Prof. Dr. Felix H. Brembeck
Professor of Tumor Biology and Signal Transduction
- Dr. med., Free University Berlin, 1997
- Postdoctoral Fellow, Harvard Medical School, Boston, USA 1998
- Postdoctoral Fellow, University of Pennsylvania, Philadelphia, USA, 1998-2000
- Senior Postdoctoral Researcher, Max-Delbrueck-Center For Molecular Medicine Berlin, 2000-2008
- Professor of Tumor Biology and Signal Transduction, Department of Hematology and Oncology, Georg-August-Universität Göttingen, since 2008
- Project Leader DFG Forschergruppe FOR942 “Wnt signaling in tumor progression and development” since 2008
Homepage Department/Research Group
Major Research Interests
Main topic of our laboratory is the molecular analysis of epithelial proliferation and differentiation in vitro and in vivo during development and tumorigenesis in humans and mice.
One focus of our current research is the canonical Wnt/beta-catenin signaling pathway and the role of their specific co-factors, BCL9 and Pygopus. We have previously identified BCL9-2 in humans, the homolog of the proto-oncogene product BCL9, which plays a crucial role in the switch between beta-catenin’s adhesive and transcriptional functions. The mammalian BCL9 proteins and Legless, the orthologue of Drosophila, are essential components of the canonical Wnt/beta-catenin signaling pathway. BCL9/Legless proteins establish a nuclear complex with beta-catenin/armadillo and enhance Lef/Tcf/beta-catenin-dependent transcription. A further component, Pygopus, is also part of the nuclear BCL9/beta-catenin complex. Pygopus is also required for Wnt-signaling and modulates chromatin remodeling and histone modifications. Legless and Pygopus are absolutely required for Wnt/ beta-catenin signaling in Drosophila, but we have demonstrated that their role in mammalians is tissue- and context-specific and that BCL9/Pygopus regulate distinct gene signatures.
Our research is dedicated to study the function of BCL9/Pygopus proteins in different types of tissues during development and in disease. We also analyze their role as oncogenes for the initiation and progression of tumors. Moreover, we characterize in depth the mechanisms of gene regulation by the BCL9/Pygopus, in context of the Wnt- and other signaling pathways. For this, we apply a broad variety of molecular biology methods in vitro and in vivo using genetic mouse models, primary tissue cultures, ES cell cultures and established tumor cell lines. We study gene function in biological assays and aim to identify new interacting molecules.
Selected Recent Publications
- F. H. Brembeck*, M. Wiese, N. Zatula, T. Grigoryan, Y. Dai, J. Fritzmann, and W. Birchmeier, BCL9-2 promotes early stages of intestinal tumor progression, (2011) Gastroenterology, 141:1359-1370. (* corresponding author)
- F. Nitzki, A. Zibat, S. Konig, M. Wijgerde, A. Rosenberger, F. H. Brembeck, P. O. Carstens, A. Frommhold, A. Uhmann, S. Klingler, J. Reifenberger, T. Pukrop, F. Aberger, W. Schulz-Schaeffer, and H. Hahn, Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch-mutant mice via CaMKII, (2010) Cancer Res., 70:2739-2748.
- J. Fritzmann, M. Morkel, D. Besser, J. Budczies, F. Kosel, F. H. Brembeck, U. Stein, I. Fichtner, P. M. Schlag, and W. Birchmeier, A colorectal cancer expression profile that includes transforming growth factor beta inhibitor BAMBI predicts metastatic potential, (2009) Gastroenterology, 137:165-175.
- F. H. Brembeck, M. Rosario, and W. Birchmeier, Balancing cell adhesion and Wnt signaling, the key role of beta-catenin, (2006) Curr. Opin. Genet. Dev., 16 51-59.
- U. Stelzl, U. Worm, M. Lalowski, C. Haenig, F. H. Brembeck, H. Goehler, M. Stroedicke, M. Zenkner, A. Schoenherr, S. Koeppen, J. Timm, S. Mintzlaff, C. Abraham, N. Bock, S. Kietzmann, A. Goedde, E. Toksoz, A. Droege, S. Krobitsch, B. Korn, W. Birchmeier, H. Lehrach, and E. E. Wanker, A human protein-protein interaction network: a resource for annotating the proteome, (2005) Cell, 122:957-968.
- F. H. Brembeck, T. Schwarz-Romond, J. Bakkers, S. Wilhelm, M. Hammerschmidt, and W. Birchmeier, Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions, (2004) Genes Dev., 18:2225-2230.
- F. H. Brembeck, F. S. Schreiber, T. B. Deramaudt, L. Craig, B. Rhoades, G. Swain, P. Grippo, D. A. Stoffers, D. G. Silberg, and A. K. Rustgi, The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice, (2003) Cancer Res., 63:2005-2009.
- F. H. Brembeck, J. Moffett, T. C. Wang, and A. K. Rustgi, The keratin 19 promoter is potent for cell-specific targeting of genes in transgenic mice, (2001) Gastroenterology, 120:1720-1728.