Publikationen

Medizin 1

Direktor:
Prof. Dr. med. Markus F. Neurath

Arbeitsgruppe Mukosale Immunregulation und Intestinale Zellbiologie (Prof. Dr. rer. nat. Christoph Becker)

Jahresberichte

2017

He G.-W., Günther C., Thonn V., Yu Y.-Q., Martini E., Buchen B., Neurath M.F., Stürzl M., Becker C. Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice. J Exp Med. 2017. In press. (DOI: 10.1084/jem.20160442)

Chiriac M.T., M. Mahapatro, M.F. Neurath, C. Becker. The Microbiome in Visceral Medicine: Inflammatory Bowel Disease, Obesity and Beyond. Visceral Medicine. 2017. In press (DOI: 10.1159/000470892)

Buchheister S., M. Buettner, M. Basic, A. Noack, G. Breves, B. Buchen, L.M. Keubler, C. Becker, A. Bleich. CD14 plays a protective role in experimental inflammatory bowel disease by enhancing intestinal barrier function. Am J Pathol. 2017. 187(5):1106-1120.

Chiriac M.T., Buchen B., Wandersee A., Hundorfean G., Günther G., Bourjau Y., Doyle S.E., Frey B., Ekici A.B., Büttner C., Weigmann B., Atreya R., Wirtz S., Becker C., Siebler J., Neurath M.F. Activation of epithelial STAT1 by Interleukin 28 controls mucosal healing in mice with colitis and is increased in mucosa of patients with inflammatory bowel disease. Gastroenterology. In press (dx.doi.org/10.1053/j.gastro.2017.03.015)

Martini E, S. Krug, B. Siegmund, M.F. Neurath, C. Becker. Mend your fences: The epithelial barrier and its relationship with mucosal immunity in inflammatory bowel disease. Cell Mol Gastroenterol Hepatol. 2017. In Press ( dx.doi.org/10.1016/j.jcmgh.2017.03.007)

Pfeifle R., T. Rothe, N. Ipseiz, H.U. Scherer, S. Culemann, U. Harre, J.A. Ackermann, M. Seefried, A. Kleyer, S. Uderhardt, B. Haugg, A.J.Hueber, P. Daum, G.F. Heidkamp, C. Ge, S. Böhm, A. Lux, W. Schuh, I. Magorivska, K.S. Nandakumar, E. Lönnblom, C. Becker, D. Dudziak, M. Wuhrer, Y. Rombouts, C.A. Koeleman, R. Toes, T.H. Winkler, R. Holmdahl, M. Herrmann, S. Blüml, F. Nimmerjahn, G. Schett, G. Krönke. Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease Nature Immunol.  2017. 18(1):104-113.

He, G.-W., C. Günther, A.E. Kremer, V. Thonn, K. Amann, C. Poremba, M.F. Neurath, S. Wirtz, C. Becker. PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury. Gut. 2017. 66(4):716-723.

2016

Günther C., G.-W. He, A.E. Kremer, J. Murphy, E.J. Petrie, K. Amann, P. Vandenabeele, A. Linkermann, C. Poremba, U. Schleicher, C. Dewitz, S. Krautwald, M.F. Neurath, C. Becker* and S. Wirtz*. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis. J Clin Invest. 2016. 126(11):4346-4360. *Shared senior authors

Martini E., E. Schneider, C. Neufert, M.F. Neurath, C. Becker. Survivin is a guardian of the intestinal stem cell niche and its expression is regulated by TGF-β. Cell Cycle. 2016. Oct 7:1-7.

Kistner K., N. Siklosi, A. Babes, M. Khalil, T. Selescu, K. Zimmermann, S. Wirtz, C. Becker, M.F. Neurath, P.W. Reeh, M.A. Engel. Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain. Sci Rep. 2016. 6:28621.

