Plexins comprise a family of transmembrane receptors for semaphorins, which are centrally involved in cell-cell communication and regulate key cellular functions. The semaphorin-plexin system plays a pivotal role in various developmental processes such as axon guidance, synapse assembly, angiogenesis, or cardiac and renal development. Work of the last decade has also revealed critical functions of the semaphorin-plexin system in the physiology and pathophysiology of the adult organism, particularly in the immune and bone system as well as in cancer. Thus, semaphorins and plexins represent novel pharmacological targets for drugs to prevent or treat various diseases.
By combining biochemical methods, siRNA screens, proteomics, three-dimensional cell culture models, in vivo mouse transgenics and mouse models of disease, we aim at the identification of critical determinants of plexin signaling and at the elucidation of their relevance for biological processes. Major scientific goals of the lab comprise the characterization of the roles of semaphorins and plexins in tumor growth, invasion and metastasis, in epithelial morphogenesis, homeostasis and repair, as well as in inflammation and metabolism. In a translational approach, we are exploiting our data on the cellular signal transduction and pathophysiological functions of plexins to develop therapeutic pharmacological agents that target the semaphorin-plexin system. Along this line, we raise antibodies against particular plexins which block the binding of semaphorins or modulate plexin signal transduction. In addition, we design assay systems, which allow for the identification of small molecules that specifically interfere with the interaction between particular semaphorins and their respective plexin receptors. These agents are then tested preclinically in vitro and in mouse models of diseases such as cancer, multiple sclerosis and osteoporosis.
Javier Fernández Baldovinos
phone +49 (0)6421 28-65111 email: Javier Fernández Baldovinos
phone +49(0)6421 28-65111 email: Jiang Chen
phone +49(0)6421 28-65111 email: Carsten Höß
phone +49(0)6421 28-65111 email: Florian Hub
phone +49 (0)6421 28-65111 email: Ivana Matkovic
phone +49 (0)6421 28-65005 email: Thomas Worzfeld
phone +49 (0)6032 705-1269 email: Rui Xu
phone +49(0)6421 28-65111 email: Susanne Ziegler-Hänel
Xia, J., Swiercz, J.M., Bañón-Rodríguez, I., Matković, I., Federico, G., Sun, T., Franz, T., Brakebusch, C.H., Kumanogoh, A., Friedel, R.H., Martín-Belmonte, F., Gröne, H.J., Offermanns, S., Worzfeld, T. (2015)
Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair.
Dev. Cell. 33:299-313
Worzfeld, T. and Offermanns, S. (2014)
Semaphorins and plexins as therapeutic targets
Nat. Rev. Drug Discov. 13:603-621
Worzfeld, T., Swiercz, J.M., Sentürk, A., Genz, B., Korostylev, A., Deng, S., Xia, J., Hoshino, M., Epstein, J.A., Chan, A.M., Vollmar, B., Acker-Palmer, A., Kuner, R. and Offermanns, S. (2014)
Genetic dissection of plexin signalling in vivo.
Proc. Natl. Acad. Sci. USA 111:2194-2199
Worzfeld, T., Swiercz, J.M., Looso, M., Straub, B.K., Sivaraj, K.K. and Offermanns, S. (2012)
ErbB-2 signals through Plexin-B1 to promote breast cancer metastasis.
J. Clin. Invest. 122:1296-1305
Zielonka, M., Xia, J., Friedel, R.H., Offermanns, S. and Worzfeld, T. (2010)
A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system.
Exp. Cell. Res. 16:2477-2486
Worzfeld, T., Rauch, P., Karram, K., Trotter, J., Kuner, R. and Offermanns, S. (2009)
Mice lacking Plexin-B3 display normal CNS morphology and behaviour.
Mol. Cell. Neurosci. 42:372-381
Korostylev, A.*, Worzfeld, T.*, Deng, S., Friedel, R.H., Swiercz, J.M., Vodrazka, P., Maier, V., Hirschberg, A., Ohoka, Y., Inagaki, S., Offermanns, S. and Kuner, R. (2008)
A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis.
Development 135:3333-3343 * Joint first authors