To expand on pathways driving glioblastoma (GBM) and create new routes for therapy, my lab has been focusing on oncogenic RNA binding proteins (RBPs). RBPs are critical regulators of gene expression and are often altered in cancer. We have identified SERBP1 (Serpine RNA binding protein 1) as a novel oncogenic RBP in GBM. SERBP1 high expression correlates with poor patient prognosis and influences treatment response. We established that SERBP1 regulates critical metabolic routes (One Carbon, Methyl and MTA cycles) and this regulation leads to activation of cell cycle, tumor growth, proliferation of glioma stem cells and silencing of genes implicated in neuronal differentiation. Our study has ...

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To expand on pathways driving glioblastoma (GBM) and create new routes for therapy, my lab has been focusing on oncogenic RNA binding proteins (RBPs). RBPs are critical regulators of gene expression and are often altered in cancer. We have identified SERBP1 (Serpine RNA binding protein 1) as a novel oncogenic RBP in GBM. SERBP1 high expression correlates with poor patient prognosis and influences treatment response. We established that SERBP1 regulates critical metabolic routes (One Carbon, Methyl and MTA cycles) and this regulation leads to activation of cell cycle, tumor growth, proliferation of glioma stem cells and silencing of genes implicated in neuronal differentiation. Our study has two major goals. We have determined that by affecting "cancer metabolism" (methionine production in particular), SERBP1 influences epigenetic regulation (gene silencing via histone methylation). We will use genomic methods to expand our initial study, build a SERBP1 regulatory map and define genes and molecular pathways affected by SERBP1 via epigenetic regulation. In the second part of our project, we will conduct a biochemical/structural analysis to characterize SERBP1 RNA binding properties. This information will be used next to devise a high throughput screening (HTS) to identify SERBP1 inhibitors capable of blocking its RNA binding activity. Top hits will be later evaluated into their capacity of blocking SERBP1 function and disrupt cancer phenotypes. Finally, we will identify epigenetic inhibitors synergizing with SERBP1 inhibitors and develop a combined strategy to be used in GBM therapy. We are the first ones to report SERBP1 oncogenic activities in GBM and to show that an RBP can function as a key regulator of metabolic pathways. "Cancer metabolism" and epigenetic regulation are two areas of high interest in cancer therapy. Thanks to its impact on both processes, SERBP1 targeting could provide a unique and robust treatment alternative.

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