Integrative multi-omics analysis of IDH mutant gliomas to reveal novel targets for treatment

Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define glioma subtypes and are primary events in gliomagenesis, impacting tumor epigenetics and metabolism. We have recently identified a novel metabolic vulnerability in the glutathione synthesis pathway that may be therapeutically exploited. Here we expand these studies leveraging integrated multi-omics data of patient samples including genetic/epigenetic, transcriptomic, metabolomic and proteomic data to reveal other metabolic deficiencies in IDH wildtype and IDH mutant gliomas. Our preliminary data indicate that rewiring of the butyrate pathway could reveal a novel metabo-epigenetic regulation, associated with an alteration in the gut-brain axis crosstalk in glioma. We will apply epigenetic drugs on CRISPR-engineered glioma models to test their impact on metabolic and epigenetic regulations and glioma features.