Mahapatro, M., Försch, S., Hefele, M., G.-W. He ,E. Giner-Ventura, T. Mchedlidze , M. Kindermann , S. Vetrano, S. Danese, C. Günther, M. F. Neurath, S. Wirtz, C. Becker. Programming of intestinal epithelial differentiation by IL-33 derived from pericryptal fibroblasts in response to systemic infection. Cell Rep. 2016. 15(8):1743-56.

Leppkes M., C. Maueröder, S. Hirth, S. Nowecki, C. Günther, U. Billmeier, S. Paulus, M. Biermann, L.E. Munoz, M. Hoffmann, D. Wildner, A.L. Croxford, A. Waisman, K. Mowen, D.E. Jenne, V. Krenn, J. Mayerle, M.M. Lerch, G. Schett, S. Wirtz, M.F. Neurath, M. Herrmann, C. Becker. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis. Nature Comm. 2016. 7:10973.

Khalil M., A. Babes, R. Lakra, S. Försch, P.W. Reeh, S. Wirtz, C. Becker, M.F. Neurath, M.A. Engel. Transient receptor potential melastatin 8 ion channel in macrophages modulates colitis through a balance-shift in TNF-alpha and interleukin-10 production. Mucosal Immunol. 2016. 9(6):1500-1513.

Martini E., N. Wittkopf, C. Günther, H. Okada, A. Watson, E. Podstawa, I. Backert, M.F. Neurath, C. Becker.  Loss of Survivin in intestinal epithelial progenitor cells leads to mitotic catastrophe and breakdown of gut immune homeostasis. Cell Rep. 2016. 14(5):1062-73.

Klionsky D.J., K. Abdelmohsen, A. Abe, M.J. Abedin, H. Abeliovich, A. Acevedo Arozena,...C. Becker… et al. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3rd edition). Autophagy. 2016. 12(1):1-222.

López-Posadas R., C. Becker, C. Günther, S. Tenzer, K. Amann, U. Billmeier, R. Atreya, G. Fiorino, S. Vetrano, S. Danese, A.B Ekici, S. Wirtz, V. Thonn, A.J.M. Watson, C. Brakebusch, M. Bergö, M.F. Neurath and I. Atreya. Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation. J Clin Invest. 2016. 126(2):611-26.

Roulis M., G. Bongers, M. Armaka, T. Salviano, Z. He, A. Singh, U. Seidler, C. Becker, J. Demengeot, G. Furtado, S.A. Lira, G. Kollias. Host and microbiota interactions are critical for development of murine Crohn's-like ileitis. Mucosal Immunology. 2016. 9(3):787-97.

Leppkes M., M.F.Neurath, M. Herrmann, C. Becker. Immune deficiency versus immune excess in Inflammatory Bowel Diseases – STAT3 as a rheo-STAT of intestinal homeostasis. J Leukoc Biol. 2016. 99(1):57-66.

Fischer A., S. Zundler, R. Atreya, T. Rath, C. Voskens, S. Hirschmann, R. Lopez-Posadas, A. Watson, C. Becker, G. Schuler, C. Neufert, I. Atreya, M.F. Neurath. Differential effects of alpha4 beta7 and GPR15 on homing of effector and regulatory T cells from patients with ulcerative colitis to the inflamed gut in vivo. Gut. 2016. 65(10):1642-64.


2015

Genua, M., C. Becker, S. Vetrano. Anti-TNF antibodies and autophagy: a hidden nexus for a successful therapeutic response?  Journal of Crohn’s and Colitis. 2015. 10(3):237-8.

Becker C., M.F. Neurath, S. Wirtz. The intestinal microbiota in inflammatory bowel disease. ILAR J. 2015. 56(2):192-204.

Murtadak, V., C. Becker, M. Stürzl. Cell Death Inhibition by KSHV. Aging-US. 2015. 7(10):750-1.

