Area of research
Our group has a long-standing interest in mast cells and mast cell-related diseases including mastocytosis, anaphylaxis, angioedema and atopic dermatitis. Mastocytosis is a heterogenous disease characterized by clonal expansion of mast cells in multiple organs, particularly the bone marrow and skin. Clinical manifestation includes mast cell mediator symptoms such as anaphylaxis as well as dysfunction of various organ systems such as cytopenia, hepatosplenomegaly, and malabsorption. The most common molecular alteration is an activating mutation in the KIT gene, KITD816V, carried by more than 90% of patients. Additional oncogenic mutations are typically found in patients with advanced disease categories like mast cell leukemia, most commonly in the genes TET2, SRSF2, ASXL1 and JAK2. The course of the disease ranges from chronic in non-advanced categories to progressive in advanced categories. Current treatment options include antihistamines, omalizumab, and new KIT-targeting tyrosine kinase inhibitors (TKI) like midostaurin and avapritinib, but are often not sufficient to control symptoms.
At the University Hospital Basel we see mastocytosis patients from all over Switzerland in the Interdisciplinary Mastocytosis Clinic. The Mastocytosis Clinic is one of the few centres worldwide that participates in clinical trials investigating several new compounds such as the KIT-targeting TKIs avapritinib, elenestinib and bezuclastinib. We are currently establishing and maintaining a clinical database and a biobank of patients with mastocytosis. Furthermore, patients seen in the Mastocytosis Clinic are enrolled in the international patient registry of the European Competence Network on Mastocytosis (ECNM) after informed consent.
During the past years, we were able to identify novel biomarkers and therapeutic targets, we detected new KIT mutations in familial mastocytosis, developed new classifications and diagnostic criteria and initiated and conducted clinical trials in mastocytosis. We also generated novel Cre-transgenic mouse models with conditional expression of KIT for research on mastocytosis and mast cells.