Arbeitsgruppe "Thrombozyten Physiologie und Dysfunktion"

PD Dr. Kerstin Jurk

Forschungsschwerpunkte

• Regulationsmechanismen der Thrombozytenfunktion
• Thrombozytäre Signalnetzwerke
• Interaktion zwischen Thrombozyten, Leukozyten und dem vaskulärem Kompartiment in entzündungsbedingten thrombotischen Erkrankungen
• Angeborene und erworbene Thrombozytopathien

Kooperationspartner

• Prof. Dr. W. Ruf (CTH, Universitätsmedizin Mainz)
• Prof. Dr. T. Gori (II. Medizinische Klinik, Universitätsmedizin Mainz)
• Dr. C. von Auer (III. Medizinische Klinik, Universitätsmedizin Mainz, CTH Gerinnungsambulanz II)
• Prof. Dr. J. Faber, Dr. Alexandra Russo (Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz)
• Prof. Dr. H. Binder (IMBEI, Universitätsmedizin Mainz)
• PD Dr. M. Sibbing (DZHK München)
• Prof. Dr. A. Sickmann, Dr. René Zahedi (Leibniz – Institut für Analytische Wissenschaften – ISAS, Dortmund)
• Prof. Dr. B. Kehrel (Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster)
• Prof. Dr. B. Zieger (Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg)
• PD Dr. C. Kirchmaier (DKD Helios Klinik Wiesbaden)
• Prof. Dr. J. Heemskerk (CARIM, Maastricht)
• Prof. Dr. T. Hackeng (CARIM, Maastricht)
• Dr. Stepan Gambaryan (Sechenov Institute of Evolutionary physiology S. Petersburg, Russia)
• Dr. Albert Smolenski (Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Ireland)

Drittmittelförderung

• CTH TRP X3, X4
• CTH P PF
• Boehringer Ingelheim
• DFG JU 2735/2-1
• Säule B Projekt – Deutsches Zentrum für Herz-Kreislauf-Forschung e.V. (DZHK)

Team AG Jurk

Medizinische Doktoranden

• Alexandra Walter
• Anna Walther
• Tatjana Wiegand
• Johannes Irle

Ehemalige Gruppenmitglieder

• Mareike Döhrmann
• Dr. rer. nat. Elena Kumm
• Dr. rer. nat. Stephanie Makhoul
• Dr. med. Karoline Rosenplänter 
• Dr. med. vet. Katharina Trabold
• Dr. med. Alice Huang
• Dr. med. Charlotte Hutchinson
• Dr. med. phil. nat. Daniele Pillitteri