Wittkopf N., G. Pickert,  U. Billmeier, M. Mahapatro, S. Wirtz, E. Martini, M. Leppkes, M.F. Neurath, C. Becker.  Activation of intestinal epithelial Stat3 orchestrates tissue defense during gastrointestinal infection. PLOS one. 2015. 10(3):e0118401

Günther C., B. Buchen, G. He, M. Hornef, N. Torow, H. Neumann, N. Wittkopf, E. Martini, M. Basic, A. Bleich, A.J. Watson, M.F. Neurath, C. Becker.  Caspase-8 controls the gut response to microbial challenges by TNFalpha -dependent and –independent pathways. Gut. 2015. 64(4):601-610

Nalleweg, N, M.T. Chiriac, E. Podstawa, C. Lehmann, T. Rau, R. Atreya, E. Krauss, G. Hundorfean, S. Fichtner-Feigl, A. Hartmann, C. Becker, J. Mudter. IL-9 and its receptor are critically involved in the pathogenesis of ulcerative colitis. Gut. 2015. 64(5):743-55.

Kreiser S., J. Eckhardt, C. Kuhnt, M. Stein, L. Krzyzak, C. Staab, C. Tucher, I. Knippertz, C. Becker, C. Günther, A. Steinkasserer, M. Lechmann. Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo. Immunobiology. 2015. 220(2):270-9.


2014

Roulis, M., C. Nikolaou, E. Kotsaki, V. Koliaraki, K. Salpea, J. Ragoussis, E. Martini, C. Becker, H.R. Herschman, S. Vetrano,S. Danese, G. Kollias. An intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis. Proc Natl Acad Sci U S A. 2014. 111(43):E4658-67.

Takahashi, N., L. Vereecke, M.J.M. Bertrand, L. Duprez, S.B. Berger, T. Divert, A. Goncalves, M. Sze, B. Gilbert, S. Kourula, V. Goossens, S. Lefevre, C. Günther, C. Becker, J. Bertin, P.J. Gough, W. Declercq, G. van Loo, P. Vandenabeele.  RIPK1 ensures intestinal homeostasis by  protecting the epithelium against apoptosis. Nature. 2014. 513(7516):95-9.

Backert I., S.B. Koralov, S. Wirtz, V. Kitowski, U. Billmeier, E. Martini, K. Hofmann, K. Hildner, N. Wittkopf, K. Brecht, M. Waldner, K. Rajewsky, M.F. Neurath, C. Becker, C. Neufert. STAT3 activation in Th17 and Th22 cells controls IL-22 mediated epithelial host defence during infectious colitis. J Immunol. 2014. 193(7):3779-91.

Leppkes M., Roulis, M. M. F. Neurath, Kollias, G. C. Becker. The pleiotropic functions of TNF-alpha in the regulation of the intestinal epithelial response to inflammation. Int Immunol. 2014. 26(9):509-515.

Günther, C., B. Buchen, M.F. Neurath, C. Becker. Regulation and pathophysiological role of epithelial turnover in the gut. Semin Cell Dev Biol. 2014. 35C:40-50.

Wittkopf N., M.F. Neurath, C. Becker. Immune-epithelial crosstalk at the intestinal surface. J Gastroenterol. 2014. 49(3):375-87.

Eckhardt J., S. Kreiser,  M. Döbbeler, C. Nicolette, M.A. DeBenedette, I.Y. Tcherepanova, C. Ostalecki, A.J. Pommer, C. Becker, C. Günther, E. Zinser, T.W. Mak, A. Steinkasserer, M. Soluble CD83 Ameliorates Experimental Colitis in Mice. Mucosal Immunology. 2014. 7(4):1006-18.


2013

Wittkopf N., C. Günther, E. Martini, G. He, K. Amann, Y.-W. He, M. Schuchmann, M.F. Neurath. C. Becker. Cellular FLICE-Like Inhibitory Protein Secures Intestinal Epithelial Cell Survival and Immune Homeostasis by Regulating Caspase-8. Gastroenterology. 2013. 145(6):1369-79.

