Universität Regensburg

Ralph Witzgall

Anschrift:

Leistungsprofil:

• Polyzystische Nierenerkrankung.
• Nagel-Patella-Syndrom.
• Nierenversagen, akut und chronisch.

• Charakterisierung von Pkd1 und Pkd2 Knockout-Mäusen.
• Herstellung neuer transgener Tiermodelle für die polyzystische Nierenerkrankung.Hemmung von Matrix-Metalloproteinasen als neuer therapeutischer Ansatz bei der polyzystischen Nierenerkrankung.
• Charakterisierung von Lmx1b Knockout-Mäusen.
• Herstellung neuer transgener Tiermodelle für das Nagel-Patella-Syndrom.Bedeutung von Lmx1b für die Entwicklung von Glomerulopathien.
• Etablierung eines ELISAs für die Messung der Clusterin-Ausscheidung im Urin.Herstellung konditionaler Knockout-Modelle zur Identifizierung neuer Therapieansätze beim Nierenversagen.

• Breites Spektrum an molekular- und zellbiologischen Methoden
• Zellkultur
• Immunhistochemie
• Lichtmikroskopie
• Elektronenmikroskopie

Publikationen:

• (1) Dummer R., G. Posseckert, F. Nestle, R. Witzgall, M. Burger, J. C. Becker, E. Schäfer, J. Wiede, W. Sebald, G. Burg. Soluble interleukin-2 receptors inhibit interleukin 2-dependent proliferation and cytotoxicity: Explanation for diminished natural killer cell activity in cutaneous T-cell lymphomas in vivo? J. Invest. Dermatology 98: 50-54 (1992) (2) Witzgall R., E. O´Leary, R. Gessner, A. J. Ouellette, J.V. Bonventre. Kid-1, a putative renal transcription factor: Regulation during ontogeny, and in response to ischemia and toxic injury. Mol. Cell. Biol. 13: 1933-1942 (1993) (3) Witzgall R., D. Brown, C. Schwarz, J.V. Bonventre. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the post-ischemic kidney. Evidence for a heterogeneous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J. Clin. Invest. 93: 2175-2188 (1994) (4) Witzgall R., R. Volk, R. Yeung, J.V. Bonventre. Genomic structure and chromosomal location of the rat gene encoding the zinc finger transcription factor Kid 1. Genomics 20: 203-209 (1994) (5) Witzgall R., E. O´Leary, A. Leaf, D. Önaldi, J.V. Bonventre. The Krüppel associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc. Natl. Acad. Sci. USA 91: 4514-4518 (1994) (6) Witzgall R., E. O´Leary, J.V. Bonventre. A mammalian expression vector for the expression of GAL4 fusion proteins with an epitope tag and histidine tail. Anal. Biochem. 223: 291-298 (1994) (7) Sapirstein A., R. A. Spech, R. Witzgall, J. V. Bonventre. Cytosolic phospholipase A2 (PLA2), but not secretory PLA2, potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells. J. Biol. Chem. 271: 21505-21513 (1996) (8) Kim S.-S., Y.-M. Chen, E. O’Leary, R. Witzgall, M. Vidal, J. V. Bonventre. A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc. Natl. Acad. Sci. USA 93: 15299-15304 (1996) (9) Bonventre J. V., J. M. Kyriakis, R. Spech, R. Witzgall, T. Force. Phospholipase A2 and lipids as potential modulators of c-Raf-1 kinase. Am. J. Ther. 3: 287-293 (1996) (10) Obermüller N., N. Gretz, W. Kriz, F. J. van der Woude, R. F. Reilly, H. Murer, J. Biber, R. Witzgall. Differentiation and cell polarity during renal cyst formation in the Han:SPRD (cy/+) rat, a model for ADPKD. Am. J. Physiol. 273: F357-F371 (1997) (11) Schaub T. P., J. Kartenbeck, J. König, O. Vogel, R. Witzgall, W. Kriz, D. Keppler. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J. Am. Soc. Nephrol. 