Bernasconi Furtwängler group  Prof. Dr. Michele Bernasconi

We aim to improve existing therapies for pediatric solid tumors and to develop more effective and less toxic treatment strategies, with a particular focus on rhabdomyosarcoma and Wilms tumor. 

Pediatric sarcomas account for approximately 15% of childhood cancers, and relapse rates remain high with an extremely poor prognosis. Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Two major prognostic subgroups are recognized: fusion-negative (FN) RMS, present in about 55% of patients and associated with a five-year event-free survival of ~70%, and fusion-positive (FP) RMS, present in ~20% of patients with a markedly lower five-year event-free survival of ~23%. Wilms tumor (WT), or nephroblastoma, is the most frequent renal tumor in childhood. While curative therapy is achievable in the majority of cases, patients with high-risk tumors (blastemal or anaplastic histology) have significantly poorer survival. Moreover, current treatment regimens are associated with relevant long-term sequelae, including secondary neoplasms, cardiac insufficiency, infertility, and renal impairment. 

CAR T cells are genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs). CAR T-cell therapy represents one of the most promising approaches for relapsed or otherwise refractory cancers. 

Since 2018, our laboratory has focused on advancing this personalized immunotherapy by strengthening the patient’s immune capacity to recognize and attack tumors. Using proteomics, we investigate the surfaceome to identify novel targets for CAR T-cell therapy. We then perform in vitro and in vivo studies to enhance CAR T-cell activity and therapeutic efficacy.

Medová Group PD Dr. med. Michaela Medová

Tyrosine kinase receptors activate a wide range of different cellular signaling pathways. Physiologically, intact signaling via the MET receptor is indispensable in embryonic development and tissue homeostasis. At the same time, MET dysregulation promotes features clearly associated with tumor growth and progression such as uncontrolled proliferation, angiogenesis, local invasion, and systemic dissemination. 

Accumulating data suggest that MET signaling may also protect tumor cells from DNA damage, hence relating its aberrant activity to resistance to DNA-damaging agents routinely used in cancer treatment. 

We have identified a previously unreported phosphorylation site on MET, which can be recognized by DNA damage master kinases and is involved not only in cellular responses towards DNA damage, but also in metastatic processes, cancer cell migration, and anchorage-independent growth. 

This project aims at dissecting the nature, function, and regulation of this phosphorylation site in oncogenic signaling of the receptor.

Peng group  Prof. Ren-Wang Peng

Lung cancer and malignant pleural mesothelioma (MPM) are major thoracic tumors characterized by high morbidity and mortality, as well as high heterogeneity and resistance to therapy. 

There is an unmet need for a better understanding of the resistance mechanisms, the identification of novel targets and strategies to prevent or overcome therapeutic resistance, and the rational development of precision medicine approaches for personalized disease management to improve clinical outcomes for patients with thoracic tumors.