Systemorientierte Immunologie und Entzündungsforschung

Dass der Tod Leben retten kann, ist zwar eine Binsenweisheit, für komplexe Organismen steckt dahinter jedoch ein wichtiger Schutzmechanismus. Apoptose heißt das „Selbstmordprogramm“ mit dem verletzte, alte, mutierte oder gefährliche Zellen in Geweben ausgeschaltet werden. Aber dieses Selbstmordprogramm kann auch von Krankheitserregern missbraucht werden – oder es kann außer Kontrolle geraten. Lesen Sie, wie Wissenschaftler in einer gemeinsamen Forschergruppe des Instituts für Molekulare und Klinische Immunologie der Otto-von-Guericke Universität Magdeburg und des HZI den programmierten Zelltod verstehen und nutzen wollen.

Publikationen

  • Annemann,M.; Plaza-Sirvent,C.; Schuster,M.; Katsoulis-Dimitriou,K.; Kliche,S.; Schraven,B.; Schmitz,I.; (2016). Atypical IkappaB proteins in immune cell differentiation and function. 171, 26-35 PubMed
  • Bou-Hanna,C.; Jarry,A.; Lode,L.; Schmitz,I.; Schulze-Osthoff,K.; Kury,S.; Bezieau,S.; Mosnier,J.F.; Laboisse,C.L.; (2015). Acute cytotoxicity of MIRA-1/NSC19630, a mutant p53-reactivating small molecule, against human normal and cancer cells via a caspase-9-dependent apoptosis. 359, 211-217 PubMed
  • Annemann,M.; Wang,Z.; Plaza-Sirvent,C.; Glauben,R.; Schuster,M.; Ewald,Sander F.; Mamareli,P.; Kuhl,A.A.; Siegmund,B.; Lochner,M.; Schmitz,I.; (2015). IkappaBNS Regulates Murine Th17 Differentiation during Gut Inflammation and Infection. 194 6, 2888-2898 PubMed
  • Bronietzki,A.W.; Schuster,M.; Schmitz,Ingo; (2014). Autophagy in T-cell development, activation and differentiation. Immunology and Cell Biology: 93, 25-34 PubMed
  • Cartron,M.L.; England,S.R.; Chiriac,A.I.; Josten,M.; Turner,R.; Rauter,Yvonne; Hurd,A.; Sahl,H.G.; Jones,S.; Foster,S.J.; (2014). Bactericidal activity of the human skin fatty acid cis-6-hexadecanoic acid on Staphylococcus aureus. Antimicrobial Agents and Chemotherapy: 58 7, 3599-360910986596 DOI: 10.1128/AAC.01043-13 HZI-Repositorium PubMed
  • Jeltsch,K.M.; Hu,D.; Brenner,S.; Zöller,J.; Heinz,G.A.; Nagel,D.; Vogel,K.U.; Rehage,N.; Warth,S.C.; Edelmann,S.L.; Gloury,R.; Martin,N.; Lohs,C.; Lech,M.; Stehklein,J.E.; Geerlof,A.; Kremmer,E.; Weber,A.; Anders,H.J.; Schmitz,Ingo; Schmidt-Supprian,M.; Fu,M.; Holtmann,H.; Krappmann,D.; Ruland,J.; Kallies,A.; Heikenwalder,M.; Heissmeyer,V.; (2014). Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nature Immunology: 15 11, 1079-108915292908 WEBURLS
  • Ewald,F.; Annemann,M.; Pils,Marina C.; Plaza-Sirvent,C.; Neff,F.; Erck,C.; Reinhold,D.; Schmitz,Ingo; (2014). Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice. Cell Death and Disease: 5 4, e1168 DOI: 10.1038/cddis.2014.138 HZI-Repositorium PubMed
  • Knievel,J.; Schulz,W.A.; Greife,A.; Hader,C.; Lubke,T.; Schmitz,Ingo; Albers,P.; Niegisch,G.; (2014). Multiple mechanisms mediate resistance to sorafenib in urothelial cancer. International Journal of Molecular Sciences: 15 11, 20500-20517 DOI: 10.3390/ijms151120500 HZI-Repositorium PubMed
  • Schreiber,L.; Pietzsch,Beate; Flöß,Stefan; Farah,Carla; Jänsch,Lothar; Schmitz,Ingo; Hühn,Jochen; (2014). The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-?B signaling. PLoS ONE: 9 2, e8831819326203 WEBURLS
  • Schuster,M.; Annemann,M.; Plaza-Sirvent,C.; Schmitz,Ingo; (2013). Atypical IkappaB proteins - nuclear modulators of NF-kappaB signaling. Cell Communication and Signaling: 11 1, 23 DOI: 10.1186/1478-811X-11-23 HZI-Repositorium PubMed
  • Telieps,T.; Ewald,F.; Gereke,Marcus; Annemann,Michaela; Rauter,Yvonne; Schuster,Marc; Ueffing,N.; von,Smolinski D.; Gruber,A.D.; Bruder,Dunja; Schmitz,Ingo; (2013). Cellular-FLIP, Raji isoform (c-FLIPR) modulates cell death induction upon T-cell activation and infection. European Journal of Immunology: 43 6, 1499-1510 WEBURLS
