Group Vassella

microRNAs are short regulatory RNAs at the post-transcriptional level that are implicated in a wide variety of basic biological processes as well as in cancer. My research team is aiming at identifying microRNAs that are implicated in resistance to chemo- and targeted therapy of non-small cell lung cancer and gliomas. Our results suggest that antagomirs that block the expression of endogenous microRNAs could be used in adjuvant cancer therapy.

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 brain tumours of childhood, molecularly defined by different groups and subtypes. Though medulloblastoma is a rare disease, it has been also described in post-pubertal and adult patients. However, due to lack of studies exclusively on adult medulloblastomas, the therapeutic approach of these patients mostly relies on pre-existing data from studies focused on medulloblastomas of the paediatric population. On these grounds, and considering that adult patients do not present a satisfying clinical outcome post-therapy, we aim to investigate 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 the development of a molecular risk-adjusted targeted therapy.   

Overview of the molecular subgroups and subtypes of pediatric medulloblastoma (Cavalli FMG, et al. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. Jun 12 2017)