NIESWANDT Gruppe

Eine Verletzung der Gefäßwand führt zur schnellen Anheftung von Blutplättchen (Thrombozyten) an der Schadensstelle, gefolgt von koagulatorischer Aktivität und der Bildung von Fibrin-haltigen Thromben, die den Schaden abdichten. Diese Prozesse sind von zentraler Bedeutung für die Blutstillung (Hämostase), können aber in erkrankten Gefäßen zum Verschluss und somit zum Infarkt in lebenswichtigen Organen führen.

Vaskuläre Biologie

Wir beschäftigen uns mit der Rolle von Oberflächenrezeptoren auf Thrombozyten und deren intrazellulären Signalwegen in der normalen Blutstillung, sowie in thrombotischen und entzündlichen Prozessen. Mit Hilfe von genetisch veränderten Mauslinien, die definierte Defekte in thrombozytären Rezeptoren oder Signalwegen aufweisen, untersuchen wir die molekularen Mechanismen, die Adhäsion, Aktivierung und Aggregation der Zellen steuern. Diese Experimente dienen als Basis für die Entwicklung neuer anti-thrombotischer Therapie-Strategien, die anschließend in Infarkt- und Entzündungsmodellen überprüft werden.

The Würzburg Platelet Group 

2018

Manukjan G, Eilenberger J, Andres O, Schambeck C, Eber S, Schulze H. Functional classification of pediatric patients with non-syndromic delta-storage pool deficiency. Hämostaseologie. 2018, manuscript in press.

Aurbach K, Spindler M, Haining EJ, Bender M, Pleines I. Blood collection, platelet isolation and measurement of platelet count and size in mice – a practical guide. Platelets. 2018, manuscript in press.

Mammadova-Bach E, Mauler M, Braun A, Duerschmied D. Autocrine and paracrine regulatory functions of platelet serotonin. Platelets. 2018 Sep;29(6):541-548. doi: 10.1080/09537104.2018.1478072.

Gorelashvili MG, Heinze KG, Stegner D. Optical Clearing of Murine Bones to Study Megakaryocytes in Intact Bone Marrow Using Light-Sheet Fluorescence Microscopy. Methods Mol Biol. 2018;1812:233-253. doi: 10.1007/978-1-4939-8585-2_14.

Mekala SR, Wörsdörfer R, Bauer J, Stoll O, Wagner N, Reeh L, Loew K, Eckner G, Kwok CK, Wischmeyer E, Dickinson ME, Schulze H, Stegner D, Benndorf RA, Edenhofer F, Pfeiffer V, Kuerten S, Frantz S, Ergün S. Generation of Cardiomyocytes From Vascular Adventitia-Resident Stem Cells. Circ Res. 2018;123:686-99.

Bender M, Otto O. No Escape-A Novel Tool to Quantify Platelet Intra-Thrombus Movements. Thromb Haemost. 2018 Aug 15. doi: 10.1055/s-0038-1668587.

Spindler M, van Eeuwijk JMM, Schurr Y, Nurden P, Nieswandt B, Stegner D, Reinhold A, Bender M. ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia. Blood. 2018 Aug 9;132(6):635-646. doi: 10.1182/blood-2018-01-829259.

Pleines I, Lebois M, Gangatirkar P, Au AE, Lane RM, Henley KJ, Kauppi M, Corbin J, Cannon P, Bernardini J, Alwis I, Jarman KE, Ellis S, Metcalf D, Jackson SP, Schoenwaelder SM, Kile BT, Josefsson EC. Intrinsic apoptosis circumvents the functional decline of circulating platelets but does not cause the storage lesion. Blood. 2018 Jul 12;132(2):197-209. doi: 10.1182/blood-2017-11-816355.

Pleines I, Cherpokova D, Bender M. Rho GTPases and their downstream effectors in megakaryocyte biology. Platelets. 2018 Jun 18:1-8. doi: 10.1080/09537104.2018.1478071.

Schulze H, Stegner D. Imaging platelet biogenesis in vivo. Res Pract Thromb Haemost. 2018 Jun 10;2(3):461-468. doi: 10.1002/rth2.12112.

Andres O, Henning K, Strauß G, Pflug A, Manukjan G, Schulze H. Diagnosis of platelet function disorders: A standardized, rational, and modular flow cytometric approach. Platelets. 2018 Jun;29(4):347-356. doi: 10.1080/09537104.2017.1386297.