  • Schmitz,Ingo; (2013). Gadd45 Proteins in Immunity. Advances in Experimental Medicine and Biology: 793, 51-68 DOI: 10.1007/978-1-4614-8289-5_4 HZI-Repositorium PubMed
  • Hildebrand,D.G.; Alexander,E.; Horber,S.; Lehle,S.; Obermayer,K.; Munck,N.A.; Rothfuss,O.; Frick,J.S.; Morimatsu,M.; Schmitz,Ingo; Roth,J.; Ehrchen,J.M.; Essmann,F.; Schulze-Osthoff,K.; (2013). IkappaBzeta Is a Transcriptional Key Regulator of CCL2/MCP-1. Journal of Immunology: 190 9, 4812-4820 WEBURLS
  • Hocker,R.; Walker,A.; Schmitz,Ingo; (2013). Inhibition of autophagy through MAPK14-mediated phosphorylation of ATG5. 9 3, 426-428 PubMed
  • Keil,E.; Hocker,R.; Schuster,M.; Essmann,F.; Ueffing,N.; Hoffman,B.; Liebermann,D.A.; Pfeffer,K.; Schulze-Osthoff,K.; Schmitz,I.; (2013). Phosphorylation of Atg5 by the Gadd45beta-MEKK4-p38 pathway inhibits autophagy. Cell Death and Differentiation: 20 2, 321-332 DOI: 10.1038/cdd.2012.129 HZI-Repositorium PubMed
  • Schuster,M.; Glauben,R.; Plaza-Sirvent,C.; Schreiber,L.; Annemann,M.; Floess,S.; Kuhl,A.A.; Clayton,L.K.; Sparwasser,Tim; Schulze-Osthoff,K.; Pfeffer,K.; Hühn,Jochen; Siegmund,B.; Schmitz,Ingo; (2012). IkappaB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor. Immunity: 37 6, 998-1008 DOI: 10.1016/j.immuni.2012.08.023 HZI-Repositorium PubMed
  • Guerrero,A.D.; Schmitz,Ingo; Chen,M.; Wang,J.; (2012). Promotion of Caspase Activation by Caspase-9-mediated Feedback Amplification of Mitochondrial Damage. Journal of Clinical Cell Immunology: 3 3 DOI: 10.4172/2155-9899.1000126 PubMed
  • Smith,A.J.; Dai,H.; Correia,C.; Takahashi,R.; Lee,S.H.; Schmitz,Ingo*; Kaufmann,S.H.; (2011). Noxa/Bcl-2 interactions contribute to bortezomib resistance in human lymphoid cells3302. Journal of Biological Chemistry: 286 20, 17682-17692 PubMed
  • Smith AJ, Dai H, Correia C, Takahashi R, Lee SH, Schmitz I, Kaufmann SH.; (2011). Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells.. J Biol Chem: 286(20), 17682-17692 PubMed
  • Ewald,F.; Ueffing,N.; Brockmann,L.; Hader,C.; Telieps,T.; Schuster,M.; Schulz,W.A.; Schmitz,Ingo*; (2011). The role of c-FLIP splice variants in urothelial tumours. Cell Death and Disease: 2, e245 DOI: 10.1038/cddis.2011.131 HZI-Repositorium PubMed
  • Brandt,S.; Ellwanger,K.; Beuter-Gunia,C.; Schuster,M.; Hausser,A.; Schmitz,Ingo*; Beer-Hammer,S.; (2010). SLy2 targets the nuclear SAP30/HDAC1 complex. International Journal of Biochemistry and Cell Biology: 42 9, 1472-1481 PubMed
  • Emadi,Baygi M.; Soheili,Z.S.; Schmitz,Ingo*; Sameie,S.; Schulz,W.A.; (2010). Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines. Cell Biology and Toxicology: 26 6, 553-567 DOI: 10.1007/s10565-010-9163-5 HZI-Repositorium PubMed
  • Ueffing N, Singh KK, Christians A, Thorns C, Feller AC, Nagl F, Fend F, Heikaus S, Marx A, Zotz RB, Brade J, Schulz WA, Schulze-Osthoff K, Schmitz I*, Schwerk C; (2009). A SNP in the cellular FLICE-inhibitory protein (c-FLIP) gene determines protein isoform production and is associated with risk of follicular lymphoma in humans. Blood:
  • Vogler M, Weber K, Dinsdale D, Schmitz I, Schulze-Osthoff K, Dyer MJS, Cohen GM ; (2009). Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ: 16(7), 1030-1039 PubMed
  • Mersmann J, Zacharowski PA, Schmitz I, Zacharowski K; (2008). Caspase inhibitors zVAD.fmk and Q-VD-OPh fail to reduce infarct size after myocardial ischaemia and reperfusion in rodents. Resuscitation: 79(3), 468-474 PubMed
  • Hippe D, Lytovchenko O, Schmitz I, Lüder CGK ; (2008). Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop. Infect Immun: 76(7), 2905-2912 PubMed