Bindea G., B. Mlecnik, M. Tosolini, A. Kirilovsky, M. Waldner, A.C. Obenauf, H. Angell, T. Fredriksen, L. Lafontaine, A. Berger, P. Bruneval, W.H. Fridman, C. Becker, F. Pagès, M.R. Speicher, Z. Trajanoski, J. Galon. Spatio-temporal dynamics of intratumoral cells reveal the immune landscape in human cancer. Immunity. 2013. 39(4):782-95.

Katt J., D. Schwinge, I. Sobottka, A. Quaas, E. Burandt, C. Becker, M.F. Neurath, A.W. Lohse, J. Herkel, C. Schramm.  Increased Th17 Response After Pathogen Stimulation in Patients with Primary Sclerotising Cholangitis. Hepatology. 2013. 58(3):1084-93.

Neufert C., C. Becker, Ö. Türeci, M.J. Waldner, I. Backert, K. Floh, I. Atreya, M. Leppkes, A. Jefremow, M. Vieth, R. Schneider-Stock, P. Klinger, F.R. Greten, D.W. Threadgill, U. Sahin, M.F. Neurath, Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasias through Erk-mediated hyperproliferative repair.  J Clin Invest. 2013. 123(4):1428-43.

Neumann H, Günther C, Vieth M, Grauer M, Wittkopf N, Mudter J, Becker C, Schoerner C, Atreya R, Neurath MF. Confocal Laser Endomicroscopy for In Vivo Diagnosis of Clostridium difficile Associated Colitis - A Pilot Study. PLoS One. 2013. 8(3):e58753.

Becker C., A.J. Watson, M.F.Neurath. The Intricate Role of Caspases in the Pathogenesis of Inflammatory Bowel Disease. Gastroenterology. 2013. 144(2):283-93.

Pickert G., H.-Y. Lim, A. Weigert, A. Häussler, T. Myrczek, M.J. Waldner, S. Labocha, N. Ferreiros-Bouzas, G. Geisslinger, J. Lotsch, C. Becker, B. Brüne, I. Tegeder. Inhibition of GTP cyclohydrolase attenuates tumor growth, angiogenesis and M2-like polarization of tumor associated macrophages. Int J Cancer. 2013. 132(3):591-604.

Günther C., H. Neumann, M.F. Neurath, C. Becker. Apoptosis, necrosis and necroptosis: Cell death regulation in the intestinal epithelium. Gut. 2013. 62(7):1062-71.


2012

Neumann H., N. Wittkopf, R. Atreya, C. Becker, M. Vieth, M.F. Neurath. Advanced endoscopic imaging: from the top of the fold to the single bacterium. Gastrointest Endosc. 2012. 75(6):1268-9.

Dornhoff H., C. Becker, J. Markl, J. Siebler, M.F. Neurath. A novel variant of the E3 ubiquitin ligase Smurf2 protects mice from colitis-associated colon cancer via the TGF-beta signaling pathway. Gastroenterology. 2012. 142(5):1183-1194.

Wittkopf, N., C. Günther, E..Martini, M. Waldner, M.F. Neurath and C. Becker. Lack of intestinal epithelial Atg7 affects Paneth cell granule formation but does not compromise immune homeostasis in the gut. Clin Dev Immunol. 2012. 2012:278059.

Weigmann B., N. Schughart, C. Wiebe, S. Sudowe, H. Jonuleit, L. Vogel, C. Becker, M.F. Neurath, S. Grabbe, J. Saloga, I. Bellinghausen. Allergen-induced IgE-dependent gut inflammation in a humanized mouse model of allergy. J Allergy Clin Immunol. 2012. 129(4):1126-35.

Engel M.A., M. Khalil, N. Siklosi, S.M. Mueller-Tribbensee, W.L. Neuhuber, M.F. Neurath, C. Becker, P.W. Reeh. Opposite effects of substance P and calcitonin gene-related peptide in oxazolone colitis. Dig Liver Dis. 2012. 44(1):24-9. 

