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Riewald, Matthias
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Riewald, Matthias

Faculty Member
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Positions

  • - 2014 Associate Professor, Immunology and Microbial Science (IMS) , Scripps Research
Dr. Matthias Riewald studies signaling of protease-activated receptor 1 and activated protein C in blood coagulation and systemic inflammation.

Contact

  • riewald@scripps.edu

Websites

  • Matthias Riewald, M.D.
  • Riewald Laboratory
  • Publications
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Publications

recent publications

  • academic article

    • Schuepbach, R. A., Madon, J., Ender, M., Galli, P., Riewald, M. Protease-activated receptor-1 cleaved at r46 mediates cytoprotective effects Journal of Thrombosis and Haemostasis  2012 10:1675-1684  DOI:10.1111/j.1538-7836.2012.04825.x  PMID:22712885  PMCID:PMC3419798
    • Schuepbach, R. A., Velez, K., Riewald, M. Activated protein c up-regulates procoagulant tissue factor activity on endothelial cells by shedding the tfpi kunitz 1 domain Blood  2011 117:6338-6346  DOI:10.1182/blood-2010-10-316257  PMID:21474669  PMCID:PMC3122952
    • Schuepbach, R. A., Riewald, M. Coagulation factor xa cleaves protease-activated receptor-1 and mediates signaling dependent on binding to the endothelial protein c receptor Journal of Thrombosis and Haemostasis  2010 8:379-388  DOI:10.1111/j.1538-7836.2009.03682.x  PMID:19895674  PMCID:PMC3103137
    • Mosnier, L. O., Zampolli, A., Kerschen, E. J., Schuepbach, R. A., Banerjee, Y., Fernandez, J. A., Yang, X. V., Riewald, M., Weiler, H., Ruggeri, Z. M., Griffin, J. H. Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant Blood  2009 113:5970-5978  DOI:10.1182/blood-2008-10-183327  PMID:19244160  PMCID:PMC2700330
    • Schuepbach, R. A., Feistritzer, C., Fernandez, J. A., Griffin, J. H., Riewald, M. Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1 Thrombosis and Haemostasis  2009 101:724-733  DOI:10.1160/th08-10-0632  PMID:19350118  PMCID:PMC2680237
    • Schuepbach, R. A., Feistritzer, C., Brass, L. F., Riewald, M. Activated protein c-cleaved protease activated receptor-1 is retained on the endothelial cell surface even in the presence of thrombin Blood  2008 111:2667-2673  DOI:10.1182/blood-2007-09-113076  PMID:18089851  PMCID:PMC2254534
    • Feistritzer, C., Schuepbach, R. A., Mosnier, L. O., Bush, L. A., Di Cera, E., Griffin, J. H., Riewald, M. Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells Journal of Biological Chemistry  2006 281:20077-20084  DOI:10.1074/jbc.M600506200  PMID:16709569
    • Feistritzer, C., Mosheimer, B. A., Sturn, D. H., Riewald, M., Patsch, J. R., Wiedermann, C. J. Endothelial protein c receptor-dependent inhibition of migration of human lymphocytes by protein c involves epidermal growth factor receptor Journal of Immunology  2006 176:1019-1025  PMID:16393989
    • Feistritzer, C., Lenta, R., Riewald, M. Protease-activated receptors-1 and-2 can mediate endothelial barrier protection: Role in factor xa signaling Journal of Thrombosis and Haemostasis  2005 3:2798-2805  DOI:10.1111/j.1538-7836.2005.01610.x  PMID:16359518
    • Riewald, M., Ruf, W. Protease-activated receptor-1 signaling by activated protein c in cytokine-perturbed endothelial cells is distinct from thrombin signaling Journal of Biological Chemistry  2005 280:19808-19814  DOI:10.1074/jbc.M500747200  PMID:15769747
    • Feistritzer, C., Riewald, M. Endothelial barrier protection by activated protein c through par1-dependent sphingosine 1-phosphate receptor-1 crossactivation Blood  2005 105:3178-3184  DOI:10.1182/blood-2004-10-3985  PMID:15626732
    • Feistritzer, C., Mosheimer, B. A., Kaneider, N. C., Riewald, M., Patsch, J. R., Wiedermann, C. J. Thrombin affects eosinophil migration via protease-activated receptor-1 International Archives of Allergy and Immunology  2004 135:12-16  DOI:10.1159/000080037  PMID:15286440
    • Riewald, M., Ruf, W. Proteinase-activated receptor activation by coagulation proteinases Drug Development Research  2003 59:400-407  DOI:10.1002/ddr.10310
    • Ruf, W., Dorfleutner, A., Riewald, M. Specificity of coagulation factor signaling Journal of Thrombosis and Haemostasis  2003 1:1495-1503  DOI:10.1046/j.1538-7836.2003.00300.x  PMID:12871285
    • Riewald, M., Ruf, W. Science review: Role of coagulation protease cascades in sepsis Critical Care  2003 7:123-129  DOI:10.1186/cc1825  PMID:12720558  PMCID:PMC270604
    • Ruf, W., Riewald, M. Tissue factor-dependent coagulation protease signaling in acute lung injury Critical Care Medicine  2003 31:S231-S237  DOI:10.1097/01.ccm.0000057848.27456.04  PMID:12682445
