Research Background

Gliomas are a type of brain tumor that originates in the glial cells, which are supportive cells that surround and nourish nerve cells in the brain. These tumors can occur in various parts of the brain and spinal cord. Gliomas are classified based on the type of glial cell they affect, with common types including astrocytomas, oligodendrogliomas, and ependymomas.

Gliomas are graded on a scale from I to IV based on their aggressiveness, with higher grades indicating more malignant tumors. Grade I and II gliomas are considered low-grade and tend to grow slowly, while Grade III and IV gliomas are high-grade and more aggressive. Diagnosis typically involves imaging studies such as MRI or CT scans, and a definitive diagnosis often requires a biopsy. Treatment for gliomas depends on factors such as the tumor type, grade, and location. Common approaches include surgery, radiation therapy, and chemotherapy.

Prognosis for glioma patients varies widely and is influenced by factors such as tumor grade, location, and the individual’s overall health. While some gliomas are more treatable and associated with better outcomes, high-grade gliomas, particularly glioblastoma multiforme (GBM), are challenging to treat and have a poorer prognosis. Ongoing research aims to improve the understanding of gliomas and develop more effective treatment strategies. GBM exhibits resistance to treatment and carries a grim prognosis owing to its consistently recurring nature. The recurrence is attributed to its rapid growth and invasion into the surrounding normal brain tissue, typically manifesting within a 12-month period. Among brain tumors, high-grade glioma (HGG) stands out as the most prevalent and malignant. Notably, HGGs display a high degree of heterogeneity.

Our research focuses on high-grade gliomas (HGG), the most aggressive and prevalent brain tumors with limited treatment options and a median survival of 15-18 months post-diagnosis. Previous studies underscore the importance of tumor mesenchymal transformation in glioma malignancy and invasion, presenting a promising target for translational development against HGG. However, a comprehensive understanding of the tumor microenvironment (TME) and its cellular and non-cellular extracellular matrix components in glioma growth, invasion, and therapeutic efficacy is lacking.

Research Projects

The long-term goal is to identify novel targets to provide original therapeutic approaches to inhibit GBM growth and invasion. Our lab research is based on cellular cancer biology studies, including in-vitro, ex-vivo patient-derived, and in-vivo pre-clinical murine glioma models, with the main goal of focusing on projects that have high potential for immediate clinical translation.

Dr. Comba research comprises three interconnected projects in the field of Neuro-oncology. These projects aim to elucidate:

1) The role of the tumor extracellular matrix (ECM) in glioma growth and invasion, where we investigate the molecular landscape of cells controlling ECM production and remodeling.

We aim to identify:

i) Mutually exclusive molecular biomarkers at the transcriptomic and proteomic levels of the mesenchymal cell population.

ii) Longitudinal evaluation after recurrence.

iii) Relationship to glioma malignancy. 

Experimental approaches:

Spatial Transcriptomics Analysis:

Functional Evaluation of Genetic Targets:

2) Molecular mechanisms of tumor microenvironment heterogeneity and plasticity, aiming to understand the crosstalk between glioma cells and various TME components, including stromal, vascular, and immune cells.

Tumor Microenvironment Plasticity:

Experimental approaches:

Co-culture of tumoral and stromal cells

Mouse Glioma Models

Flow Cytometry Analyses

Spatial Transcriptomics Analyses

Time-Laps Confocal Microscopy Studies

3) Advancing precision oncology by exploring 3D glioma models to unravel antitumoral therapeutic approaches. We develop and optimize innovative integrative analyses to evaluate the impact of genetic targeting combined with other therapies on glioma growth and invasion.

Mouse glioma 3D explant-slices model

Patient-derived glioma 3D explant-slices model

Experimental approaches: