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Ruf, Wolfram
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Ruf, Wolfram

Faculty Member
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Positions

  • 2017 - Professor, Immunology and Microbiology , Scripps Research
  • 2007 - Margaret Thatcher Professor of Biological Chemistry, Thrombosis Research Institute
  • 2006 - 2017 Professor, Immunology and Microbial Science (IMS) , Scripps Research
  • 2001 - 2005 Associate Professor (with tenure), Immunology and Microbial Science (IMS) , Scripps Research
  • 1996 - 2001 Associate Professor, Immunology and Microbial Science (IMS) , Scripps Research
  • 1992 - 1996 Assistant Professor, Immunology and Microbial Science (IMS) , Scripps Research
  • 1990 - 1992 Senior Research Associate, Immunology and Microbial Science (IMS) , Scripps Research
  • 1988 - 1990 Exchange Visitor, Immunology and Microbial Science (IMS) , Scripps Research
  • 1987 - 1988 Research Associate, Max Planck Society for the Advancement of Science
Dr. Wolfram Ruf studies proteins and signaling mechanisms involved in blood coagulation, angiogenesis, and inflammation in order to understand thrombophilia, hemophilia, cancer, and inflammatory diseases like sepsis.

Contact

  • ruf@scripps.edu

Websites

  • Wolfram Ruf, M.D.
  • Laboratory Website
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Publications

