Group Vassella

Gliomas and medulloblastomas are the most common aggressive brain tumours in adults and children, most of which are associated with a fatal prognosis. The focus of our research group includes the molecular characterisation of glioblastomas and adult medulloblastomas with the aim of further defining the molecular profile of these tumours for the development of targeted therapy. To this end, we perform whole exome sequencing, genome-wide methylation and transcriptome analyses as well as microRNA and CRISPR/CAS9 library screens.

Current research projects

Role of serine-threonine phosphatases in temozolomide resistance of glioblastoma

Group Vassella We followed an unbiased approach for the identification of microRNAs that are most efficient at conferring resistance to the alkylating agent temozolomide in glioblastoma cells, which are the most common and most aggressive primary malignant brain tumour.  To this end, glioblastoma cell lines were screened with a lentiviral microRNA library and selected for temozolomide resistance. miRNAs identified by this screen showed downregulation of serine-threonine phosphatases, which in turn caused enhanced phosphorylaton of ERK and AKT, modulated the activity of DNA repair enzymes, and thereby confer resistance to TMZ response. 


Screening for microRNAs conferring temozolomide resistance in glioblastoma cell lines

Molecular characterization of recurrent glioblastoma

Group Vassella Glioblastoma (GBM) is the most heterogeneous and aggressive primary brain tumors, and represents a particular challenge of therapeutic intervention. In a single-center retrospective study of 43 matched initial and post-therapeutic GBM cases with exceptionally long recurrence period, we performed whole exome sequencing in combination with mRNA and microRNA expression profiling with the aim to identify processes altered in recurrent GBM. Seven mRNAs coding for proteins implicated in Epithelial to Mesenchymal Transition (EMT) and 13 miRNAs implicated in Tumor Necrosis Factor (TNF) and Wnt signaling pathways were significantly dysregulated. To the best of our knowledge, this is the largest cohort of recurrent GBM with long-term resection intervals, that has been analyzed by multi-omics approaches In future, this approach may help for the development of new personalized medicine. This project is currently supported by the Swiss National Science Foundation.

Heat map analysis of recurrent glioblastoma

Clinical, pathological and molecular characterization of adult medulloblastomas for targeted therapy: a multicenter cohort study including primary and relapse cases

Group Vassella Medulloblastomas are the most common aggressive pediatric brain tumors, molecularly defined by different groups and subgroups. Although medulloblastoma is a rare disease, it has been also described in postpubertal and adult patients. The lack of studies exclusively on adult medulloblastomas means that the therapeutic approach in these patients is mainly based on existing data from studies on pediatric medulloblastomas. For these reasons, and given that adult patients do not have a satisfactory clinical outcome after therapy, we would like to study a large cohort of adult medulloblastomas and medulloblastoma relapses on a clinical, pathological and molecular level in order to further characterize the biology of these tumors for developing a targeted therapy adapted to their molecular profile.

Classic histomorphology of an adult medulloblastoma