Grant: Travel Awards - Institute Community Support

Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults. The disease arises from melanocytes of the uveal tract, which includes the iris, ciliary body, and choroid. The incidence rate is around 5.1 per million in the U.S. However, despite being a relatively rare disease, it is nevertheless deadly since about 50% of UM patients will develop metastasis (usually to the liver), and there are currently no effective treatment for metastasized UM. Interestingly, over 83% of UM has the mutation in a family of G proteins called GNAQ or GNA11. These mutations happen in a mutually exclusive way, and are believed to be the early or initiating mutations in UM. The first objective of my project is to characterize GNAQ-mutated melanocytes. I would be establishing primary human melanocytes from donor eyes, and then proceeding with a lentiviral transduction to create GNAQ-mutant and wild type transduced melanocytes. The cells would then be characterized through functional assays of proliferation, migration, and invasion levels. Additionally, quantitative proteomic profiles will be obtained through mass spectrometry for the different cells, to hopefully reveal key mediators in the development of UM. It is believed that GNAQ/11 mutations act as the initiating events, but another set of events are required for melanocytes to developing malignancy. Therefore the second objective of my project is to try to verify the identity of a second oncogenic hit in addition to GNAQ mutation needed for the development of UM. We propose blue light to be a candidate for this second hit. Several papers have demonstrated an implication of blue light in UM, showing that blue light exposure increased proliferative potential of cells. We hypothesize that GNAQ-mutant melanocytes after blue light exposure would become just as proliferative, migrative, and invasive as UM cell lines, thus confirming if blue light acts as the transforming event.