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| Original research articles 57) Golomingi M, Kohler J, Lamers C, Pouw RB, Ricklin D, Dobó J, Gál P, Pál G, Kiss B, Dopler A, Schmidt CQ, Hardy ET, Lam W, Schroeder V. Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels. Front Immunol. 2023. 14:1226832 56) Moderer T, Puşcalău-Gîrţu I, Haupt C, Baur J, Rodríguez-Alfonso A, Wiese S, Schmidt CQ, Malešević M, Forssmann WG, Ständker L, Fändrich M. Human lysozyme inhibits the fibrillation of serum amyloid a protein from systemic AA amyloidosis. Amyloid. 2023. 30(4):424-433. 55) Mannes M, Pechtl V, Hafner S, Dopler A, Eriksson O, Manivel VA, Wohlgemuth L, Messerer DAC, Schrezenmeier H, Ekdahl KN, Nilsson B, Jacobsen EM, Hoenig M, Huber-Lang M, Braun CK*, Schmidt CQ*. Complement and platelets: prothrombotic cell activation requires membrane attack complex-induced release of danger signals. Blood Adv. 2023. 7(20):6367-6380. * corresponding authors 54) Li X, Wang H, Schmidt CQ, Ferreira VP, Yancopoulou D, Mastellos DC, Lambris JD, Hajishengallis G. The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms. J Immunol. 2023. 211(3):453-461. 53) van Essen MF, Peereboom ETM, Schlagwein N, van Gijlswijk-Janssen DJ, Nelemans T, Joeloemsingh JV, van den Berg CW, Prins J, Clark SJ, Schmidt CQ, Trouw LA, van Kooten C.. Preferential production and secretion of the complement regulator factor H-like protein 1 (FHL-1) by human myeloid cells. Immunobiology. 2023. 228(3):152364. 52) Mannes M, Halbgebauer R, Wohlgemuth L, Messerer DAC, Savukoski S, Schultze A, Berger B, Knapp CL, Schmidt CQ, Fürst D, Hillmer M, Siebert R, Eriksson O, Persson B, Nilsson B, Nilsson Ekdahl K, Huber-Lang M. Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance? J Innate Immun. 2023. 15(1):412-427. 51) Bechtler C, Koutsogiannaki S, Umnyakova E, Hamid A, Gautam A, Sarigiannis Y, Pouw RB, Lamers C, Rabbani S, Schmidt CQ, Lambris JD, Ricklin D. Complement-regulatory biomaterial coatings: activity and selectivity profile of the factor H-binding peptide 5C6. Acta Biomater. 2023. 155:123-138. 50) Wohlgemuth L, Stratmann AEP, Münnich F, Bernhard S, Thomaß BD, Münnich F, Mohamed AOK, Mannes M, Schmidt CQ, Nilsson Ekdahl K, Nilsson B, Fauler M, Föhr KJ, Huber-Lang M, Messerer DAC. Modulation of Neutrophil Activity by Soluble Complement Cleavage Products-An In-Depth Analysis. Cells 2022. 11(20):3297. Loacker L, Kimpel J, Bánki Z, Schmidt CQ, Griesmacher A, Anliker M. Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with SARS-CoV2 mRNA or vector vaccine. Clin Chem Lab Med. 2022. 61(1):e17-e19. 48) Barthold L, Heber S, Schmidt CQ, Gradl M, Weidinger G, Barth H, Fischer S. Human α-Defensin-6 Neutralizes Clostridioides difficile Toxins TcdA and TcdB by Direct Binding. Int J Mol Sci. 2022. 23(9):4509. 47) Nilson R, Lübbers O, Schmidt CQ, Rojewski M, Zeplin PH, Funk W, Schrezenmeier H, Kritzinger A, Kochanek S, Krutzke L. Hexon modification of human adenovirus type 5 vectors enables efficient transduction of human multipotent mesenchymal stromal cells. Mol Ther Methods Clin Dev. 2022. 25:96-110. 46) Anliker M, Drees D, Loacker L, Hafner S, Griesmacher A, Hoermann G, Fux V, Schennach H, Hörtnagl P, Dopler A, Schmidt S, Bellmann-Weiler R, Weiss G, Marx-Hofmann A, Körper S, Höchsmann B, *Schrezenmeier H, *Schmidt CQ. Upregulation of Checkpoint Ligand Programmed Death-Ligand 1 in Patients with Paroxysmal Nocturnal Hemoglobinuria Explained by Proximal Complement Activation. J Immunol. 2022. 208(5):1248-1258 * corresponding author 45) Dopler A, Zolk O, Lang SJ, Halbgebauer R, Höchsmann B, Skerra A, Braun CK, Huber-Lang MS, Schrezenmeier H, *Schmidt CQ Deregulation of Factor H by Factor H-Related Protein 1 Depends on Sialylation of Host Surfaces. Front Immunol. 2021. 