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    • Chakrabarty, S., Bui, Q. Y., Badeanlou, L., Hester, K., Chun, J., Ruf, W., Ciaraldi, T. P., Samad, F. S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction Adipocyte  2022 11:69-83  DOI:10.1080/21623945.2021.2021700  PMID:35094654  PMCID:PMC8803104
    • Beckmann, L., Rolling, C. C., Voigtlander, M., Mader, J., Klingler, F., Schulenkorf, A., Lehr, C., Bokemeyer, C., Ruf, W., Langer, F. Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts Cancers  2021 13  DOI:10.3390/cancers13163941  PMID:34439096  PMCID:PMC8393688
    • Hollerbach, A., Muller-Calleja, N., Pedrosa, D., Canisius, A., Sprinzl, M. F., Falter, T., Rossmann, H., Bodenstein, M., Werner, C., Sagoschen, I., Munzel, T., Schreiner, O., et al. Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19 Journal of Thrombosis and Haemostasis  2021 19:2335-2347  DOI:10.1111/jth.15455  PMID:34242469  PMCID:PMC8420426
    • Kapopara, P. R., Safikhan, N. S., Huang, J. L., Meixner, S. C., Gonzalez, K., Loghmani, H., Ruf, W., Mast, A. E., Lei, V. C., Pryzdial, E. L. G., Conway, E. M. CD248 enhances tissue factor procoagulant function, promoting arterial and venous thrombosis in mouse models Journal of Thrombosis and Haemostasis  2021  DOI:10.1111/jth.15338  PMID:33830628
    • Ruf, W. Roles of factor Xa beyond coagulation Journal of Thrombosis and Thrombolysis  2021  DOI:10.1007/s11239-021-02458-8  PMID:33893900
    • Morla, S., Deguchi, H., Fernandez, J. A., Ruf, W., Brekken, R. A., Griffin, J. H. Procoagulant activities of skeletal muscle and cardiac myosins require both myosin protein and myosinassociated anionic phospholipids Blood  2021 137:1839-1842  DOI:10.1182/blood.2020008580  PMID:33232975  PMCID:PMC8020266
    • Muller-Calleja, N., Hollerbach, A., Royce, J., Ritter, S., Pedrosa, D., Madhusudhan, T., Teifel, S., Meineck, M., Hauser, F., Canisius, A., Nguyen, T. S., Braun, J., et al. Lipid presentation by the protein C receptor links coagulation with autoimmunity Science  2021 371  DOI:10.1126/science.abc0956  PMID:33707237
    • Nevo, N., Ordonez-Moreno, L. A., Gur-Cohen, S., Avemaria, F., Bhattacharya, S., Khatib-Massalha, E., Bertagna, M., Haddad, M., Chakrabarti, P., Ruf, W., Lapidot, T., Kollet, O. Enhanced thrombin/PAR1 activity promotes G-CSF- and AMD3100-induced mobilization of hematopoietic stem and progenitor cells via NO upregulation Leukemia  2021  DOI:10.1038/s41375-021-01194-5  PMID:33654208
    • Milstone, L. M., Jackson, C., Becker, R. C., Camire, R., Knabb, R., Mann, K., Ruf, W., Wexler, R. R., Wood, J. Discussion of talks from the symposium: Factor X: From thrombokinase to oral anti-coagulants and beyond Journal of Thrombosis and Thrombolysis  2021 52:408-413  DOI:10.1007/s11239-021-02545-w  PMID:34637116  PMCID:PMC8506080
    • Ruggeri, Z. M., Ruf, W. Is VITT really a HIT Nature Immunology  2021 22:1352-1353  DOI:10.1038/s41590-021-01042-9  PMID:34686863
    • Molitor, M., Rudi, W. S., Garlapati, V., Finger, S., Schuler, R., Kossmann, S., Lagrange, J., Nguyen, T. S., Wild, J., Knopp, T., Karbach, S. H., Knorr, M., et al. Nox2(+) myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1 Cardiovascular Research  2021 117:162-177  DOI:10.1093/cvr/cvaa042  PMID:32077922
    • Kyselova, Anastasia and Elgheznawy, Amro, Wittig, Ilka and Heidler, Juliana, Mann, Alexander W., Ruf, W., Fleming, Ingrid and Randriamboavonjy, Voahanginirina Platelet-derived calpain cleaves the endothelial protease-activated receptor 1 to induce vascular inflammation in diabetes Basic Research in Cardiology  2020 115  DOI:10.1007/s00395-020-00833-9  PMID:33258989  PMCID:PMC7716944
    • Saffarzadeh, M., Grunz, K., Nguyen, T. S., Lee, Y. K., Kitano, M., Danckwardt, S., Rodrigues, C. D. S., Weiler, H., Reyda, S., Ruf, W. Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice Blood Advances  2020 4:5810-5824  DOI:10.1182/bloodadvances.2020003299  PMID:33232477  PMCID:PMC7686899
    • Sluka, S. H. M., Stampfli, S. F., Akhmedov, A., Rodewald, T. K., Sanz-Moreno, A., Horsch, M., Grest, P., Rothmeier, A. S., Rathkolb, B., Schrewe, A., Beckers, J., Neff, F., et al. Murine tissue actor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality Haematologica  2020 105:2484-2495  DOI:10.3324/haematol.2019.218818  PMID:33054088  PMCID:PMC7556672
    • Madhusudhan, T., Ghosh, S., Wang, H. J., Dong, W., Gupta, D., Elwakiel, A., Stoyanov, S., Al-Dabet, M. M., Krishnan, S., Biemann, R., Nazir, S., Zimmermann, S., et al. Podocyte Integrin- β 3 and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy Journal of the American Society of Nephrology  2020 31:1762-1780  DOI:10.1681/asn.2019111163  PMID:32709711  PMCID:PMC7460917
    • Lagrange, J., Finger, S., Kossmann, S., Garlapati, V., Ruf, W., Wenzel, P. Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice International Journal of Molecular Sciences  2020 21  DOI:10.3390/ijms21144916  PMID:32664652  PMCID:PMC7404218
    • Ruf, W., Graf, C. Coagulation signaling and cancer immunotherapy Thrombosis Research  2020 191:S106-S111  PMID:32736766
