Washington University in St. Louis

Dr. Michael Onken receives ACS Institutional Research Grant.

Congratulations to Mike for receiving a one-year American Cancer Society Institutional Research Grant from the Siteman Cancer Center!

Project Title:  "Identifying the Genomic Targets of BAP1 in Uveal Melanoma"
Award Period:  1/01/15 - 12/31/15

Summary:  Uveal melanoma (UM) is a highly metastatic form of cancer that spreads to distant organs in almost half of patients, with a lethal outcome. Metastasis is linked to mutations of BAP1, which is inactivated in primary tumors that spread out of the eye. BAP1 is an enzyme that regulates the expression of target genes. Despite the strong clinical link between BAP1 and melanoma mortality, little is known about the biological function of BAP1 in melanoma, including the identity of its target genes in UM cells. The long-term goal of this research is identify the pathways and mechanisms that link BAP1 to UM spread. To this end, the specific aims of this proposal are: 1) Map the targets of BAP1 in UM using genomic “calling cards,” a novel methodology, and 2) Identify BAP1 targets that help UM cells enter and exit the bloodstream. In collaboration with Dr. Robi Mitra, Dr. Onken created a BAP1 fusion protein, which inserts DNA “calling cards” into chromosomes wherever BAP1 binds. Next-Gen sequencing will identify these regions, and Dr. Onken will identify the genes most likely to be involved in metastatic spread.  Working with John Cooper's lab, he  has developed a novel cell-based system that models the migration of tumor cells across blood vessels. He will use this model system to connect the targets of BAP1 to the spread through the bloodstream. BAP1 mutations have been found in other cancers, and this project will identify new therapeutic targets for treating patients with advanced disease.

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