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Essential Role of The Cyclin G-Associated Kinase (GAK) In Diffuse Large B-Cell Lymphoma Mitotic Progression
Location: 39
Mentor: Ms. Olivia Lightfuss
Diffuse Large B Cell Lymphoma (DLBCL) is the most commonly diagnosed hematologic malignancy in the United States. Up to 40% of patients remain uncured by the current standard care immunochemotherapy. There is a critical need to identify novel targeted therapies to improve patient outcomes. The lab conducted a phenotypic screen of kinase inhibitors followed by a machine learning based analysis against DLBCL cell lines and non-malignant peripheral blood mononuclear cells (PBMCs) controls. The screen identified the cyclin G-associated kinase (GAK) as a tumor-selective, readily druggable target whose inhibition killed DLBCL cells while sparing PBMCs. GAK is a previously unstudied kinase that, when inhibited, has a potent effect in arresting the cell cycle, specifically in M phase. Additionally, it has been established that GAK loss-of-function is a synthetic lethal vulnerability in systems with inactivation of the master cell-cycle regulator, retinoblastoma-associated protein (RB) encoded by RB1. Defining the association between RB and GAK will prove critical to finding more effective therapies linked to specific biomarkers for cancer patients. The main objective is to investigate any links present between RB levels in cells and GAK inhibitions.
