Investigations of Cryab activity in gliomagenesis

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DESCRIPTION (provided by applicant): High-grade gliomas carry a grim prognosis. Current therapies only modestly prolong survival and therefore there is great interest in developing better, targeted therapies for glioma treatment. CRYAB has been identified as a candidate glioma oncogene as it is frequently over-expressed in human gliomas. Studies in established glioma cell lines have indicated a role for CRYAB in apoptosis and invasion, however the importance of CRYAB in glioma initiation and progression remains unclear due to a paucity of animal studies where potential effects of CRYAB on the immune system can also be modeled. The research proposed here will utilize mouse genetic models to investigate the impact of Cryab on gliomagenesis in an in vivo, immunocompetent, autochthonous setting. Specifically, the impact of genetic Cryab over-expression and loss on glioma formation in a glioma pre-disposed genetic background will be examined. The effect of Cryab over-expression on apoptosis rates and immune cell infiltration in vivo will be examined. These studies are expected to establish an oncogenic role of CRYAB in gliomagenesis and to provide the foundation for future studies to determine if CRYAB-modulating drugs may have utility as glioma targeted therapies.