  • Feyen O, Telieps T, Schmitz I, Niehues T ; (2008). Impaired CD95-mediated apoptosis in autoimmunity and occurrence of a p22 caspase-8 cleavage product in JIA. Klin. Pädiatrie: 220(6), 358-364 PubMed
  • Ueffing N, Keil E, Freund C, Kühne R, Schulze-Osthoff K, Schmitz I; (2008). Structural and mutational analyses of c-FLIPR, the only murine short FLIP isoform, reveal requirements for DISC recruitment. Cell Death and Differ: 15(4), 773-782 PubMed
  • Knobloch J, Schmitz I, Götz K, Schulze-Osthoff K, Rüther U; (2008). Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression and stimulation of caspase-dependent cell death. Mol Cell Biol: (2), 529-538 PubMed
  • Ueffing N, Schuster M, Keil E, Schulze-Osthoff K, Schmitz I; (2008). Upregulation of c-FLIPshort by NFAT contributes to apoptosis resistance of short-term activated T cells. Blood: 112(3), 690-698 PubMed
  • Samraj AK, Sohn D, Schulze-Osthoff K, Schmitz I; (2007). Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization. Mol Biol Cell: 18(1), 84-93 PubMed
  • Vutova P, Wirth M, Hippe D, Gross U, Schulze-Osthoff K, Schmitz I, and Lüder CGK ; (2007). Toxoplasma gondii inhibits Fas/CD95-triggered cell death by inducing aberrant processing and degradation of caspase 8. Cell Microbiol: 9(6), 1556-1570 PubMed
  • Troeger T, Schmitz I, Siepermann M, Glouchkova L, Gerdemann U, Janka-Schaub GE, Schulze-Osthoff K, Dilloo D; (2007). Upregulation of c-FLIPS+R upon CD40-stimulation is associated with inhibition of CD95-induced apoptosis in primary precursor B-ALL. Blood: 110(1), 384-387 PubMed
  • Schmitz I, Meyer C, Schulze-Osthoff K; (2006). CD95 ligand mediates T-cell receptor-induced apoptosis of a CD4+ CD8+ double positive thymic lymphoma. Oncogene: 25(58), 7587-7596 PubMed
  • Samraj AK, Keil E, Ueffing N, Schulze-Osthoff K, Schmitz I; (2006). Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95-mediated apoptosis. J Biol Chem: 281(40), 29652-29659 PubMed
  • Golks A, Brenner D, Schmitz I, Watzl C, Krueger A, Krammer PH, Lavrik I; (2006). The role of CAP3 in CD95 signaling: new insights into the mechanism of procaspase-8 activation. Cell Death and Diff: 13(3), 489-498 PubMed
  • Siegmund D, Wiscovsky A, Schmitz I, Schulze-Osthoff K, Kreuz S, Leverkus M, Dittrich-Breiholz O, Kracht M, Wajant H; (2005). Death receptor-induced signaling pathways were differentially regulated by Interferon-g upstream of caspase-8 processing. Mol Cell Biol: 25(15), 6363-6379 PubMed
  • Schmitz I, Weyd H, Krueger A, Baumann S, Fas SC, Krammer PH, Kirchhoff S; (2004). Resistance of activated T cells towards CD95-mediated apoptosis is dependent on de novo protein synthesis. J Immunol: 172(4), 2194-2000
  • Schmitz I, Clayton LK, Reinherz EL ; (2003). Gene expression analysis of thymocyte selection in vivo. Int Immunol: 15(10), 1237-1248 PubMed
  • Lavrik I, Krueger A, Schmitz I, Baumann, S, Weyd H, Krammer PH, Kirchhoff S; (2003). Letter to the Editor: Active caspase-8 tetramer is formed at the CD95 DISC. Cell Death and Diff: 10(1), 144-145 PubMed
  • Schmitz I*, Krueger A*, Baumann S, Krammer PH, Kirchhoff S; (2003). Primary Human T cells Switch from CD95-Type II to CD95-Type I cells in an IL-2 Dependent Manner. J Immunol: 171(6), 2930-2936 PubMed
  • Schmitz I, Krueger A, Baumann S, Krammer PH, Kirchhoff S; (2002). Detection of human CD95 by different antibodies. Biochem Biophys Res Commun: 297(3), 459-462 PubMed
  • Hentze H*, Schmitz I*, Latta M, Krueger A, Krammer PH, Wendel A; (2002). Glutathione dependency of caspase-8 activation at the death-inducing signaling complex (DISC). J Biol Chem: 277(7), 5588-5595 PubMed