Cao H, Biondo M, Lioe H, Busfield S, Rayzman V, Nieswandt B, Bork K, Harrison LC, Auyeung P, Farkas H, Csuka D, Pelzing M, Dower S, Wilson MJ, Nash A, Nolte MW, Panousis C. Antibody-mediated inhibition of FXIIa blocks downstream bradykinin generation. J Allergy Clin Immunol. 2018 Jun 21. pii: S0091-6749(18)30901-1. doi: 10.1016/j.jaci.2018.06.014.

Giles JA, Greenhalgh AD, Denes A, Nieswandt B, Coutts G, McColl BW, Allan SM.  Neutrophil infiltration to the brain is platelet-dependent, and is reversed by blockade of platelet GPIbα. Immunology. 2018 Jun;154(2):322-328. doi: 10.1111/imm.12892.

Stritt S, Birkholz I, Beck S, Sorrentino S, Sapra KT, Viaud J, Heck J, Gaits-Iacovoni F, Schulze H, Du X, Hartwig JH, Braun A, Bender M, Medalia O, Nieswandt B. Profilin 1-mediated cytoskeletal rearrangements regulate integrin function in mouse platelets. Blood Adv. 2018 May 8;2(9):1040-1045. doi:10.1182/bloodadvances.2017014001.

Pircher J, Czermak T, Ehrlich A, Eberle C, Gaitzsch E, Margraf A, Grommes J, Saha P, Titova A, Ishikawa-Ankerhold H, Stark K, Petzold T, Stocker T, Weckbach LT, Novotny J, Sperandio M, Nieswandt B, Smith A, Mannell H, Walzog B, Horst D, Soehnlein O, Massberg S, Schulz C. Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. Nat Commun. 2018 Apr 18;9(1):1523. doi: 10.1038/s41467-018-03925-2.

Gotru SK, Gil-Pulido J, Beyersdorf N, Diefenbach A, Becker IC, Vögtle T, Remer K, Chubanov V, Gudermann T, Hermanns HM, Nieswandt B, Kerkau T, Zernecke A, Braun A. Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells Dysregulates B Cell Development and Signaling in Mice. J Immunol. 2018 Apr 15;200(8):2529-2534. doi: 10.4049/jimmunol.1701467.

Nagy M, Mastenbroek TG, Mattheij NJA, de Witt S, Clemetson KJ, Kirschner J, Schulz AS, Vraetz T, Speckmann C, Braun A, Cosemans JMEM, Zieger B, Heemskerk JWM. Variable impairment of platelet functions in patients with severe, genetically linked immune deficiencies. Haematologica. 2018 Mar;103(3):540-549. doi: 10.3324/haematol.2017.176974.

Gupta S, Cherpokova D, Spindler M, Morowski M, Bender M, Nieswandt B. GPVI signaling is compromised in newly formed platelets after acute thrombocytopenia in mice. Blood. 2018 Mar 8;131(10):1106-1110. doi: 10.1182/blood-2017-08-800136.

Rayes J, Jadoui S, Lax S, Gros A, Wichaiyo S, Ollivier V, Denis CV, Ware J, Nieswandt B, Jandrot-Perrus M, Watson SP, Ho-Tin-Noé B. The contribution of platelet glycoprotein receptors to inflammatory bleeding prevention is stimulus and organ dependent. Haematologica. 2018 Jun;103(6):e256-e258. doi: 10.3324/haematol.2017.182162. Epub 2018 Feb 1.

Claushuis TAM, de Vos AF, Nieswandt B, Boon L, Roelofs JJTH, de Boer OJ, van  't Veer C, van der Poll T. Platelet glycoprotein VI aids in local immunity during pneumonia-derived sepsis caused by gram-negative bacteria. Blood. 2018 Feb 22;131(8):864-876. doi: 10.1182/blood-2017-06-788067.

Gotru SK, Chen W, Kraft P, Becker IC, Wolf K, Stritt S, Zierler S, Hermanns HM, Rao D, Perraud AL, Schmitz C, Zahedi RP, Noy PJ, Tomlinson MG, Dandekar T, Matsushita M, Chubanov V, Gudermann T, Stoll G, Nieswandt B, Braun A. TRPM7 Kinase Controls Calcium Responses in Arterial Thrombosis and Stroke in Mice. Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):344-352. doi: 10.1161/ATVBAHA.117.310391.

Cloutier N, Allaeys I, Marcoux G, Machlus KR, Mailhot B, Zufferey A, Levesque T, Becker Y, Tessandier N, Melki I, Zhi H, Poirier G, Rondina MT, Italiano JE, Flamand L, McKenzie SE, Cote F, Nieswandt B, Khan WI, Flick MJ, Newman PJ, Lacroix S, Fortin PR, Boilard E. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1550-E1559. doi: 10.1073/pnas.1720553115.

