Dr. Felix Seyfried

Dr. Felix Seyfried is a physician scientist in the Department of Pediatrics and Adolescent Medicine (Head: Prof. Dr. K.-M. Debatin). His major research interest is to elucidate aberrant activated survival pathways and deficient cell death signaling in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is the most common malignancy in childhood and adolescence.

The dependency of leukemias on altered signaling pathways at diagnosis influences the disease evolution and the outcome of patients. The identification and monitoring of pathway alterations, which contribute to leukemogenesis or determine sensitivity or resistance of ALL cells to (targeted) therapy, will be useful to guide molecular therapeutic approaches. Pro- and anti-apoptotic members of the BCL-2 family proteins are key regulators of the intrinsic apoptosis pathway, therefore serving as potential targets for therapeutic intervention. Using synthetic pro-apoptotic peptides in a flow cytometry-based approach, BH3-profiling, developed by Prof. A. Letai (Dana-Farber Cancer Institute, Harvard Medical School, Boston), he identified a strong association of mitochondrial BCL-2 dependence with leukemia-free survival times after in vivo therapy of ALL patient-derived xenografts with the BCL-2-directed inhibitor venetoclax. However, some leukemias demonstrated resistance to the BCL-2 inhibitor by shifting their BCL-2-dependence to other molecules, such as BCL-XL or MCL-1. Thus, analyzing the functional interplay of mitochondrial apoptosis signaling parameters will enable to select patients who will benefit from treatment with a novel inhibitor. In current projects, dependencies of leukemias on pro-survival signals of apoptosis regulators are addressed at the functional level. The main goals of the research are to evaluate the efficacy of directed therapies in ALL, to identify mechanisms determining sensitivity or resistance and to establish strategies to predict treatment response of patients to targeted treatment prior to therapy.