8: 1213-1221 (1997) (12) Obermüller N., B. Kränzlin, R. Verma, N. Gretz, W. Kriz, R. Witzgall. Renal osmotic stress induced cotransporter: Expression in the newborn, adult and post ischemic rat kidney. Kidney Int. 52: 1584-1592 (1997) (13) Elser B., W. Kriz, J. V. Bonventre, C. Englert, R. Witzgall. The Krüppel-associated box (KRAB)-zinc finger protein Kid-1 and the Wilms’ tumor protein WT1, two transcriptional repressor proteins, bind to heteroduplex DNA. J. Biol. Chem. 272: 27908-27912 (1997) (14) Obermüller N., N. Gretz, W. Kriz, R. F. Reilly, R. Witzgall. The swelling -activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells. J. Clin. Invest. 101: 635-642 (1998) (15) Witzgall R., N. Obermüller, U. Bölitz, J. P. Calvet, B. D. Cowley Jr., C. Walker, W. Kriz, N. Gretz, J. V. Bonventre. Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia. Am. J. Physiol. 275: F928-F937 (1998) (16) Huang Z., B. Philippin, E. O’Leary, J. V. Bonventre, W. Kriz, R. Witzgall. Expression of the transcriptional repressor protein Kid-1 leads to the disintegration of the nucleolus. J. Biol. Chem. 274: 7640-7648 (1999) (17) Cai Y., Y. Maeda, A. Cedzich, V. E. Torres, G. Wu, T. Hayashi, T. Mochizuki, J. H. Park, R. Witzgall, S. Somlo. Identification and characterization of polycystin-2, the PKD2 gene product. J. Biol. Chem. 274: 28557-28565 (1999) (18) Obermüller N., A. R. Gallagher, Y. Cai, N. Gassler, N. Gretz, S. Somlo, R. Witzgall. The rat Pkd2 protein assumes distinct subcellular distributions in different organs. Am. J. Physiol. 277: F914-F925 (1999) (19) Gallagher A. R., A. Cedzich, N. Gretz, S. Somlo, R. Witzgall. The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton. Proc. Natl. Acad. Sci. USA 97: 4017-4022 (2000) (20) Obermüller N., B. Kränzlin, W. F. Blum, N. Gretz, R. Witzgall. An endocytosis defect as a possible cause of proteinuria in polycystic kidney disease. Am. J. Physiol. Renal Physiol. 280: F244-F253 (2001) (21) Obermüller N., N. Morente, B. Kränzlin, N. Gretz, R. Witzgall. A possible role for metalloproteinases in renal cyst development. Am. J. Physiol. Renal Physiol. 280: F540 F550 (2001) (22) Gassler, N., F. Autschbach, G. Heuschen, R. Witzgall, H. F. Otto, N. Obermüller. Expression of clusterin in Crohn’s disease of terminal ileum. Histol. Histopathol. 16: 755-762 (2001) (23) Klimaschewski, L., N. Obermüller, R. Witzgall. Regulation of clusterin expression following spinal cord injury. Cell Tissue Res. 306: 209-216 (2001) (24) Koulen P., Y. Cai, L. Geng, Y. Maeda, S. Nishimura, R. Witzgall, B. E. Ehrlich, S. Somlo. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4: 191-197 (2002) (25) Wärntges S., B. Friedrich, G. Henke, C. Duranton, P. A. Lang, S. Waldegger, R. Meyermann, D. Kuhl, E. J. Speckmann, N. Obermüller, R. Witzgall, A. F. Mack, H. J. Wagner, C. A. Wagner, S. Bröer, F. Lang. Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1. Pflügers Arch. - Eur. J. Physiol. 443: 617-624 (2002) (26) Rohr C., J. Prestel, L. Heidet, H. Hosser, W. Kriz, R. L. Johnson, C. Antignac, R. Witzgall. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J. Clin. Invest. 109: 1073-1082 (2002) (27) Obermüller N., Y. Cai, B. Kränzlin, R. B. Thomson, N. Gretz, W. Kriz, S. Somlo, R. Witzgall. Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases. J. Am. Soc. Nephrol. 13: 1855-1864 (2002) (28) Friedrich B., S. Wärntges, K. Klingel, M. Sauter, R. Kandolf, T. Risler, G. A. Müller, R. Witzgall, W. Kriz, H. J. Gröne, F. Lang. Up-regulation of the human serum and glucocorticoid-dependent kinase 1 in glomerulonephritis. Kidney Blood Press. Res. 25: 303-307 (2002) (29) Hidaka S., B. Kränzlin, N. Gretz, R. Witzgall. Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries. Cell Tissue Res. 310: 289-296 (2002) (30) Gallagher A. R., K. Schönig, N. Brown, H. Bujard, R. Witzgall. Use of the tetracycline system for inducible protein synthesis in the kidney. J. Am. Soc. Nephrol. 