Schuhmann MK, Kraft P, Bieber M, Haarmann A, Homola GA, Pham M, Nieswandt B, Stoll G. Influence of Thrombolysis on the Safety and Efficacy of Blocking Platelet Adhesion or Secretory Activity in Acute Ischemic Stroke in Mice. Transl Stroke Res. 2018 Jan 10. doi: 10.1007/s12975-017-0606-7.

2017

Münzer P, Walker-Allgaier B, Geue S, Langhauser F, Geuss E, Stegner D, Aurbach K, Semeniak D, Chatterjee M, Gonzalez Menendez I, Märklin M, Quintanilla-Martinez L, Salih HR, Litchfield DW, Buchou T, Kleinschnitz C, Lang F, Nieswandt B, Pleines I, Schulze H, Gawaz M, Borst O. CK2β regulates thrombopoiesis and Ca(2+)-triggered platelet activation in arterial thrombosis. Blood. 2017 Dec 21;130(25):2774-2785. doi: 10.1182/blood-2017-05-784413.

Haining EJ, Matthews AL, Noy PJ, Romanska HM, Harris HJ, Pike J, Morowski M, Gavin RL, Yang J, Milhiet PE, Berditchevski F, Nieswandt B, Poulter NS, Watson SP, Tomlinson MG. Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation. Platelets. 2017 Nov;28(7):629-642. doi: 10.1080/09537104.2016.1254175.

Haining EJ, Cherpokova D, Wolf K, Becker IC, Beck S, Eble JA, Stegner D, Watson SP, Nieswandt B. CLEC-2 contributes to hemostasis independently of classical hemITAM signaling in mice. Blood. 2017 Nov 16;130(20):2224-2228. doi: 10.1182/blood-2017-03-771907.

Manukjan G, Bösing H, Schmugge M, Strauß G, Schulze H. Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome. Br J Haematol. 2017 Nov;179(4):606-617. doi: 10.1111/bjh.14913.

Beck S, Leitges M, Stegner D. Protein kinase Cι/λ is dispensable for platelet function in thrombosis and hemostasis in mice. Cell Signal. 2017 Oct;38:223-229.  doi: 10.1016/j.cellsig.2017.07.015.

Drube S, Grimlowski R, Deppermann C, Fröbel J, Kraft F, Andreas N, Stegner D, Dudeck J, Weber F, Rödiger M, Göpfert C, Drube J, Reich D, Nieswandt B, Dudeck A, Kamradt T. The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis. J Immunol. 2017 Oct 15;199(8):2948-2957. doi: 10.4049/jimmunol.1700556.

Stritt S, Beck S, Becker IC, Vögtle T, Hakala M, Heinze KG, Du X, Bender M, Braun A, Lappalainen P, Nieswandt B. Twinfilin 2a regulates platelet reactivity and turnover in mice. Blood. 2017 Oct 12;130(15):1746-1756. doi: 10.1182/blood-2017-02-770768.

Schulze H, Schlagenhauf A, Manukjan G, Beham-Schmid C, Andres O, Klopocki E, König EM, Haidl H, Panzer S, Althaus K, Muntean WE, Schwinger W, Urban C, Greinacher A, Bakchoul T, Seidel MG. Recessive grey platelet-like syndrome with unaffected erythropoiesis in the absence of the splice isoform GFI1B-p37. Haematologica. 2017 Sep;102(9):e375-e378. doi: 10.3324/haematol.2017.167957.

Stegner D, van Eeuwijk JMM, Angay O, Gorelashvili MG, Semeniak D, Pinnecker J, Schmithausen P, Meyer I, Friedrich M, Dütting S, Brede C, Beilhack A, Schulze H, Nieswandt B, Heinze KG. Thrombopoiesis is spatially regulated by the bone marrow vasculature. Nat Commun. 2017 Jul 25;8(1):127. doi: 10.1038/s41467-017-00201-7.

Dütting S, Gaits-Iacovoni F, Stegner D, Popp M, Antkowiak A, van Eeuwijk JMM, Nurden P, Stritt S, Heib T, Aurbach K, Angay O, Cherpokova D, Heinz N, Baig AA, Gorelashvili MG, Gerner F, Heinze KG, Ware J, Krohne G, Ruggeri ZM, Nurden AT, Schulze H, Modlich U, Pleines I, Brakebusch C, Nieswandt B. A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis. Nat Commun. 2017 Jun 15;8:15838. doi: 10.1038/ncomms15838.

Mammadova-Bach E, Mauler M, Braun A, Duerschmied D. Immuno-Thrombotic Effects of Platelet Serotonin. Chapter 12: Book Neuroscience "Serotonin - A Chemical Messenger Between All Types of Living Cells", 2017;10.5772/intechopen.69349.