    • Riewald, M., Petrovan, R. J., Donner, A., Ruf, W. Activated protein c signals through the thrombin receptor par1 in endothelial cells Journal of Endotoxin Research  2003 9:317-321  DOI:10.1179/096805103225002584  PMID:14577849
    • Riewald, M., Petrovan, R. J., Donner, A., Mueller, B. M., Ruf, W. Activation of endothelial cell protease activated receptor 1 by the protein c pathway Science  2002 296:1880-1882  DOI:10.1126/science.1071699  PMID:12052963
    • Riewald, M., Ruf, W. Orchestration of coagulation protease signaling by tissue factor Trends in Cardiovascular Medicine  2002 12:149-154  DOI:10.1016/s1050-1738(02)00153-6  PMID:12069753
    • Riewald, M., Ruf, W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor Proceedings of the National Academy of Sciences of the United States of America  2001 98:7742-7747  DOI:10.1073/pnas.141126698  PMID:11438726  PMCID:PMC35412
    • Riewald, M., Kravchenko, V. V., Petrovan, R. J., O'Brien, P. J., Brass, L. F., Ulevitch, R. J., Ruf, W. Gene induction by coagulation factor Xa is mediated by activation of protease-activated receptor 1 Blood  2001 97:3109-3116  DOI:10.1182/blood.V97.10.3109  PMID:11342437
    • Ruf, W., Fischer, E. G., Huang, H. Y., Miyagi, Y., Ott, I., Riewald, M., Mueller, B. M. Diverse functions of protease receptor tissue factor in inflammation and metastasis Immunologic Research  2000 21:289-292  DOI:10.1385/ir:21:2-3:289  PMID:10852129
    • Fischer, E. G., Riewald, M., Huang, H. Y., Miyagi, Y., Kubota, Y., Mueller, B. M., Ruf, W. Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor Journal of Clinical Investigation  1999 104:1213-1221  DOI:10.1172/jci7750  PMID:10545520
    • Riewald, M., Chuang, T., Neubauer, A., Riess, H., Schleef, R. R. Expression of bomapin, a novel human serpin, in normal/malignant hematopoiesis and in the monocytic cell lines thp-1 and aml-193 Blood  1998 91:1256-1262  PMID:9454755
    • Riewald, M., Riess, H. Treatment options for clinically recognized disseminated intravascular coagulation Seminars in Thrombosis and Hemostasis  1998 24:53-59  DOI:10.1055/s-2007-995823  PMID:9515780
    • Weisbach, V., Putzo, A., Zingsem, J., Riewald, M., Zimmermann, R., Eckstein, R., Riess, H. Leukocyte depletion and storage of single-donor platelet concentrates Vox Sanguinis  1997 72:20-25  DOI:10.1046/j.1423-0410.1997.00020.x  PMID:9031496
    • Riewald, M., Schleef, R. R. Human cytoplasmic antiproteinase neutralizes rapidly and efficiently chymotrypsin and trypsin-like proteases utilizing distinct reactive site residues Journal of Biological Chemistry  1996 271:14526-14532  PMID:8662739
    • Riewald, M., Morgenstern, K. A., Schleef, R. R. Identification and characterization of the cytoplasmic antiproteinase (cap) in human platelets - evidence for the interaction of cap with endogenous platelet proteins Journal of Biological Chemistry  1996 271:7160-7167  PMID:8636153
    • Riewald, M., Schleef, R. R. Molecular-cloning of bomapin (protease-inhibitor-10), a novel human serpin that is expressed specifically in the bone-marrow Journal of Biological Chemistry  1995 270:26754-26757  PMID:7592909
    • Himmelreich, G., Riewald, M., Rosch, R., Blumhard, G., Neuhaus, P., Roissant, R., Riess, H. Thrombomodulin - a marker for endothelial damage during orthotopic liver-transplantation American Journal of Hematology  1994 47:1-5  DOI:10.1002/ajh.2830470102  PMID:8042609
    • Riess, H., Riewald, M. The clinical impact of platelet-function testing Thrombosis Research  1994 74:S69-S78  PMID:8073403
    • Schadendorf, D., Algermissen, B., Hamann, K., Riewald, M., Nurnberger, F., Czarnetzki, B. M. Acute monoblastic leukemia with skin nodules in an adult Journal of the American Academy of Dermatology  1993 28:884-888  DOI:10.1016/0190-9622(93)70125-d  PMID:8491887
    • Riewald, M., Himmelreich, G., Breindl, P., Neuhaus, P., Riess, H. Soluble thrombomodulin levels during orthotopic liver-transplantation Seminars in Thrombosis and Hemostasis  1993 19:246-249  DOI:10.1055/s-2007-994034  PMID:8395706
    • Garibai, A. R., Rochlitz, C., Riewald, M., Oertel, J., Huhn, D. Treatment of neutropenia in feltys syndrome with granulocyte-macrophage colony-stimulating factor - hematological response accompanied by pulmonary complications with lethal outcome Annals of Hematology  1992 65:232-235  DOI:10.1007/bf01703951  PMID:1457582
    • Weisbach, V., Riess, H., Gindi, N., Zeiler, T., Riewald, M., Zingsem, J., Eckstein, R. Effects of leukocyte depletion on platelet concentrates using 2 different polyester filters Infusionstherapie und Transfusionsmedizin  1992 19:146-148  PMID:1498557
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Research

