Lene Uhrbom – A cell of origin-based strategy to decipher glioma biology

My research is focused on understanding how various glioma-relevant genetic alterations affect tumour development, progression and response to treatment depending on which cell type the tumour originated from. The goal is to uncover glioma-specific mechanisms to which directed therapies will be tested in our pre-clinical models.

Glioma is a large and heterogeneous group of primary CNS tumours comprising astrocytoma, oligodendroglioma and ependymoma of different malignancy grades (I-IV). Glioma can strike at any age but the majority of patients are older adults. Only grade I tumours are benign while grade II-IV tumours are malignant. Glioblastoma is a grade IV glioma and the most common form of all primary malignant brain tumours with dismal prognosis and essentially no cure. In my group we study different types of malignant glioma with a particular interest in glioblastoma.

Recent large-scale efforts to uncover the genetic and epigenetic landscape of glioma has led to a comprehensive molecular characterization of this disease revealing a vast inter- and intratumour heterogeneity. Although biologically informative the molecular classification has not led to a breakthrough in the clinical management of malignant glioma.

The role of the cell of origin

The cell of origin for glioma, including glioblastoma, is generally presumed to be a neural stem cell or glial progenitor cell but this has not been formally proven. For a complete understanding of glioma biology, we think that it is essential to understand how the cell of origin affects the phenotype of cancer cells. My research is centred on investigating this with focus on tumour development, progression and response to treatment.

Our studies are mainly carried out using life-like glioma mouse models and our continuously growing biobank of human glioma cell cultures (HGCC) established from patient surgical samples. By integrating in vitro and in vivo studies and using cross-species bioinformatics we have recently uncovered a list of candidate genes that could be involved in shaping the malignancy and drug response phenotype of glioblastoma cells of different origin.

Through further investigations of these genes and of other aspects of the glioblastoma cell of origin we hope to reveal new mechanisms, pathways and targets that could move us closer to a cure for this disease.
 

Projects

  • Maintenance and expansion of the HGCC biobank.
     
  • Cell of origin for glioblastoma as a basis for stratification, target identification and drug screening.
     
  • The interplay between cell of origin, oncogenic activation and developmental age in glioma development.
     
  • Role of LGR5 in glioma stem cells.
     
  • Investigations of human glioblastoma cell cultures of the mesenchymal subtype.