12:615748. * corresponding author 44) Mannes M, Dopler A, Zolk O, Lang SJ, Halbgebauer R, Höchsmann B, Skerra A, Braun CK, Huber-Lang MS, Schrezenmeier H, *Schmidt CQ Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. Blood. 2021. 137(4):443-455. (Selected as issue highlight & plenary paper) * corresponding author 43) Zhang Y, Ghiringhelli Borsa N, Shao D, Dopler A, Jones MB, Meyer NC, Pitcher GR, Taylor AO, Nester CM, Schmidt CQ, Smith RJH. Factor H Autoantibodies and Complement-Mediated Diseases. Front Immunol. 2020. 11:607211. 42) Karasu E, Demmelmaier J, Kellermann S, Holzmann S, Köhl J, Schmidt CQ, Kalbitz M, Gebhard F, Huber-Lang MS, Halbgebauer R. Chrysosplenol Complement C5a induces Pro-inflammatory Microvesicle Shedding in Severely Injured Patients. Front Immunol. 2020. 11:1789. 41) Lang SJ, Schmiech M, Hafner S, Paetz C, Werner K, El Gaafary M, Schmidt CQ, Syrovets T, Simmet T. Chrysosplenol d, a Flavonol from Artemisia annua, Induces ERK1/2-Mediated Apoptosis in Triple Negative Human Breast Cancer Cells. Int J Mol Sci. 2020. 21(11):4090. 40) Zolk O, Hafner S, Schmidt CQ. COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments. Naunyn Schmiedebergs Arch Pharmacol. 2020. 393(7):1131-1135. 39) Harder MJ, Höchsmann B, Dopler A, Anliker M, Weinstock C, Skerra A, Simmet T, *Schrezenmeier H, *Schmidt CQ. Different Levels of Incomplete Terminal Pathway Inhibition by Eculizumab and the Clinical Response of PNH Patients. Front Immunol. 2019. 10:1639. * corresponding authors 38) Lang SJ, Schmiech M, Hafner S, Paetz C, Steinborn C, Huber R, Gaafary ME, Werner K, Schmidt CQ, Syrovets T, Simmet T. Antitumor activity of an Artemisia annua herbal preparation and identification of active ingredients. Phytomedicine. 2019. 62:152962 37) Pouw RB, Brouwer MC, de Gast M, van Beek AE, van den Heuvel LP, Schmidt CQ, van der Ende A, Sanchez-Corral P, Kuilpers TW, Wouters D. Potentiation of complement regulator Factor H protects human endothelial cells from complement attack in aHUS sera. Blood Adv. 2019. 3(4):621-632 36) Dopler A, Guntau L, Harder MJ, Palmer A, Höchsmann B, Schrezenmeier H, Simmet T, Huber-Lang M, *Schmidt CQ Self versus Nonself Discrimination by the Soluble Complement Regulators Factor H and FHL-1. J Immunol. 2019. 202(7):2082-294 (Selected as issue highlight) * corresponding author 35) Anliker M, Schmidt CQ, Harder MJ, Ganchev G, Zabern I, Höchsmann B, Schrezenmeier H, Weinstock C Complement activation by human anti-red cell antibodies: hemolytic potential of antibodies and efficacy of complement inhibitors assessed by a sensitive flow cytometric assay. Transfusion. 2018. 58(12):2992-3002 34) Schmidt CQ*, Ederveen ALH, Harder MJ, Wuhrer M, Stehle T, Blaum BS*. Biophysical analysis of sialic acid recognition by the complement regulator Factor H. Glycobiology. 2018. 28(10):765-773 * corresponding authors 33) Gruszczyk J, Kanjee U, Chan LJ, Menant S, Malleret B, Lim NTY, Schmidt CQ, Mok YF, Lin KM, Pearson RD, Rangel G, Smith BJ, Call MJ, Weekes MP, Griffin MDW, Murphy JM, Abraham J, Sriprawat K, Menezes MJ, Ferreira MU, Russell B, Renia L, Duraisingh MT, Tham WH Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax. Science. 2018. 359(6371): 48-55 32) Schmidt C, Loos C, Jin L, Schmiech M, Schmidt CQ, Gaafary ME, Syrovets T, Simmet T. Acetyl-lupeolic acid inhibits Akt signaling and induces apoptosis in chemoresistant prostate cancer cells in vitro and in vivo. Oncotarget. 2017. 8(33):55147-55161. 31) Xue X, Wu J, Ricklin D, Forneris F, Di Crescenzio P, Schmidt CQ, Granneman J, Sharp TH, Lambris JD, Gros P. Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses. Nat Struct Mol Biol. 2017. 24(8):643-651. 30) Harder MJ, Kuhn N, Schrezenmeier H, Höchsmann B, von Zabern I, Weinstock C, Simmet T, Ricklin D, Lambris JD, Skerra A, *Anliker M, *Schmidt CQ. Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood. 2017. 