research overview

  • Protective PAR1 Signaling by the Protein C Pathway

    The serine proteases thrombin and activated protein C (APC) are major regulators of the blood coagulation system. Thrombin not only initiates fibrin formation and platelet activation but it also activates protein C on the surface of endothelial cells. The generated APC inhibits blood coagulation by downregulating prothrombin activation in a negative feedback loop. Endothelial cell protein C receptor (EPCR) can bind both protein C and APC and activation of EPCR-bound protein C is enhanced. Results from animal models and clinical trials indicate that APC has potent protective effects in systemic inflammation that are independent from its well established anticoagulant function and recombinant APC was recently approved to treat patients with severe sepsis. The molecular basis for APC's anti-inflammatory effects is incompletely understood. We have identified protease activated receptor 1 (PAR1), the prototypical thrombin receptor, and EPCR as part of a novel APC signaling pathway in endothelial cells. The G-protein-coupled PAR1 is activated by proteolytic cleavage of a specific peptide bond in the aminoterminal exodomain, leading to the exposure of a neo-aminoterminus that folds back and activates the receptor. APC binding to EPCR was required for PAR1 activation by APC and PAR1 activation accounted for all effects of APC on gene expression. Ongoing experiments in vitro and in vivo analyze how the same receptor PAR1 can mediate both proinflammatory signaling by thrombin and the important anti-inflammatory effects of APC.
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Background

education and training

  • M.D. in Medicine, Ludwig Maximilian University of Munich 1992
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Contact

full name

  • Matthias Riewald

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