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

Three photos showing cultured human glioma cells
   Primary glioma cells cultured
   from a human biopsy.
                 Photo: Uhrbom lab

Glioblastoma is the most frequent and aggressive primary malignant brain tumour with an urgent need for new therapies. My research is focused on investigating different aspects of glioblastoma biology with the goal to identify common mechanisms in subsets of tumours. The knowledge will provide a basis for developing targeted therapies that will be tested in our patient-derived pre-clinical models.

Glioblastoma is the most frequent primary malignant brain tumour. It can occur at any age but the majority of patients are older adults. Median survival is despite aggressive treatment only 15 months and the 2-year survival is 17%, which makes it one of the most severe cancers. Most patients are affected by fatal recurrences which are largely being attributed to the highly invasive, heterogeneous and plastic nature of glioblastoma cells.

My research is focused on molecular and functional investigations of glioblastoma. The overarching goal is to reveal new knowledge of glioblastoma biology that can be used to develop more efficient therapies. We believe that it is important to identify, not only molecularly but also functionally distinct subgroups of glioblastoma, and understand their unique driver mechanisms. This could uncover pathways and targets that we can test in our pre-clinical models.

A biobank with stem cell cultures from glioblastoma

We put large efforts into working with models that are derived from on patient samples and are relevant for and cover the large differences between and within glioblastoma tumours. We have previously established the biobank HGCC (Human Glioblastoma Cell Culture, hgcc.se). It holds over 150 glioblastoma stem cell cultures, a collection of unique serum-cultured glioblastoma stem cells and a glioblastoma tissue microarray.

We are currently collecting a new set of patient samples where we receive several biopsies of different parts of the tumour from each patient, both from the invasive tumour front and the tumour core. The samples are used for primary cell culture, orthotopic xenografts and molecular analyses. This will provide an important complement to the HGCC biobank and will be very valuable in our projects to find new and clinically relevant information about glioblastoma.

Projects

  • Epigenetic and developmental regulation of glioblastoma stem cells (collaboration with Xingqi Chen, Uppsala University)
     
  • Stages and transitions of glioblastoma development from a defined glial cell of origin (collaboration with Goncalo Castelo-Branco, Karolinska Institutet)
     
  • Function and signalling of LGR5 in glioblastoma stem cells
     
  • Tumour cell heterogeneity in IDH1 mutant primary glioblastoma
     
  • Biology of the invasive and relapse-prone glioblastoma cells