Institute of Biology III
PhD student with Junior Fellow Katja Arndt
Sven Hagen received his degree in Biology at the beginning of 2007 from the Georg-August University Göttingen, Germany. His Diploma thesis, which was carried out at the University Clinic of Göttingen under the supervision of Prof. Dr. Dr. med. R. Steinfeld, focused on the interaction of proteins that are causative associated with neurodegenerative disorders in children. In January 2009, Sven Hagen joined the Freiburg Institute for Advanced Studies (FRIAS) at the Albert-Ludwigs University Freiburg as a PhD student in the research group of Dr. Katja Arndt.
The group of Katja Arndt works on the development and application of interfering peptides (iPEP) specifically directed against protein-protein interaction domains of transcription factors such as Jun, Fos, Myc and AF10. Peptides are developed using a semi-rational approach with different in vitro and in vivo selection systems. In this context, Sven Hagen will concentrate on targeting the leukemogenic fusion protein MLL-AF10 and CALM-AF10. Non-random chromosomal translocation results in these fusion proteins comprising the coiled-coil domain of the transcription factor AF10 and the proteins MLL or CALM and subsequently causes certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma, and the H3K79 methyltransferase hDOT1L. The lab successfully enriched peptides that bind the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type interaction partner. This work dissects molecular determinants mediating coiled coil associated AF10 interaction and comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Our aim is to recognize and block the leukemia-associated AF10 interaction, which may have significant implications in future diagnostics and therapeutics.