129(8):970-980. (Selected as issue highlight) * corresponding authors 29) Kuhn N, Schmidt CQ, Schlapschy M, Skerra A. PASylated Coversin, a C5-Specific Complement Inhibitor with Extended Pharmacokinetics, Shows Enhanced Anti-Hemolytic Activity in Vitro. Bioconjug Chem. 2016. 27(10):2359-2371. 28) J Control Release. 2016. 235:379-92. 27) *Schmidt CQ, Harder MJ, Nichols EM, Hebecker M, Anliker M, Höchsmann B, Simmet T, Csincsi ÁI, Uzonyi B, Pappworth IY, Ricklin D, Lambris JD, Schrezenmeier H, Józsi M, Marchbank KJ. Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients. Immunobiology. 2016. 221(4):503-11 * corresponding author 26) Kennedy AT, Schmidt CQ, Thompson JK, Weiss GE, Taechalertpaisarn T, Gilson PR, Barlow PN, Crabb BS, Cowman AF, Tham WH. Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection. J Immunol. 2016. 196(3):1239-48 25) Harder MJ, Anliker M, Höchsmann B, Simmet T, Huber-Lang M, Schrezenmeier H, Ricklin D, Lambris JD, Barlow PN, *Schmidt CQ. Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation. J Immunol. 2016. 196(2):866-76. * corresponding author 24) Lim NT, Harder MJ, Kennedy AT, Lin CS, Weir C, Cowman AF, Call MJ, Schmidt CQ, Tham WH. Characterization
of inhibitors and monoclonal antibodies that modulate the interaction
between Plasmodium falciparum adhesin PfRh4 with its erythrocyte
receptor complement receptor 1. Lin Z, Schmidt CQ, Koutsogiannaki S, Ricci P, Risitano AM, Lambris JD, Ricklin D. Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria. Blood. 2015. 126(7):891-4. 22) Lucas T, Benihoud K, Vigant F, Schmidt CQ, Bachem MG, Simmet T, Kochanek S. PLoS One. 2015. 10(2):e0117254. 21) El Gafaary M, Buchele B, Syrovets T, Agnolet S, Schneider B, Schmidt CQ, Simmet T. An α-Acetoxy-Tirucallic Acid Isomer Inhibits Akt/mTOR Signaling and Induces Oxidative Stress in Prostate Cancer Cells. J Pharmacol Exp Ther. 2015. 352(1):33-42. 20) J Immunol. 2014. 193(10):4962-70. 19) Park HJ, Guariento M, Maciejewski M, Hauhart R, Tham WH, Cowman AF, Schmidt CQ, Mertens HD, Liszewski MK, Hourcade DE, Barlow PN, Atkinson JP. Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor. J Biol Chem. 2014. 289(1):450-63. 18) Krauss J, Gratzl C, Sturm V, Müller C, Staudacher V, Schmidt CQ, Bracher F. Synthesis and Biological Evaluation of Novel Alkyl-Imidazolyl Carbinols and their Esters: Potent Antimycotics. Sci Pharm. 2013. 81(3):641-50. 17) Schmidt CQ, Bai H, Lin Z, Risitano AM, Barlow PN, Ricklin D, Lambris JD. Rational engineering of a minimized immune inhibitor with unique triple-targeting properties. J Immunol. 2013. 190(11):5712-21. 16) Makou E, Mertens HD, Maciejewski M, Soares DC, Matis I, Schmidt CQ, Herbert AP, Svergun DI, Barlow PN. Solution Structure of CCP Modules 10-12 Illuminates Functional Architecture of the Complement Regulator, Factor H. J Mol Biol. 2012. 424(5):295-312. 15) Goodship TH, Pappworth IY, Toth T, Denton M, Houlberg K, McCormick F, Warland D, Moore I, Hunze EM, Staniforth SJ, Hayes C, Cavalcante DP, Kavanagh D, Strain L, Herbert AP, Schmidt CQ, Barlow PN, Harris CL, Marchbank KJ. Factor H autoantibodies in membranoproliferative glomerulonephritis. Mol Immunol. 2012. 52(3-4):200-206. 14) Tetteh-Quarcoo PB, Schmidt CQ, Tham WH, Hauhart R, Mertens HD, Rowe A, Atkinson JP, Cowman AF, Rowe JA, Barlow PN. Lack of evidence from studies of soluble protein fragments that Knops blood group polymorphisms in complement receptor-type 1 are driven by malaria. PLoS One. 2012. 7(4):e34820. 13) Morgan HP, Mertens HD, Guariento M, Schmidt CQ, Soares DC, Svergun DI, Herbert AP, Barlow PN, Hannan JP. Structural analysis of the C-terminal region (modules 18-20) of complement regulator factor H (FH). PLoS One. 2012. 7(4):e34820. 12) *Tham WH, *Schmidt CQ, Hauhart RE, Guariento M, Tetteh-Quarcoo PB, Lopaticki S, Atkinson JP, Barlow PN, Cowman AF. Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes. Blood. 2011. 118(7):1923-33.