  • Fiorini E, Schmitz I, Marissen WE, Osborn SL, Touma M, Sasada T, Reche PA, Tibaldi E, Kruisbeek AM, Reinherz EL, Clayton LK ; (2002). Peptide-induced negative selection of thymocytes activates transcription of a novel NF-kB Inhibitor protein. Mol Cell: 9(3), 637-648 PubMed
  • Eckhart,L.; Santos-Beneit,A.M.; Schmitz,I.; Krueger,A.; Fischer,H.; Bach,J.; Ban,J.; Kirchhoff,S.; Krammer,P.H.; Mollinedo,F.; Tschachler,E.; (2001). Alternative splicing of caspase-8 mRNA during differentiation of human leukocytes. Biochemical and Biophysical Research Communications: 289, 777-781
  • Krueger A, Schmitz I, Baumann S, Krammer PH, Kirchhoff S; (2001). Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex. J Biol Chem: 276(23), 20632-20640 PubMed
  • Chatterjee,D.; Schmitz,I.; Yeung,K.; Krueger,A.; Kirchhoff,S.; Krammer,P.H.; Peter,M.E.; Wyche,H.; Pantazis,P.; (2001). Induction of apoptosis in 9-nitrocampthothecin-treated DU145 human prostate carcinoma cells is increased by de novo synthesis of CD95/Cd95L and downregulation of c-FLIPshort. Cancer Research: 61, 7148-7154 Volltext HZI-Repositorium
  • Sartorius U, Schmitz I, Krammer PH ; (2001). Molecular mechanisms of death receptor-mediated apoptosis. ChemBioChem: 2(1), 20-29 PubMed
  • Holmström TH, Schmitz I, Johnson VL, Krammer PH, Chow SC, Eriksson JE; (2000). Mitogen-activated protein kinase (MAPK) signaling inhibits CD95 (Fas/APO-1)-mediated apoptosis in activated T-cells:impaired cleavage of Bid and caspase-8. EMBO J: 19(20), 5418-5428
  • Schmitz,I.; Kirchhoff,S.; Krammer,P.H.; (2000). Regulation of death receptor-mediated apoptosis pathway. Journal of Biochemistry and Cell Biology: 32, 1123-1136
  • Kirchhoff,S.; Müller,W.W.; Krueger,A.; Schmitz,I.; Krammer,P.H.; (2000). TCR-mediated Up-regulation of c-FLIP short correlates with resistance towards CD95-mediated apoptosis. Journal of Immunology: 165, 6293-6300
  • Schmitz I, Walczak H, Krammer PH, Peter ME ; (2000). The two CD95 apoptosis signaling pathways may be a way of cells to respond to different amounts and/or forms of CD95 ligand produced in different tissues. Cell Death and Differ: 7(8), 756-758
  • Scaffidi C*, Schmitz I*, Zha J, Korsmeyer SJ, Krammer PH, Peter ME ; (1999). Differential modulation of apoptosis sensitivity in CD95 type I and type II cells. J Biol Chem: 274(32), 22532-22538 PubMed
  • Keppler OT, Peter ME, Hinderlich S, Moldenhauer G, Stehling P, Schmitz I, Schwartz-Albiez R, Reutter W, Pawlita M; (1999). Differential sialylation of cell surface glycoconjugates in a human B lymphoma cell line regulates susceptibility for CD95 (APO-1/Fas)-mediated apoptosis and for infection by a lymphotropic virus. Glycobiology: 9(6), 557-569 PubMed
  • Schmitz I, Walczak H, Krammer PH, Peter ME ; (1999). Letter to the Editor: Differences between CD95 type I and type II cells detected with the CD95 ligand. Cell Death and Diff: 6(9), 821-822 PubMed
  • Scaffidi C*, Schmitz I*, Krammer PH, Peter ME; (1999). The role of c-FLIP in modulation of CD95-induced apoptosis. J Biol Chem.: 274(3), 1541-1548 PubMed

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  • Gas und Bremse für Immunantworten
    Unser Immunsystem ist geprägt durch ein kompliziertes Wechselspiel unterschiedlicher Immunzellen, das Wissenschaftler stückchenweise verstehen lernen. Um das Immunsystem daran zu hindern, dass es sich gegen uns selbst richtet oder um ihm auch mal einen Schubs geben zu können, müssen sie die molekularen Stellknöpfe finden – und beeinflussen. Einen dieser Stellknöpfe haben Ingo Schmitz und Marc Schuster entdeckt. Folgen Sie den beiden ins Labor...