Engel M., M. Khalil, S.M. Mueller-Tribbensee, C. Becker, W.L. Neuhuber, M.F. Neurath, P.W. Reeh. The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons. J Gastroenterology. 2012. 47(3):256-65.

Torzewski M., P. Wenzel, H. Kleinert, C. Becker, J. El-Masri, E. Wiese, M. Brandt, A. Pautz, L. Twardowski, E. Schmitt, T. Münzel, K. Reifenberg. Chronic Inflammatory Cardiomyopathy of Interferon γ-Overexpressing Transgenic Mice Is Mediated by Tumor Necrosis Factor-alpha. Am J Pathol. 2012. 180(1):73-81.  


2011

Günther C., E. Martini, N. Wittkopf, K. Amann, B. Weigmann, H. Neumann, M.J. Waldner, S.M. Hedrick, S. Tenzer, M.F. Neurath, C. Becker. Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature. 2011. 477(7364):335-9.

Rizzo A., M.J. Waldner, C. Stolfi, M. Sarra, D. Fina, C. Becker, M.F. Neurath, T.T. Macdonald, F. Pallone, G. Monteleone, M.C. Fantini. Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 2011. 71(24):7423-32.

 Engel M.A., A. Leffler, F. Niedermirtl, A. Babes, K. Zimmermann, M.R. Filipović, I. Izydorczyk, M. Eberhardt, T.I. Kichko, S.M. Mueller-Tribbensee, M. Khalil, N. Siklosi, C. Nau, I. Ivanović-Burmazović, W.L. Neuhuber, C. Becker, M.F. Neurath, P.W. Reeh. TRPA1 and Substance P Mediate Colitis in Mice. Gastroenterology. 2011. 141(4):1346-58.

Waldner M.J., S. Wirtz, C. Neufert, C. Becker, M.F. Neurath. Confocal laser endomicroscopy and narrow-band imaging-aided endoscopy for in vivo imaging of colitis and colon cancer in mice. Nat Protoc. 2011. 6(9):1471-81.

Engel M.A., C. Becker, P.W. Reeh, M.F. Neurath. Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut. Inflamm Bowel Dis. 2011. 17(4):1030-3.


Auswahl älterer Veröffentlichungen (2003-2010)

Neurath M.F., N. Wittkopf, A. Wlodarski, M.J. Waldner, C. Neufert, S. Wirtz, C. Günther, C. Becker. Assessment of tumor development and wound healing using endoscopic techniques in mice. Gastroenterology. 2010. 139(6):1837-1843

Chalaris A., N. Adam, C. Sina, P. Rosenstiel, J. Lehmann, P. Schirmacher, D. Hartmann, J. Cichy, O. Gawrilova, S. Schreiber, T. Jostock, V. Mathews, R. Hässler, C. Becker, M.F. Neurath, K. Reiss, P. Saftig, J. Scheller, S. Rose-John. Inflammation and Regeneration are orchestrated by the Disintegrin Metalloprotease Adam17. J. Exp. Med. 2010. 207(8):1617-24.

Neufert C, G. Pickert, Y.Zheng, N. Wittkopf, M. Warntjen, A. Nikolaev, W. Ouyang, Markus F. Neurath, C. Becker. Activation of epithelial STAT3 regulates intestinal homeostasis. Cell Cycle. 2010. 9(4):652-55

Pickert G, C. Neufert, M. Leppkes, Y. Zheng, N. Wittkopf, M. Warntjen, H.-A. Lehr, S. Hirth, B. Weigmann, S. Wirtz., W. Ouyang, M.F. Neurath, C. Becker. STAT3 links IL-22 signalling in intestinal epithelial cells to mucosal wound healing. J. Exp. Med. 2009. 206(7):1465-72.
 
