Pilot Award Program

Targeting the YAP1/TAZ Pathway in Uveal Melanoma

Claudia Capparelli, PhD, aims to utilize bioinformatics, molecular approaches, and novel drugs with the ultimate goal of improving and devising new therapeutic options. Unlike cutaneous melanoma, metastatic uveal melanoma (UM) responds poorly to targeted therapies, including MEK inhibitors (MEKi). Additionally, UM frequently does not respond to immune checkpoint inhibitors (ICi). Despite the recent FDA approval of Tebentafusp, there remains an urgent need for effective therapeutic strategies to treat late-stage UM.

Dr. Capparelli’s aim is to improve the response of UM to targeted therapy and immunotherapy. This research would identify ways to attract immune cells to UM, making it more responsive to immune therapies.

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Uncovering Strategies to Improve the Efficacy of Targeted Therapy and Immunotherapies in BAP1-deficient UM

Vivian Chua, PhD’s research focuses on strategies to improve the effectiveness of targeted therapy to treat uveal melanoma. This investigation will perform a gene expression screening method to investigate differences in the genetic profiles of BAP1-deficient and BAP1-proficient uveal melanoma cells when treated with MEK inhibitors. The study will also identify whether these cells differentially alter the levels of proteins involved in inflammation which can affect interactions between the immune system and tumor cells. This research aims to uncover mechanisms that may be exploited to improve the responses of uveal melanoma cells to MEK inhibitors and immunotherapy.

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Improving Pre-clinical Uveal Melanoma Model Systems

There are currently no appropriate uveal melanoma animal models, hindering immune-based drug development. Ed Hartsough, PhD’s investigation will create uveal melanoma cell lines which mimic the human disease from the eyes of a common laboratory mouse strain. The resulting uveal melanoma cell lines can be introduced back into the mice without immune rejection which would allow for further immune-based studies. Through this research, Dr. Hartsough aims to create a uveal melanoma platform that can be utilized to model the effectiveness of immunotherapeutic approaches, which is critical in creating new treatments.

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Geospatial Distribution of Uveal Melanoma

Rino S. Seedor, MD, is investigating geospatial accumulations of uveal melanoma across the United States to determine if there are more uveal melanoma patients than expected in particular parts of the country at a particular time. The ultimate goal is to gain a better understanding of what causes uveal melanoma and the potential means to prevent it.

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Developing Molecular Tools for Targeted Degradation of Mutant GNAQ/11

Philip Wedegaertner, PhD’s investigation focuses on two common mutations in uveal melanoma—GNAQ and GNA11. Dr. Wedegaertner hopes to establish and drive research into the development of molecular tools and cell models to induce the destruction of the uveal melanoma-promoting mutants. The result of this research would help prevent tumor growth and the spread of uveal melanoma, which would greatly impact patients.

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