Originalarbeiten

• Ascher S, Wilms E, Pontarollo G, Kiouptsi K, Malinarich F, Kittner JM, Bosmann M, Jurk K and Reinhardt C. Response by Ascher et al to Letter Regarding Article, "Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury". Arterioscler Thromb Vasc Biol. 2021;41:e74-e75.
• Zimmer N, Krebs FK, Zimmer S, Mitzel-Rink H, Kumm EJ, Jurk K, Grabbe S, Loquai C and Tuettenberg A. Platelet-Derived GARP Induces Peripheral Regulatory T Cells-Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis. Cancers (Basel). 2020;12.
• Swieringa F, Solari FA, Pagel O, Beck F, Huang J, Feijge MAH, Jurk K, Korver-Keularts I, Mattheij NJA, Faber J, Pohlenz J, Russo A, Stumpel C, Schrander DE, Zieger B, van der Meijden PEJ, Zahedi RP, Sickmann A and Heemskerk JWM. Impaired iloprost-induced platelet inhibition and phosphoproteome changes in patients with confirmed pseudohypoparathyroidism type Ia, linked to genetic mutations in GNAS. Sci Rep. 2020;10:11389.
• Schnorbus B, Daiber A, Jurk K, Warnke S, Koenig J, Lackner KJ, Munzel T and Gori T. Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study. Eur Heart J. 2020;41:3144-3152.
• Pielsticker C, Brodde MF, Raum L, Jurk K* and Kehrel BE*. Plasmin-Induced Activation of Human Platelets Is Modulated by Thrombospondin-1, Bona Fide Misfolded Proteins and Thiol Isomerases. Int J Mol Sci. 2020;21. *Shared senior authorship.
• Neubauer K*, Jurk K*, Petermann V, Kumm E and Zieger B. Impaired Platelet Function in Sept8-Deficient Mice In Vitro. Thromb Haemost. 2020. *Shared first authorship.
• Makhoul S*, Kumm E*, Zhang P, Walter U and Jurk K. The Serine/Threonine Protein Phosphatase 2A (PP2A) Regulates Syk Activity in Human Platelets. Int J Mol Sci. 2020;21. *Shared first authorship.
• Lehwald N, Duhme C, Pinchuk I, Kirchner J, Wieferich K, Schmelzle M, Jurk K, Windmoller BA, Hubner W, Homey B, Bode J, Kubitz R, Benhidjeb T, Kruger M, Robson SC, Knoefel WT, Kehrel BE and Schulte Am Esch J. Platelets Boost Recruitment of CD133(+) Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions. Int J Mol Sci. 2020;21.
• Kumm EJ, Pagel O, Gambaryan S, Walter U, Zahedi RP, Smolenski A and Jurk K. The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets. Cells. 2020;9.
• Krueger I, Gremer L, Mangels L, Klier M, Jurk K, Willbold D, Bock HH and Elvers M. Reelin Amplifies Glycoprotein VI Activation and AlphaIIb Beta3 Integrin Outside-In Signaling via PLC Gamma 2 and Rho GTPases. Arterioscler Thromb Vasc Biol. 2020;40:2391-2403.
• Kiouptsi K, Jackel S, Wilms E, Pontarollo G, Winterstein J, Karwot C, Gross K, Jurk K and Reinhardt C. The Commensal Microbiota Enhances ADP-Triggered Integrin alphaIIbbeta3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen. Int J Mol Sci. 2020;21.
• Grill A, Kiouptsi K, Karwot C, Jurk K and Reinhardt C. Evaluation of blood collection methods and anticoagulants for platelet function analyses on C57BL/6J laboratory mice. Platelets. 2020;31:981-988.
• Döhrmann M, Makhoul S, Gross K, Krause M, Pillitteri D, von Auer C, Walter U, Lutz J, Volf I, Kehrel BE and Jurk K. CD36-fibrin interaction propagates FXI-dependent thrombin generation of human platelets. FASEB J. 2020;34:9337-9357.
• Comer S, Nagy Z, Bolado A, von Kriegsheim A, Gambaryan S, Walter U, Pagel O, Zahedi RP, Jurk K and Smolenski A. The RhoA regulators Myo9b and GEF-H1 are targets of cyclic nucleotide-dependent kinases in platelets. J Thromb Haemost. 2020;18:3002-3012.
• Bochenek ML, Leidinger C, Rosinus NS, Gogiraju R, Guth S, Hobohm L, Jurk K, Mayer E, Munzel T, Lankeit M, Bosmann M, Konstantinides S and Schafer K. Activated Endothelial TGFbeta1 Signaling Promotes Venous Thrombus Nonresolution in Mice Via Endothelin-1: Potential Role for Chronic Thromboembolic Pulmonary Hypertension. Circ Res. 2020;126:162-181.