*equal
contribution *Morgan HP, *Schmidt CQ, Guariento M, Blaum BS, Gillespie D, Herbert AP, Kavanagh D, Mertens HD, Svergun DI, Johansson CM, Uhrín D, Barlow PN, Hannan JP. Structural basis for engagement by complement factor H of C3b on a self surface. Nat Struct Mol Biol. 2011. 8(4):463-70. (Selected as issue highlight)
*equal
contribution *Schmidt CQ, Slingsby FC, Richards A, *Barlow PN. Production of biologically active complement factor H in therapeutically useful quantities. Protein
Expr Purif. 2011. 76(2):254-63
* corresponding authors 9) Tham WH, Wilson DW, Lopaticki S, Schmidt CQ, Tetteh-Quarcoo PB, Barlow PN, Richard D, Corbin JE, Beeson JG, Cowman AF. Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand. Proc Natl Acad Sci U S A. 2010. 5;107(40):17327-32. 8) Dhillon B, Wright AF, Tufail A, Pappworth I, Hayward C, Moore I, Strain L, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Armbrecht AM, Laude A, Deary IJ, Staniforth SJ, Holmes LV, Goodship TH, Marchbank KJ. Complement factor h autoantibodies and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2010. 51(11):5858-63. 7) Leffler J, Herbert AP, Norström E, Schmidt CQ, Barlow PN, Blom AM, Martin M. Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells. J Biol Chem. 2010. 285(6):3766-76. 6) Moore I, Strain L, Pappworth I, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Staniforth SJ, Holmes LV, Ward R, Morgan L, Goodship TH, Marchbank KJ. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood. 2010. 115(2):379-87. 5) Schmidt CQ, Herbert AP, Mertens HD, Guariento M, Soares DC, Uhrin D, Rowe AJ, Svergun DI, Barlow PN. The central portion of factor H (modules 10-15) is compact and contains a structurally deviant CCP module. J Mol Biol. 2010. 395(1):105-22. 4) Faull PA, Florance H, Schmidt CQ, Tomczykc N, Barlow PN, Hupp TR, Nikolovad PV, Barran PE. Utilising ion-mobility mass spectrometry to interrogate macromolecules: Factor H complement control protein modules 10-15 and 19-20 and the DNA-binding core domain of tumour suppressor p53. J Mass Spectrom. 2010. 298(1-3):99-110 3) Schmidt CQ, Herbert AP, Kavanagh D, Gandy C, Fenton CJ, Blaum BS, Lyon M, Uhrín D, Barlow PN. J Immunol. 2008. 181(4):2610-9 2) Schmidt CQ, Messmer R, Bracher F, Krauss J. A New Approach to Furan-Containing Macrolactones. Turk J Chem., 2007. 31:251-256 1) Herbert AP, Deakin JA, Schmidt CQ, Blaum BS, Egan C, Ferreira VP, Pangburn MK, Lyon M, Uhrín D, Barlow PN. Structure shows that a glycosaminoglycan and protein recognition site in factor H is perturbed by age-related macular degeneration-linked single nucleotide polymorphism. J Biol Chem. 2007. 282(26):18960-8. Reviews & editorial articles 11) *Schmidt CQ, Smith RJH. Protein therapeutics and their lessons: Expect the unexpected when inhibiting the multi-protein cascade of the complement system. Immunol Rev. 2023 313(1):376-401 * corresponding author 10) *Schmidt CQ, Schrezenmeier H, Kavanagh D. Complement and the prothrombotic state. Blood. 2022. 139(13):1954-1972. * corresponding author 9) Mannes M, Schmidt CQ, Nilsson B, Ekdahl KN, Huber-Lang M. Complement as driver of systemic inflammation and organ failure in trauma, burn, and sepsis. Semin Immunopathol. 2021. 30:1-16. 