Aberrant Epigenetic Control of Notch Signals in Medulloblastoma

Jean-Francois Rual, Ph.D. University of Michigan

Progress Update from 1st year: 8/1/2014-7/30/2016

Millions of cells are formed every day in the developing brain of children. Medulloblastoma, the most common and ag-gressive form of pediatric brain tumor, occurs when the proliferation of cells in the cerebellum becomes uncontrolled, The Notch path-way is a key mechanism that governs cell proliferation in many bio-logical contexts. Aberrant up-regulation of Notch signals is associ-ated with medulloblastoma. Re-gaining control of Notch could help cure medulloblastoma patients. The goal of the Rual laboratory is to better understand the molecular mechanisms that control Notch signals in brain cells and to define novel therapeutic targets for the benefit of medulloblastoma patients. Using our proteomic platform, we discovered an interaction between RBPJ, a co-factor of Notch, and the product of a putative Polycomb group gene which is mutated in medulloblastoma. With the support for the CBTF Foun-dation, we propose to characterize the role of this interaction during medulloblastoma tumorigenesis. Our project will offer critical mechanistic insights that could be harnessed in the future for the therapeutic benefit of medulloblastoma patients. The Rual Lab is grateful to the Childhood Brain Tumor Foundation and the donors for their support for research.

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