therapies for uveal melanoma, a dreadful disease.