Cancer Autophagy Group

My research team investigates molecular mechanisms involved in the pathogenesis of acute myeloid leukemias (AML). Currently, we are deciphering the function of autophagy and the transcription factor PU.1 in this disease. Additional research projects led by Magali Humbert (AML) and Anna Schläfli (Breast cancer) address the function of the autophagy recycling pathway in the resistance of hematological and solid cancers to chemotherapeutic agents and targeted therapies. All these pre-clinical studies in targeted, personalized cancer therapy are conducted in close collaboration with clinical pathologists and the Translational Research Unit.

Current research projects

Function of Chaperone-Mediated Autophagy in Myeloid Leukemia Therapy

Group Tschan While classification of the heterogeneous blood cancer, acute myeloid leukemia (AML) improved significantly, scarce progress has been made in terms of treatment. Relapse and therapy failures remain high due to chemotherapy-resistant leukemic cells (CRLC). Our preliminary data link increased chaperone-mediated autophagy (CMA) to resistance mechanisms in differentiation therapy and an immature developmental stage of AML blasts. Therefore, we are aiming at understanding the role of CMA in the biology of AML cells and CRLC including the interaction with the microenvironment.




Chaperone mediated autophagy (CMA) (A) CMA signaling pathway. (B) LAMP2A and HSC70 co-localization in NB4 AML cells

Understanding the role of autophagy in retinoic acid therapy of breast cancer

Group Tschan Epithelial-to-mesenchymal transition (EMT) plays a key role in therapy-resistance and metastasis formation. In the present study, we therefore aim at reversing the EMT phenotype of breast cancer cells using differentiation-based therapy based on all-trans retinoic acid (ATRA). Cellular differentiation is often associated with upregulation of autophagy. Autophagy is a lysosomal degradation and recycling system and may supports cellular differentiation by removing superfluous organelles, keeping energy levels or by regulating signaling by selective removal of proteins. Therefore, we study autophagy functions during therapy-induced MET and how modulation of autophagy can support differentiation-based therapy. Furthermore, we investigate how cancer associated fibroblasts influence cancer autophagy and therapy efficiency.


Cancer-associated fibroblasts co-cultured with SKBR3 breast cancer cells (green). Staining: autophagy marker LC3B (red)

Identification and analysis of PU.1 cell death pathways

Group Tschan The ETS-transcription factor PU.1 is needed throughout hematopoietic differentiation particularly by orchestrating terminal differentiation of macrophages and neutrophils. Importantly, low PU.1 expression can lead to the transformation of myeloid progenitor cells to acute myeloid leukemia (AML) blast cells. We found a new tumor suppressor function for PU.1 by supporting TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in AML cells. Currently, we are investigating how PU.1 regulates alternative splicing of anti-apoptotic genes and how this affects AML therapy responses.



PU.1 in TRAIL-induced apoptosis (A) PU.1 represses NF-κB. (B) PU.1 affects expression or alternative splicing of anti-apoptotic genes



Oslo, February, 2018
Sarah Parejo: In this short-term scientific mission, I had the opportunity to visit Norway and to learn how to perform the LDH sequestration assay in the laboratory of Dr. Nikolai Engedal at the Centre of Molecular Medicine in Oslo. Furthermore, we carried out experiments to advance our project on ALK-inhibition in EML4-ALK positive lung cancer cells. The results we obtained demonstrate that targeting ALK with Ceritinib stimulates autophagic activity in our model, suggesting a potential role of autophagy in drug resistance to ALK targeted therapies in lung cancer. My six week stay in Oslo was truly an exciting and instructive experience. I was able to benefit from the great expertise of Nikolai Engedal and his lab members, and we will implement the LDH assay in our laboratory in Bern.