Dr. Kai Schuh
|Office:||+49 (0) 931 31-82740|
|Fax:||+49 (0) 931 31-82741|
Studies in biology and chemistry (Diploma), University of Würzburg, 1987-1994
|PhD, Institute of Pathology, University of Würzburg, 1994-1998|
|Research Fellow, SFB 355/688, 1998-2006|
|Professor of Physiology, University of Würzburg, 2007|
1. Interaction of Ca2+- and NO-dependent Pathways in the Cardiovascular System
(K. Schuh, D. Fetting, T. Fischer, and Co-workers)
Aim of this project is the generation of transgenic mouse models to investigate the interactions of Ca2+- and NO/cGMP-dependent signaling pathways in components of the cardiovascular system. To do so, we combine the tetracycline-regulated Tet-Off system with corresponding transgenes under control of tetracycline responsive elements. As a result, expression of various proteins can be induced tissue-specifically e.g. in vascular smooth muscle cells (SM22α promoter) or in cardiac myocytes (αMHC promoter). Subsequently, the effects of transgenic overexpression on our model systems will be investigated. This project is supported by the IZKF Würzburg.
2. In vivo Relevance of the MAPK pathway inhibitor SPRED
(K. Schuh, M. Ullrich, P. Benz and Co-workers)
Spreds form a new protein family with an N-terminal Enabled/VASP homology 1 domain, a central c-Kit binding domain, and a C-terminal Sprouty-related domain. They are able to inhibit the Ras/ERK signaling pathway after various mitogenic stimulations. In mice, Spred proteins were identified as regulators of bone morphogenesis, hematopoietic processes, allergen-induced airway eosinophilia, and hyperresponsiveness. They inhibit cell motility and metastasis and have a high potential as tumor markers and suppressors of carcinogenesis. First aim of this project is getting a clue about the physiological functions in an entire organism. In order to do so, we used a gene trap model, which results (1) in an ablation of the spred2 gene and (2) in a replacement of the endogenous gene by a reporter gene, allowing the creation of an expression profile of spred2. Furthermore, we are interested in the inhibitory function of Spreds in various tissues and how this is achieved, i.e. which are the interacting partners necessary to exert the inhibitory role. Based on this integrated approach, we hope to gain detailed insights in the molecular mechanisms as well as in the in vivo functions of Spred proteins. This project is supported by the DFG.
Benz, P.M., C. Blume, J. Moebius, C. Oschatz, K. Schuh, A. Sickmann, U. Walter, S.M. Feller, and T. Renne. 2008a. Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. J Cell Biol. 180:205-19.
Oceandy, D., E.J. Cartwright, M. Emerson, S. Prehar, F.M. Baudoin, M. Zi, N. Alatwi, K. Schuh, J.C. Williams, A.L. Armesilla, and L. Neyses. 2007. Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b. Circulation. 115:483-92.
Burkard, N., A.G. Rokita, S.G. Kaufmann, M. Hallhuber, R. Wu, K. Hu, U. Hofmann, A. Bonz, S. Frantz, E.J. Cartwright, L. Neyses, L.S. Maier, S.K. Maier, T. Renne, K. Schuh, and O. Ritter. 2007. Conditional neuronal nitric oxide synthase overexpression impairs myocardial contractility. Circ Res. 100:e32-44.
Bundschu, K., U. Walter, and K. Schuh. 2007. Getting a first clue about SPRED functions. Bioessays. 29:897-907.
Wu, R.X., M. Laser, H. Han, J. Varadarajulu, K. Schuh, M. Hallhuber, K. Hu, G. Ertl, C.R. Hauck, and O. Ritter. 2006. Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. J Mol Med. 84:241-52.
Pula, G., K. Schuh, K. Nakayama, K.I. Nakayama, U. Walter, and A.W. Poole. 2006. PKCdelta regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation. Blood. 108:4035-44.
Kleinschnitz, C., G. Stoll, M. Bendszus, K. Schuh, H.U. Pauer, P. Burfeind, C. Renne, D. Gailani, B. Nieswandt, and T. Renne. 2006. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med. 203:513-8.
Johne, J., C. Blume, P.M. Benz, M. Pozgajova, M. Ullrich, K. Schuh, B. Nieswandt, U. Walter, and T. Renne. 2006. Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma. Biol Chem. 387:173-8.
Hallhuber, M., N. Burkard, R. Wu, M.H. Buch, S. Engelhardt, L. Hein, L. Neyses, K. Schuh, and O. Ritter. 2006. Inhibition of nuclear import of calcineurin prevents myocardial hypertrophy. Circ Res. 99:626-35.
Bundschu, K., U. Walter, and K. Schuh. 2006b. The VASP-Spred-Sprouty domain puzzle. J Biol Chem. 281:36477-81.