• Ascher S, Wilms E, Pontarollo G, Formes H, Bayer F, Muller M, Malinarich F, Grill A, Bosmann M, Saffarzadeh M, Brandao I, Gross K, Kiouptsi K, Kittner JM, Lackner KJ, Jurk K and Reinhardt C. Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury. Arterioscler Thromb Vasc Biol. 2020;40:2279-2292.
• Makhoul S, Dorschel S, Gambaryan S, Walter U and Jurk K. Feedback Regulation of Syk by Protein Kinase C in Human Platelets. Int J Mol Sci. 2020;21.
• van Geffen JP, Brouns SLN, Batista J, McKinney H, Kempster C, Nagy M, Sivapalaratnam S, Baaten C, Bourry N, Frontini M, Jurk K, Krause M, Pillitteri D, Swieringa F, Verdoold R, Cavill R, Kuijpers MJE, Ouwehand WH, Downes K and Heemskerk JWM. High-throughput elucidation of thrombus formation reveals sources of platelet function variability. Haematologica. 2019;104:1256-1267.
• Trabold K*, Makhoul S*, Gambaryan S, van Ryn J, Walter U and Jurk K. The Direct Thrombin Inhibitors Dabigatran and Lepirudin Inhibit GPIbalpha-Mediated Platelet Aggregation. Thromb Haemost. 2019;119:916-929. *Shared first authorship.
• Makhoul S, Trabold K, Gambaryan S, Tenzer S, Pillitteri D, Walter U and Jurk K. cAMP- and cGMP-elevating agents inhibit GPIbalpha-mediated aggregation but not GPIbalpha-stimulated Syk activation in human platelets. Cell Commun Signal. 2019;17:122.       
• Kiouptsi K, Jackel S, Pontarollo G, Grill A, Kuijpers MJE, Wilms E, Weber C, Sommer F, Nagy M, Neideck C, Jansen Y, Ascher S, Formes H, Karwot C, Bayer F, Kollar B, Subramaniam S, Molitor M, Wenzel P, Rosenstiel P, Todorov H, Gerber S, Walter U, Jurk K, Heemskerk JWM, van der Vorst EPC, Doring Y and Reinhardt C. The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice. mBio. 2019;10.
• Hollerbach A, Muller-Calleja N, Ritter S, Hauser F, Canisius A, Orning C, Jurk K and Lackner KJ. Platelet Activation by Antiphospholipid Antibodies Depends on Epitope Specificity and is Prevented by mTOR Inhibitors. Thromb Haemost. 2019;119:1147-1153.
• Duhme C, Lehwald N, Kehrel BE, Bauchrowitz E, Ngepi A, Schmelzle M, Kolokotronis T, Benhidjeb T, Kruger M, Jurk K, Knoefel WT, Robson SC and Schulte Am Esch J. CD133(+) bone marrow stem cells (BMSC) control platelet activation - Role of ectoNTPDase-1 (CD39). Blood Cells Mol Dis. 2019;77:142-148.
• Althaus K, Zieger B, Bakchoul T, Jurk K; THROMKID-Plus Studiengruppe der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) und der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH). Standardization of Light Transmission Aggregometry for Diagnosis of Platelet Disorders: An Inter-Laboratory External Quality Assessment. Thromb Haemost. 2019;119:1154-1161.
• Urbahn MA, Kaup SC, Reusswig F, Kruger I, Spelleken M, Jurk K, Klier M, Lang PA and Elvers M. Phospholipase D1 regulation of TNF-alpha protects against responses to LPS. Sci Rep. 2018;8:10006.
• Makhoul S, Walter E, Pagel O, Walter U, Sickmann A, Gambaryan S, Smolenski A, Zahedi RP and Jurk K. Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets. Nitric Oxide. 2018;76:71-80.
• Klatt C, Kruger I, Zey S, Krott KJ, Spelleken M, Gowert NS, Oberhuber A, Pfaff L, Luckstadt W, Jurk K, Schaller M, Al-Hasani H, Schrader J, Massberg S, Stark K, Schelzig H, Kelm M and Elvers M. Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis. J Clin Invest. 2018;128:3906-3925.
• Ebert J, Wilgenbus P, Teiber JF, Jurk K, Schwierczek K, Döhrmann M, Xia N, Li H, Spiecker L, Ruf W and Horke S. Paraoxonase-2 regulates coagulation activation through endothelial tissue factor. Blood. 2018;131:2161-2172.
