Lene Uhrbom – Molecular and functional investigations of primary malignant glioma

Our research is focused on different diagnoses of primary malignant glioma for which there is an acute need of new therapies. These brain tumours can occur at any age but are most frequent in older adults. We work with patient-derived glioma models and validated mouse models to uncover biology and regulation with the goal to identify vulnerabilities to which new therapies can be directed.

Primary malignant glioma comprises a large group of diagnoses that can affect both children and adults. Our studies are focused on diffuse gliomas, and in particular the adult tumours glioblastoma IDH wild-type, astrocytoma IDH-mutant and the childhood tumour diffuse pediatric-type high-grade glioma.

Common to these diagnoses is that in spite of extensive treatment with surgery, radiation therapy and chemotherapy there will be treatment-resistant cancer cells remaining in the large majority of patients, which will cause a lethal relapse most often in close proximity to the resection cavity.

Our projects build on two decades of studies, data and publications in the field of brain tumour biology. We work with patient tissues, patient-derived cell cultures and validated mouse models, and use a wide range of functional, phenotypic and molecular analyses to answer questions related to cancer origin, development and therapy resistance.

Biobank with tissues and cell cultures from patients

To increase the likelihood of our results being clinically applicable we are careful to perform our research in models that are biologically relevant and reflect the vast heterogeneity of malignant glioma. To make that possible we have in collaboration with other research groups at the department established a functional biobank, HGCC (Human Glioblastoma Cell Culture), which consists of patient samples and cell cultures from hundreds of patients, of which most are glioblastoma IDH wild-type and the samples taken from the bulk tumour.

My research group is now continuing this work to extend the biobank with more patient samples and cell cultures, focusing on IDH-mutant tumours and samples from the diffusely invasive outer tumour edge.

Projects

  • Cancer cell diversity in IDH-mutant grade 4 astrocytoma
  • Function and signaling of LGR5 in glioblastoma
  • Molecular delineation of diffuse pediatric-type high-grade glioma development from a defined glial cell of origin
  • Biology and targets of the relapse-causing diffusely invasive glioblastoma cells at the outer tumor edge
  • Mechanisms dictating survival in epigenetic glioblastoma subgroups
Image in three parts, one photo of a petri dish with cultivated glioma cells and two microscope images of cultivated glioma cells.

Primary glioma cells cultivated from human biopsy material. Photo: Uhrbom lab.

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