8) Mannes M, Dopler A, Huber-Lang M, Schmidt CQ* Tuning the functionality by splicing: Factor H and its alternative splice variant FHL-1 share a gene but not all functions. Front Immunol. 2020. 11:596415 * corresponding author 7) Dopler A, Guntau L, Harder MJ, Palmer A, Höchsmann B, Schrezenmeier H, Simmet T, Huber-Lang M, Schmidt CQ* Response to Comment on "Self versus Nonself Discrimination by the Soluble Complement Regulators Factor H and FHL-1". J Immunol. 2019. 203(8):2029-2030 * corresponding author 6) Halbgebauer R, Schmidt CQ, Karsten CM, Ignatius A, Huber-Lang M Janus face of complement-driven neutrophil activation during sepsis. Semin Immunol. 2018. pii: S1044-5323(17)30117-3. 5) Schmidt CQ and Verschoor A Complement and coagulation: so close, yet so far. Blood. 2017. 130(24):2581-2582. 4) Schmidt CQ*, Lambris JD, Ricklin D Protection of host cells by complement regulators. Immunol Rev. 2016. 274(1):152-171. * corresponding author 3) Huber-Lang M, Gebhard F, Schmidt CQ, Palmer A, Denk S, Wiegner R Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation - closing Pandora's box? Semin Immunol. 2016. 28(3):278-84. 2) *Schmidt CQ, Kennedy AT, *Tham WH. More than just immune evasion: Hijacking complement by Plasmodium falciparum. Mol Immunol. 2015. 67(1):71-84. * corresponding authors 1) Schmidt CQ, Herbert AP, Hocking HG, Uhrín D, Barlow PN. Translational mini-review series on complement factor H: structural and functional correlations for factor H. Clin Exp Immunol. 2008. 151(1):14-24. Patent Applications 5) COMPLEMENT MODULATOR Inventors: Schmidt, Christoph; Huber-Lang, Markus; Dopler, Arthur European Patent Application No.: EP23212727.4 (Jahr: 2023) 4) COMPLEMENT INHIBITORS AND USES THEREOF Inventors: Schmidt, Christoph; Huber-Lang, Markus European Patent Application No.: EP18179269.8 (Jahr: 2018) 3) COMPLEMENT INHIBITORS AND USES THEREOF Inventors: Schmidt, Christoph; Schrezenmeier, Hubert, Anliker, Markus, Höchsmann, Britta International Application No.: PCT/EP2017/065979 2) REGULATOR OF COMPLEMENT ACTIVATION AND USES THEREOF Inventors: Lambris, John, D.; Schmidt, Christoph; Ricklin, Daniel; International Application No.: PCT/US2013/032350 1) RECOMBINANT FACTOR H AND VARIANTS AND CONJUGATES THEREOF Inventors: Schmidt, Christoph; Barlow, Paul, N.; Richards, Anna; International Application No.: PCT/GB2010/002334 Granted Patents 3) COMPLEMENT INHIBITORS AND USES THEREOF Inventors: Schmidt, Christoph; Schrezenmeier, Hubert, Anliker, Markus, Höchsmann, Britta International Application No.: PCT/EP2017/065979 (see above) publication number: EP3474883B1 publication date: 25.05.2022 2) REGULATOR OF COMPLEMENT ACTIVATION AND USES THEREOF Inventors: Lambris, John, D.; Schmidt, Christoph; Ricklin, Daniel; International Application No.: PCT/US2013/032350 (see above) publication number: US9540626 B2 publication date: 10.Jan.2017 1) RECOMBINANT CODON OPTIMISED FACTOR H Inventors: Schmidt, Christoph; Barlow, Paul, N.; Richards, Anna; International Application No.: PCT/GB2010/002334 (see above) publication number: US 8889374 B2 publication date: 18.Nov.2014 Protein data bank entries (www.pdb.org) 2JGX, 2JGW, 2KMS, 3OXU, 3SW0, 4B2R, 4B2S, 2MCZ, 2MCY |
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