Experimental Research Programmes
Head Prof. Dr. med. Thomas Pabst
The molecular pathology of acute and chronic leukemia is being investigated using both cell line models as well as clinical material from patients. Experimental research in the lab is centered on the investigation of the molecular mechanisms underlying the leukemic onset, in particular in acute myeloid leukemia (AML). A hallmark of AML is the accumulation of myeloid precursor cells in the bone marrow. Characteristically, the malignant leukemic cells display a block in their normal differentiation process at particular stages. Research on the pathogenesis of AML is focused on the analysis of oncogenes and tumor suppressor genes which deregulate proliferation and cell death in AML cells. Although the ultimate relationship between altered proliferation and differentiation in AML remains to be elucidated, our current concept indicates that deregulation of the tumor suppressor p53 and the transcription factor CEBPA critically affects both differentiation and apoptosis in AML cells. Novel p53 inducing agents are promising compounds for a targeted AML treatment and we are testing various targeted compounds in preclinical studies and have initiated clinical studies.
A specific focus of our research has been set on AML subtypes characterized by mutations of the myeloid key transcription factor CEBPA. We have investigated both somatic and germline CEBPA mutations leading to sporadic and familial forms of AML. Although familial AML is a rare finding outside of a genetic syndrome, germline mutations appear to be present in up to 10% of AML patients with CEBPA mutations.
Mutations in a second key transcription factor GATA2 can cause myelodysplastic syndromes and AML. Here we are supporting the University Children Hospital Zurich to investigate familial forms of GATA2 deficiencies.
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Cancer Autophagy Group
Our independent research groups (longstanding collaboration with Prof. Mario Tschan, Institut of Pathology, University of Bern) are interested in the pathogenesis of acute myeloid leukemia and malignant lymphomas. We share the interest on the possible role of autophagy in the pathology of these diseases. The discovery of possibly new therapeutic targets, particularly in a highly complex process such as autophagy, fully depends on the knowledge of any process in normal counterpart cells. Whether the autophagy recycling pathway is involved in the resistance of hematological and solid cancers against chemotherapeutic agents and targeted therapies is being analyzed in close collaboration with clinical pathologists.
Is autophagy a rational target in malignant lymphomas?
Malignant lymphomas comprise a variety of diseases. Multiple relapses with the need for new therapeutic targets are a fact. We therefore analyze the role of autophagy in lymphomas and their normal counterpart cells.
Molecular characterization of mediastinal lymphomas in siblings
Although rare, familial clustering of malignant lymphoma is a unique opportunity to unravel the pathogenesis of diseases. We have analyzed a family with two siblings affected with aggressive, mediastinal lymphomas with massively parallel whole-exome sequencing and array CGH.
Non-coding RNAs in lung cancer
Head Dr. med. Simon Haefliger, PhD
Our research group is studying non-coding RNAs in lung cancer with a special focus on microRNAs (miRNAs). MiRNAs are small nucleic acids that contribute to the regulation of gene expression. They are involved in numerous cellular pathways and their expression is dysregulated in human cancer through various mechanisms. We conduct clinical trials and perform translational research studying miRNA and other non-coding RNA expression in lung cancer:
MiRNAs are highly stable in tissue and biofluids such as blood, which makes them attractive as a source for diagnostic, prognostic, and predictive biomarkers. We collect and analyse blood samples of lung cancer patients before and during the course of treatment. Thereby, we aim to identify miRNAs that detect lung cancer at an early stage. Further, we aim to predict and monitor therapy response depending on miRNA expression patterns.
The modulation of miRNA expression in lung cancer could potentially be implemented as a novel therapeutic strategy. We aim to identify and characterize key miRNA networks in order to develop a miRNA-based therapy. Our methods include the analysis of public databases with bioinformatics tools and the modulation of miRNA expression in cancer cells using the CRISPR-Cas9 method.
MiRNAs contribute to the development of resistance mechanisms against established cancer therapies such as chemotherapy and immunotherapy. We study the expression of miRNAs and other non-coding RNAs in resistant lung cancer cells with the aim to understand mechanisms of resistance and the underlying role of non-coding RNA in these processes.
Group Members 9
Group Pabst 3
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Group Novak 3
- Name / Titel
- PD Dr. med. Urban Novak
- Group Leader, Leitender Arzt
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