• Subramaniam S, Jurk K, Hobohm L, Jackel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C and Ruf W. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood. 2017;129:2291-2302.
• Steven S, Jurk K, Kopp M, Kroller-Schon S, Mikhed Y, Schwierczek K, Roohani S, Kashani F, Oelze M, Klein T, Tokalov S, Danckwardt S, Strand S, Wenzel P, Munzel T and Daiber A. Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice. Br J Pharmacol. 2017;174:1620-1632.
• Loroch S, Trabold K, Gambaryan S, Reiss C, Schwierczek K, Fleming I, Sickmann A, Behnisch W, Zieger B, Zahedi RP, Walter U and Jurk K. Alterations of the platelet proteome in type I Glanzmann thrombasthenia caused by different homozygous delG frameshift mutations in ITGA2B. Thromb Haemost. 2017;117:556-569.
• Kossmann S, Lagrange J, Jackel S, Jurk K, Ehlken M, Schonfelder T, Weihert Y, Knorr M, Brandt M, Xia N, Li H, Daiber A, Oelze M, Reinhardt C, Lackner K, Gruber A, Monia B, Karbach SH, Walter U, Ruggeri ZM, Renne T, Ruf W, Munzel T and Wenzel P. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med. 2017;9.
• Kiouptsi K, Grill A, Mann A, Dohrmann M, Lillich M, Jackel S, Malinarich F, Formes H, Manukyan D, Subramaniam S, Khandagale A, Karwot C, Thal SC, Bosmann M, Scharrer I, Jurk K and Reinhardt C. Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels. PLoS One. 2017;12:e0183590.
• Kiouptsi K, Gambaryan S, Walter E, Walter U, Jurk K and Reinhardt C. Hypoxia impairs agonist-induced integrin alphaIIbbeta3 activation and platelet aggregation. Sci Rep. 2017;7:7621.
• Jackel S, Kiouptsi K, Lillich M, Hendrikx T, Khandagale A, Kollar B, Hormann N, Reiss C, Subramaniam S, Wilms E, Ebner K, Bruhl MV, Rausch P, Baines JF, Haberichter S, Lammle B, Binder CJ, Jurk K, Ruggeri ZM, Massberg S, Walter U, Ruf W and Reinhardt C. Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2. Blood. 2017;130:542-553.
• Gowert NS, Kruger I, Klier M, Donner L, Kipkeew F, Gliem M, Bradshaw NJ, Lutz D, Kober S, Langer H, Jander S, Jurk K, Frotscher M, Korth C, Bock HH and Elvers M. Loss of Reelin protects mice against arterial thrombosis by impairing integrin activation and thrombus formation under high shear conditions. Cell Signal. 2017;40:210-221.
• Beck F, Geiger J, Gambaryan S, Solari FA, Dell'Aica M, Loroch S, Mattheij NJ, Mindukshev I, Potz O, Jurk K, Burkhart JM, Fufezan C, Heemskerk JW, Walter U, Zahedi RP and Sickmann A. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition. Blood. 2017;129:e1-e12.
• Alflen A, Prufer S, Ebner K, Reuter S, Aranda Lopez P, Scharrer I, Banno F, Stassen M, Schild H, Jurk K, Bosmann M, Beckert H and Radsak MP. ADAMTS-13 regulates neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis. Sci Rep. 2017;7:7184.
• Manukyan D, Muller-Calleja N, Jackel S, Luchmann K, Monnikes R, Kiouptsi K, Reinhardt C, Jurk K, Walter U and Lackner KJ. Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice. J Thromb Haemost. 2016;14:1011-20.

Reviews

• Lutz J, Jurk K. Platelets in Advanced Chronic Kidney Disease: Two Sides of the Coin. Semin Thromb Hemost 2020;46(3):342-356.
• Jurk K and Walter U. New Insights into Platelet Signalling Pathways by Functional and Proteomic Approaches. Hamostaseologie. 2019;39:140-151.
• Jurk K. Platelet granules - secretory and secretive. Hamostaseologie. 2017;37:208-210.
• Pagel O, Walter E, Jurk K and Zahedi RP. Taking the stock of granule cargo: Platelet releasate proteomics. Platelets. 2017;28:119-128.
• Lutz J, Jurk K and Schinzel H. Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations. Int J Nephrol Renovasc Dis. 2017;10:135-143.
• Lutz J and Jurk K. Antiplatelet Agents and Anticoagulants in Patients with Chronic Kidney Disease - from Pathophysiology to Clinical Practice. Curr Pharm Des. 2017;23:1366-1376.