Long-range gene regulation and 3D chromatin organization in glioblastoma
Glioblastoma is the most lethal and aggressive, but also the most common, of all primary brain tumors. Most genetic variants that predispose to cancer are located in non-coding regions enriched in putative enhancers, whose systematic rearrangements have a high impact on gene expression in cancer. Despite the number of susceptibility loci identified in glioblastoma, a functional understanding of how the non-coding regulatory genome contributes to the pathogenesis is missing.
We are interested in how the reprogramming of regulatory regions and topological changes in 3D chromatin organization determine gene dysregulation in glioblastoma, and how this subsequently contributes to malignancy, heterogeneity and invasiveness. To this end, we bring knowledge from different biological and technical backgrounds into the glioblastoma field, employing next generation sequencing approaches, genome editing and live-cell imaging in both glioblastoma mouse models and human glioma cell lines.
Our research aims to shed light on how the interplay between the regulatory and topological architecture of the genome contributes to malignancy and how it integrates cues from the neurons in the tumor microenvironment to orchestrate gene expression in glioblastoma.