Epic-ZENITH: An integrative effort to identify regulators of metabolism and epigenetics in the context of glioblastoma-associated myeloid cells – Epic-ZeNITH

A distinctive feature of cancer and the anti-tumour immune response is metabolic reprogramming. There is a link between metabolic and epigenetic changes but the mechanisms involved are unknown due to technical limitations. Currently, there are no methods to study concomitantly metabolism and epigenetics in tumour-derived cells of patients. An ideal cell type to study metabolism and epigenetics are monocyte derived myeloid cells, because they are sensitive to their environment and can differentiate into efferocytic, angiogenic or inflammatory. Glioblastoma tumors are ideal to study metabolism and epigenetics because it is characterized by three different microenvironments that are infiltrated by monocytes; the necrotic region, the angiogenic region and the edematized or infiltrative region. My objectives are 1) to create a complete metabolic map of the three characteristic regions of glioblastoma (GBM); 2) to identify the metabolic profile, transcriptomic and epigenetic signatures of the myeloid cells associated with the three GBM regions using an original method; 3) to identify the signaling pathways that regulate metabolism, identify markers and validate them in a retrospective GBM cohort. This integrative project aims to combine standard of care imaging in-vivo, with ex-vivo deep analysis to identify the metabolites, enzymes, transcription factors and regulatory genetic elements that can be used as targets in myeloid cells to modulate their function in the context of glioblastoma.