Understanding the microenvironmental landscape of brain malignancies, and exploring novel candidate genes

Brain tumors can be viewed as “wounds that can’t stop the healing process”, and therefore, comparison between neuro-inflammation and cancer may suggest how the normally immune-suppressive microenvironment of the brain shifts towards a tumor-supporting phenotype.

We explore factors that regulate neuroinflammation and the interplay between tissue resident cells and immune cells in glioblastoma (GBM), focusing on the alarmin IL-33, which has emerged as an important regulator in tissue damage.In addition, GBM can sculpt the brain-specific extracellular matrix (ECM) to support tumor progression.

Proteoglycans, e.g. heparan sulfate (HS) are important components of the brain ECM and we have shown that HS remodeling is part of the malignant brain tumor signature. We now aim to establish the efficacy of inhibiting degradation of HS as a possible treatment.

This is novel because few drug targets have been directed at molecules in the brain tumor microenvironment.Our second aim is to find new candidate genes for GBM.

Frequent GBM somatic mutations have been described but most studies focused on the 1-2% of the genome that codes for protein.

Here we aim to decipher non-coding regulatory regions, stratifying functional variants from passenger mutations among the huge number of non-coding mutations.

Emerging results are expected to validate and suggest new clinically actionable targets across our well-characterized cohort of GBM patients.