Bender M, Stegner D, Nieswandt B. Model systems for platelet receptor shedding. Platelets. 2017 Jun;28(4):325-332. doi: 10.1080/09537104.2016.1195491.

Jamasbi J, Ayabe K, Goto S, Nieswandt B, Peter K, Siess W. Platelet receptors as therapeutic targets: Past, present and future. Thromb Haemost. 2017 Jun 28;117(7):1249-1257. doi: 10.1160/TH16-12 0911.

Andres O, Wiegering V, König EM, Schneider AL, Semeniak D, Stritt S, Klopocki E, Schulze H. A novel two-nucleotide deletion in HPS6 affects mepacrine uptake and platelet dense granule secretion in a family with Hermansky-Pudlak syndrome. Pediatr Blood Cancer. 2017 May;64(5). doi: 10.1002/pbc.26320.

Ta-Shma A, Zhang K, Salimova E, Zernecke A, Sieiro-Mosti D, Stegner D, Furtado M, Shaag A, Perles Z, Nieswandt B, Rein AJ, Rosenthal N, Neiman AM, Elpeleg O. Congenital valvular defects associated with deleterious mutations in the PLD1 gene. J Med Genet. 2017 Apr;54(4):278-286. doi: 10.1136/jmedgenet-2016-104259.

Deppermann C, Kraft P, Volz J, Schuhmann MK, Beck S, Wolf K, Stegner D, Stoll G, Nieswandt B. Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice. Blood. 2017 Mar 23;129(12):1702-1706. doi: 10.1182/blood-2016-12-750711.

Pierre S, Linke B, Suo J, Tarighi N, Del Turco D, Thomas D, Ferreiros N, Stegner D, Frölich S, Sisignano M, Meyer Dos Santos S, deBruin N, Nüsing RM, Deller T, Nieswandt B, Geisslinger G, Scholich K. GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation. J Invest Dermatol. 2017 Mar;137(3):686-695. doi: 10.1016/j.jid.2016.09.036.

Nagy M, Mastenbroek TG, Mattheij NJA, de Witt S, Clemetson KJ, Kirschner J, Schulz AS, Vraetz T, Speckmann C, Braun A, Cosemans JMEM, Zieger B, Heemskerk JWM. Variable impairment of platelet functions in patients with severe, genetically linked immune deficiencies. Haematologica. 2018 Mar;103(3):540-549. doi: 10.3324/ haematol.2017.176974.

Pleines I, Woods J, Chappaz S, Kew V, Foad N, Ballester-Beltrán J, Aurbach K,  Lincetto C, Lane RM, Schevzov G, Alexander WS, Hilton DJ, Astle WJ, Downes K, Nurden P, Westbury SK, Mumford AD, Obaji SG, Collins PW, Delerue F, Ittner LM, Bryce NS, Holliday M, Lucas CA, Hardeman EC, Ouwehand WH, Gunning PW, Turro E, Tijssen MR, Kile BT. Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017 Mar 1;127(3):814-829. doi: 10.1172/JCI86154.

Latorre-Rey LJ, Wintterle S, Dütting S, Kohlscheen S, Abel T, Schenk F, Wingert S, Rieger MA, Nieswandt B, Heinz N, Modlich U. Targeting expression to megakaryocytes and platelets by lineage-specific lentiviral vectors. J Thromb Haemost. 2017 Feb;15(2):341-355. doi: 10.1111/jth.13582.

Schuhmann MK, Guthmann J, Stoll G, Nieswandt B, Kraft P, Kleinschnitz C. Blocking of platelet glycoprotein receptor Ib reduces "thrombo-inflammation" in mice with acute ischemic stroke. J Neuroinflammation. 2017 Jan 21;14(1):18. doi: 10.1186/s12974-017-0792-y.

Vorlova S, Koch M, Manthey HD, Cochain C, Busch M, Chaudhari SM, Stegner D, Yepes M, Lorenz K, Nolte MW, Nieswandt B, Zernecke A. Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice. Thromb Haemost. 2017 Jan 5;117(1):176-187. doi: 10.1160/TH16-06-0466.

Position

Leiter - Lehrstuhl für Experimentelle Biomedizin, Schwerpunkt Vaskuläre Biologie am Rudolf-Virchow-Zentrum
Professor für Klinische Biochemie - Rudolf-Virchow-Zentrum
Mitglied - Graduate School of Life Sciences
Supervisor und Mitglied in verschiedenen Promotionskomitees - Graduate School of Life Sciences/Biomedizin 

Die Lehrveranstaltungen finden Sie hier.