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
Dr. Lutz Zwillenberg-Prize 2018 On the occasion of the 184th Dies Academicus of the University of Bern the Dr. Lutz Zwillenberg Prize for an outstanding publication or PhD thesis in Biological Sciences was awarded to Dr. Ulrich Baumgartner, for his dissertation "microRNAs as modulators of cell-signaling and their role in chemoresistance in solid cancer". His findings show that a large number of microRNAs (short RNA molecules, which play a key role in gene regulation) orchestrate the activity of oncogenic processes and thereby promote the progression of non-small cell lung cancer. These basic findings in tumor biology might lead to the development of new targeted therapies.
PhD Thesis Elham Kashani successfully defended her PhD Thesis on 17.08.2022. Titel: «Novel therapy resistance mechanisms in Gliomas; a translational and functional investigation»