Leppkes M* und C. Becker*, I.I. Ivanov, S. Hirth, S. Wirtz, C. Neufert, S. Pouly, A.J. Murphy, D.M. Valenzuela, G.D. Yancopoulos, B. Becher, D.R. Littman, Markus F. Neurath. RORgamma-Expressing Th17 cells Induce Murine Chronic Intestinal Inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology. 2009. 136(1):257-67.

Dominitzki S., M.C. Fantini, C. Neufert, A. Nikolaev, P.R. Galle, J. Scheller, G. Monteleone, S. Rose-John, M.F. Neurath, C. Becker. Cutting Edge: Trans-Signaling via the Soluble IL-6R Abrogates the Induction of FoxP3 in Naive CD4+CD25- T Cells. J Immunol. 2007. 179(4):2041-5.

Fantini M.C., S. Dominitzki, A. Rizzo, M.F. Neurath, C. Becker. In vitro generation of CD4+CD25+ regulatory cells from murine naïve T cells. Nature Protocols. 2007. 2(7):1789-94. 

Nenci A* und C. Becker*, A. Wullaert, R. Gareus, G. van Loo, S. Danese, M. Huth, A. Nikolaev, C. Neufert, B. Madison, D. Gumucio, M.F. Neurath, M. Pasparakis. Epithelial NEMO/IKK-gamma links innate immunity to chronic intestinal inflammation. Nature. 2007. 29;446(7135):55761.

Becker, C., M.C. Fantini, M.F. Neurath. High resolution colonoscopy in live mice. Nature Protocols. 2006. 1(6):2900-04.

Becker, C., H. Dornhoff, C. Neufert, M.C. Fantini, S. Wirtz, D. Strand, A. Nikolaev, H.A.Lehr, A.J. Murphy, D.M. Valenzuela, G.D. Yancopoulos, M. Karow, P.R. Galle, M.F. Neurath. IL-23 cross regulates IL-12 production in T cell dependent experimental colitis. J Immunol. 2006. 177(5):2760-4.

Becker, C., M.C. Fantini, M.F. Neurath. TGF-beta as an immune regulator in Colitis and Colon Cancer. Cytokine Growth Factor Rev. 2006. 17:97-106.

Becker, C., M.C. Fantini, S. Wirtz, A. Nikolaev , R. Kiesslich, H.A.Lehr, P.R. Galle, M.F. Neurath. In vivo imaging of colitis associated colon cancer in mice using high resolution chromoendoscopy. Gut. 2005. 54: 950-954.

Becker, C., M.C. Fantini,  H.A. Lehr, S. Wirtz, A. Nikolaev, P.R. Galle, S. Rose-John, M.F. Neurath. IL-6 signaling promotes tumor growth in colon cancer. Cell Cycle. 2005. 4(2) 35-38.
         
Becker, C., S. Wirtz, M.F. Neurath. Stepwise regulation of TH1 responses in autoimmunity: IL-12 related cytokines and their receptors. Inflamm Bowel Dis. 2005. 11(8):755-64.

Becker, C.*, M.C. Fantini*, C. Schramm, H.A. Lehr, S. Wirtz, A. Nikolaev, J. Burg, S. Strand, H. Ito, N. Nishimoto, K. Yoshizaki, T. Kishimoto, P.R. Galle,M. Blessing, S. Rose-John and M.F. Neurath. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity. 2004. 21(4): 491-501.

Fantini M.C., C. Becker, G. Monteleone, F. Pallone, P.R. Galle, M.F. Neurath. TGF-beta Induces a Regulatory Phenotype in CD4+CD25– T Cells through Foxp3 Induction and Down-Regulation of Smad7. J.Immunol. 2004. 172: 5149-5153.

Becker, C, Wirtz, S., Blessing, M., Pirhonen, J., Strand, D., Bechthold, O., Frick, J., Galle, P.R., Autenrieth, I., Neurath, M.F. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Invest. 2003. 112(5):693-706.

 

 

 
 
 
 
 
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Zusammenfassung