My laboratory studies uveal melanoma (UM), which is the most common primary tumor in the eyes of adults. Metastatic UM remains one of the deadliest cancers, is notoriously hard to treat, and forms almost uniformly lethal metastasis. New treatment angles are urgently needed. We have worked on deciphering the roles of the driver mutations in GNAQ and BAP1, describing their impact on cellular transformation, immune modulation, and the epigenetic changes promoting a metastatic phenotype. A major focus currently is to decipher the role of PRAME expression in UM, which we have shown to correlate significantly with patient outcomes. We found that PRAME induces genomic instability, potentially allowing for adaptive tumor evolution. Major goals of this project are to characterize the epigenetic changes occurring when PRAME is expressed, as well as identifying new drugs to target metastatic UM. We are also conducting larger drug screens to identify novel compounds that we might can utilize clinically. Using this approach, we have recently identified several novel lead compounds which are being tested in animal models, and are hoping that we can initiate more clinical trials in near future.

We are also investigating retinoblastoma (Rb), the most common childhood cancer in the eye. While treatable in many cases in developed countries, the eyes of infants and children still have to be removed frequently. There are no specific treatments for Rb. We are aiming to understand the epigenetic drivers leading to optic nerve invasion, which correlates with high mortality. We are also screening compounds to target Rb more specifically.

Further, as part of the Interdisciplinary Stem Cell Institute (ISCI), our lab also forms the ISCI pluripotent stem cell incubator, which serves as a multi-disciplinary platform to collaborate on the development of various organoid models. One of the main projects currently is utilizing induced pluripotent stem cells (iPSCs) to generate forebrain organoids as a model for the metastatic spread of retinoblastoma. Using micro-injections, retinoblastoma cells are injected into these organoids to track growth and spread.