Bundschu, K., S. Gattenlohner, K.P. Knobeloch, U. Walter, and K. Schuh. 2006a. Tissue-specific Spred-2 promoter activity characterized by a gene trap approach. Gene Expr Patterns. 6:247-55.
Renne, T., K. Schuh, and W. Muller-Esterl. 2005b. Local bradykinin formation is controlled by glycosaminoglycans. J Immunol. 175:3377-85.
Renne, T., M. Pozgajova, S. Gruner, K. Schuh, H.U. Pauer, P. Burfeind, D. Gailani, and B. Nieswandt. 2005a. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med. 202:271-81.
Cartwright, E.J., K. Schuh, and L. Neyses. 2005. Calcium transport in cardiovascular health and disease--the sarcolemmal calcium pump enters the stage. J Mol Cell Cardiol. 39:403-6.
Burkard, N., J. Becher, C. Heindl, L. Neyses, K. Schuh, and O. Ritter. 2005. Targeted proteolysis sustains calcineurin activation. Circulation. 111:1045-53.
Bundschu, K., K.P. Knobeloch, M. Ullrich, T. Schinke, M. Amling, C.M. Engelhardt, T. Renne, U. Walter, and K. Schuh. 2005. Gene disruption of Spred-2 causes dwarfism. J Biol Chem. 280:28572-80.
Schuh, K., E.J. Cartwright, E. Jankevics, K. Bundschu, J. Liebermann, J.C. Williams, A.L. Armesilla, M. Emerson, D. Oceandy, K.P. Knobeloch, and L. Neyses. 2004. Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility. J Biol Chem. 279:28220-6.
Engelhardt, C.M., K. Bundschu, M. Messerschmitt, T. Renne, U. Walter, M. Reinhard, and K. Schuh. 2004. Expression and subcellular localization of Spred proteins in mouse and human tissues. Histochem Cell Biol. 122:527-38.
Schuh, K., S. Uldrijan, S. Gambaryan, N. Roethlein, and L. Neyses. 2003b. Interaction of the plasma membrane Ca2+ pump 4b/CI with the Ca2+/calmodulin-dependent membrane-associated kinase CASK. J Biol Chem. 278:9778-83.
Schuh, K., T. Quaschning, S. Knauer, K. Hu, S. Kocak, N. Roethlein, and L. Neyses. 2003a. Regulation of vascular tone in animals overexpressing the sarcolemmal calcium pump. J Biol Chem. 278:41246-52.
Ritter, O., K. Schuh, M. Brede, N. Rothlein, N. Burkard, L. Hein, and L. Neyses. 2003. AT2 receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway. Faseb J. 17:283-5.
Ritter, O., S. Hack, K. Schuh, N. Rothlein, A. Perrot, K.J. Osterziel, H.D. Schulte, and L. Neyses. 2002. Calcineurin in human heart hypertrophy. Circulation. 105:2265-9.
Schuh, K., S. Uldrijan, M. Telkamp, N. Rothlein, and L. Neyses. 2001. The plasmamembrane calmodulin-dependent calcium pump: a major regulator of nitric oxide synthase I. J Cell Biol. 155:201-5.
Piuhola, J., A. Hammes, K. Schuh, L. Neyses, O. Vuolteenaho, and H. Ruskoaho. 2001. Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1. Am J Physiol Regul Integr Comp Physiol. 281:R699-705.
Schuh, K., T. Twardzik, B. Kneitz, J. Heyer, A. Schimpl, and E. Serfling. 1998b. The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells. J Exp Med. 188:1369-73.
Schuh, K., B. Kneitz, J. Heyer, U. Bommhardt, E. Jankevics, F. Berberich-Siebelt, K. Pfeffer, H.K. Muller-Hermelink, A. Schimpl, and E. Serfling. 1998a. Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice. Eur J Immunol. 28:2456-66.
Hammes, A., S. Oberdorf-Maass, T. Rother, K. Nething, F. Gollnick, K.W. Linz, R. Meyer, K. Hu, H. Han, P. Gaudron, G. Ertl, S. Hoffmann, U. Ganten, R. Vetter, K. Schuh, C. Benkwitz, H.G. Zimmer, and L. Neyses. 1998. Overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats. Circ Res. 83:877-88.
Heyer, J., B. Kneitz, K. Schuh, E. Jankevics, F. Siebelt, A. Schimpl, and E. Serfling. 1997. Inefficient termination of antigen responses in NF-ATp-deficient mice. Immunobiology. 198:162-9.
Schuh, K., B. Kneitz, J. Heyer, F. Siebelt, C. Fischer, E. Jankevics, E. Rude, E. Schmitt, A. Schimpl, and E. Serfling. 1997. NF-ATp plays a prominent role in the transcriptional induction of Th2-type lymphokines. Immunol Lett. 57:171-5.
Schuh, K., A. Avots, H.P. Tony, E. Serfling, and C. Kneitz. 1996. Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients. Leuk Lymphoma. 23:583-92.