14: 2042-2051 (2003) (31) Wolf M. T. F., B. E. Mucha, M. Attanasio, I. Zalewski, S. M. Karle, H. P. H. Neumann, N. Rahman, B. Bader, C. A. Baldamus, E. Otto, R. Witzgall, A. Fuchshuber, F. Hildebrandt. Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains. Kidney Int. 64: 1580-1587 (2003) (32) Cai Y., G. Anyatonwu, D. Okuhara, K.-B. Lee, Z. Yu, T. Onoe, C.-L. Mei, Q. Qian, L. Geng, R. Witzgall, B. E. Ehrlich, S. Somlo. Calcium dependence of polycystin-2 channel activity is modulated by phosphorylation at Ser812. J. Biol. Chem. 279: 19987-19995 (2004) (33) Hidaka S., V. Könecke, L. Osten, R. Witzgall. PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2. J. Biol. Chem. 279: 35009 35016 (2004) (34) Karcher C., A. Fischer, A. Schweickert, E. Bitzer, S. Horie, R. Witzgall, M. Blum. Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in primary cilia. Differentiation 73: 425-432 (2005) (35) Brown J. H., M.-T. Bihoreau, S. Hoffmann, B. Kränzlin, I. Tychinskaya, N. Obermüller, D. Podlich, S. N. Boehn, P. J. Kaisaki, N. Megel, P. Danoy, R. R. Copley, J. Broxholme, R. Witzgall, M. Lathrop, N. Gretz, D. Gauguier. Missense mutation in sterile α motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat. J. Am. Soc. Nephrol. 16: 3517-3526 (2005) (36) Pelucchi B., G. Aguiari, A. Pignatelli, E. Manzati, R. Witzgall, L. del Senno, O. Belluzzi. Nonspecific cation current associated with native polycystin-2 in HEK-293 cells. J. Am. Soc. Nephrol. 17: 388-397 (2006) (37) Gallagher A. R., S. Hoffmann, N. Brown, A. Cedzich, S. Meruvu, D. Podlich, Y. Feng, V. Könecke, U. de Vries, H.-P. Hammes, N. Gretz, R. Witzgall. A truncated polycystin-2 protein causes polycystic kidney disease and retinal degeneration in transgenic rats. J. Am. Soc. Nephrol. 17: 2719-2730 (2006) (38) Banzi M., G. Aguiari, V. Trimi, A. Mangolini, P. Pinton, R. Witzgall, R. Rizzuto, L. del Senno. Polycystin-1 promotes PKCa-mediated NF-kB activation in kidney cells. Biochem. Biophys. Res. Commun. 350: 257-262 (2006) (39) Kurtz L., F. Schweda, C. de Wit, W. Kriz, R. Witzgall, R. Warth, A. Sauter, A. Kurtz, C. Wagner. Lack of connexin 40 causes displacement of renin-producing cells from afferent arterioles to the extraglomerular mesangium. J. Am. Soc. Nephrol. 18: 1103-1111 (2007) (40) Suleiman H., D. Heudobler, A.-S. Raschta, Y. Zhao, Q. Zhao, I. Hertting, H. Vitzthum, M. J. Moeller, L. B. Holzman, R. Rachel, R. Johnson, H. Westphal, A. Rascle, R. Witzgall. The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev. Biol. 304: 701-712 (2007) (41) Endele S., S. Klein, S. Richter, T. Molter, K. Amann, B. Klanke, R. Witzgall, R. L. Johnson, K. F. Hilgers, A. Winterpacht. Renal phenotype in heterozygous Lmx1b knockout mice (Lmx1b+/-) after unilateral nephrectomy. Transgenic Res. 16: 723-729 (2007) (42) Aguiari G., V. Trimi, M. Bogo, A. Mangolini, G. Szabadkai, P. Pinton, R. Witzgall, P. C. Harris, P. A. Borea, R. Rizzuto, L. del Senno. Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. Cell Prolif. 41: 554-573 (2008)

Kooperationsangebot für die Wirtschaft / Praxis:

• Therapiestudien bei der polyzystischen Nierenerkrankung
• DNA-Arrays von Nieren transgener Mäuse und induzierbaren Zellinien zur Identifizierung diagnostischer und therapeutischer Ziele bei der polyzystischen Nierenerkrankung
• Therapiestudien bei Modellen podozytärer Erkrankungen.DNA-Arrays von Nieren transgener Mäuse und induzierbaren Zellinien zur Identifizierung diagnostischer und therapeutischer Ziele bei podozytären Erkrankungen
• Morphologische und immunhistochemische Studien bei Nierenerkrankungen.Neue bildgebende Verfahren, zum Beispiel mit fluorogenen Substraten oder fluoreszierenden Proteinen

Bestehende Kooperationen: