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Division of Signal Transduction and Growth Control

Prof. Dr. Peter Angel

The Division is working on the characterisation of the genetic response of organisms and their cells on external signals (growth factors, inflammation-related cytokines, carcinogens and tumor promoters) employing newly generated genetically modified mouse models (which recapitulate features of human diseases) and cell- and organ cultures derived thereof. We want to define and characterize altered gene functions, which result in imbalanced signaling pathways and downstream genetic programs forming the basis for acquired capabilities of uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis and finally enhanced tissue invasion and metastasis. During the past years and presently, we have applied genetically modified animal models, in vitro organ systems, and genome-wide expression analyses in order to decipher the individual functions of AP-1 subunits. Our study of individual AP-1 subunits, of their regulation as well as the identification of distinct targets genes and genetic programs critically involved in cancer development has yielded major contributions to our current understanding of genetic programs in physiological (e.g. embryogenesis, vascular biology/angiogenesis, wound healing) and pathological processes (chronic inflammation, tumorigenesis). In collaboration with clinical partners these studies, accompanied by analyses of human tumor samples have the final goal to define novel molecular markers for diagnosis and therapeutic intervention.

With the goal to bridge basic science and translational research, in collaboration with partners at the DKFZ, University Heidelberg and external partners our Program will focus on intra- and intercellular signaling pathways and downstream genetic programs in cancer to develop and evaluate molecules as potential biomarkers or drug targets. We will utilize state-of-the-art methods including elaborate transgenic mice, various tumor models, interspecies heterologous co-culture cell systems, genome-wide expression and epigenetic analyses combined with systems biological approaches, and molecular and cellular biology to study tumor-relevant genetic networks. We will focus on mechanisms of cell-cell communication in wound healing, and cross-talk between tumor cells and cells of the microenvironment (endothelial-, mesenchymal- and immune cells). Main attention will be drawn on (soluble) mediators of cell communication as well as downstream signalling pathways and genetic programs initiated in the corresponding target cells. The main projects concern:
1. Physiology and pathology of wound healing: controlling genetic programs of cell proliferation, migration and differentiation
2. function of the cell surface protein podoplanin in brain and skin tumors
3. genetic and epigentic programs of tumor angiogenesis; role of the tumor stroma
4. function of the cell surface receptor RAGE and its ligands (S100 proteins) in the regulation of genetic programs in inflammation and cancer

Selected Publications

Szabowski, A., Maas-Szabowski, N., Andrecht, S., Kolbus, A., Schorpp-Kistner, M., Fusenig, N.E. & Angel, P. (2000) c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell 103, 745-755

Hess, J., Angel, P. & Schorpp-Kistner, M. (2004) Functions of AP-1 subunits: Quarrel and Harmony among Siblings. J. Cell Sci 117, 5965-73

Gebhardt, C., A. Riehl, M. Durchdewald, J. Németh, G. Fürstenberger, K. Müller-Decker, A. Enk, B. Arnold, A. Bierhaus, P.P. Nawroth, J. Hess & P. Angel (2008) RAGE signaling sustaines inflammation and promotes tumor development; J Exp Med 205, 275-85

Licht, A.H, Nübel, T., Feldner, A., Jurisch-Yaksi, N., Marcello M., Demicheva, E., Hu, J.-H., Augustin, H.G., Hecker, M., Angel, P., Korff, T., & Schorpp-Kistner, M. (2010) Junb regulates arterial contractility and cellular migration via its direct target Myl9, J Clin Invest 120, 2307-18

last update: 11/11/2011 back to top