    • Kiouptsi, K., Pontarollo, G., Todorov, H., Braun, J., Jackel, S., Koeck, T., Bayer, F., Karwot, C., Karpi, A., Gerber, S., Jansen, Y., Wild, P., et al. Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice Gut Microbes  2020 11:1809-1823  DOI:10.1080/19490976.2020.1767463  PMID:32579470  PMCID:PMC7524356
    • Makhoul, S., Panova-Noeva, M., Regnault, V., Ruf, W., Wenzel, P., Lagrange, J. Rivaroxaban effects illustrate the underestimated importance of activated platelets in thrombin generation assessed by calibrated automated thrombography Journal of Clinical Medicine  2019 8  DOI:10.3390/jcm8111990
    • Graf, C., Wilgenbus, P., Pagel, S., Pott, J., Marini, F., Reyda, S., Kitano, M., Macher-Goppinger, S., Weiler, H., Ruf, W. Myeloid cell-synthesized coagulation factor X dampens antitumor immunity Science Immunology  2019 4  DOI:10.1126/sciimmunol.aaw8405  PMID:31541031
    • Koizume, S., Takahashi, T., Yoshihara, M., Nakamura, Y., Ruf, W., Takenaka, K., Miyagi, E., Miyagi, Y. Cholesterol starvation and hypoxia activate the FVII gene via the SREBP1-GILZ pathway in ovarian cancer cells to produce procoagulant microvesicles Thrombosis and Haemostasis  2019 119:1058-1071  DOI:10.1055/s-0039-1687876  PMID:31055798
    • Madhusudhan, T., Ruf, W. Coagulation signalling and metabolic disorders: lessons learned from animal models Hamostaseologie  2019 39:164-172  DOI:10.1055/s-0039-1688800  PMID:31132800
    • Rothmeier, A. S., Versteeg, H. H., Ruf, W. Factor VIIa-induced interaction with integrin controls the release of tissue factor on extracellular vesicles from endothelial cells Journal of Thrombosis and Haemostasis  2019 17:627-634  DOI:10.1111/jth.14406  PMID:30740873
    • Caminero, A., McCarville, J. L., Galipeau, H. J., Deraison, C., Bernier, S. P., Constante, M., Rolland, C., Meisel, M., Murray, J. A., Yu, X. B., Alaedini, A., Coombes, B. K., et al. Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2 Nature Communications  2019 10  DOI:10.1038/s41467-019-09037-9  PMID:30867416  PMCID:PMC6416356
    • Sutherland, M. R., Simon, A. Y., Shanina, I., Horwitz, M. S., Ruf, W., Pryzdial, E. L. G. Virus envelope tissue factor promotes infection in mice Journal of Thrombosis and Haemostasis  2019 17:482-491  DOI:10.1111/jth.14389  PMID:30659719  PMCID:PMC6397068
    • Kiouptsi, K., Ruf, W., Reinhardt, C. Microbiota-derived trimethylamine the missing jigsaw piece in thrombosis? Circulation Research  2018 123:1112-1114  DOI:10.1161/circresaha.118.314039
    • Zelaya, H., Rothmeier, A. S., Ruf, W. Tissue factor at the crossroad of coagulation and cell signaling Journal of Thrombosis and Haemostasis  2018 16:1941-1952  DOI:10.1111/jth.14246  PMID:30030891
    • Nguyen, T. S., Lapidot, T., Ruf, W. Extravascular coagulation in hematopoietic stem and progenitor cell regulation Blood  2018 132:123-131  DOI:10.1182/blood-2017-12-768986  PMID:29866813
    • Kurakula, K., Koenis, D. S., Herzik, M. A., Liu, Y. Y., Craft, J. W., van Loenen, P. B., Vos, M., Tran, M. K., Versteeg, H. H., Goumans, Mjth, Ruf, W., de Vries, C. J. M., et al. Structural and cellular mechanisms of peptidyl-prolyl isomerase Pin1-mediated enhancement of Tissue Factor gene expression, protein half-life, and pro-coagulant activity Haematologica  2018 103:1073-1082  DOI:10.3324/haematol.2017.183087
    • Ruf, W. Proteases, protease-activated receptors, and atherosclerosis Arteriosclerosis Thrombosis and Vascular Biology  2018 38:1252-1254  DOI:10.1161/atvbaha.118.311139  PMID:29793990  PMCID:PMC5976259
    • Yu, Y., Boing, A. N., Hau, C. M., Hajji, N., Ruf, W., Sturk, A., Nieuwland, R. Tissue factor coagulant activity is regulated by the plasma membrane microenvironment Thrombosis and Haemostasis  2018 118:990-1000  DOI:10.1055/s-0038-1642031  PMID:29679947
    • Ebert, J., Wilgenbus, P., Teiber, J. F., Jurk, K., Schwierczek, K., Dohrmann, M., Xia, N., Li, H., Spiecker, L., Ruf, W., Horke, S. Paraoxonase-2 regulates coagulation activation through endothelial tissue factor Blood  2018 131:2161-2172  DOI:10.1182/blood-2017-09-807040  PMID:29439952
    • Graf, C., Ruf, W. Tissue factor as a mediator of coagulation and signaling in cancer and chronic inflammation Thrombosis Research  2018 164:S143-S147  DOI:10.1016/j.thromres.2018.01.023  PMID:29703473
    • Rothmeier, A. S., Liu, E., Chakrabarty, S., Disse, J., Mueller, B. M., Ostergaard, H., Ruf, W. Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling Blood  2018 131:674-685  DOI:10.1182/blood-2017-02-768218  PMID:29246902  PMCID:PMC5805488
    • Nielsen, A. L., Sorensen, A. B., Holmberg, H. L., Gandhi, P. S., Karlsson, J., Buchardt, J., Lamberth, K., Kjelgaard-Hansen, M., Ley, C. D., Sorensen, B. B., Ruf, W., Olsen, O. H., et al. Engineering of a membrane-triggered activity switch in coagulation factor VIIa Proceedings of the National Academy of Sciences of the United States of America  2017 114:12454-12459  DOI:10.1073/pnas.1618713114  PMID:29109275  PMCID:PMC5703266
    • Kamikubo, Y., Mendolicchio, G. L., Zampolli, A., Marchese, P., Rothmeier, A. S., Orje, J. N., Gale, A. J., Krishnaswamy, S., Gruber, A., Ostergaard, H., Petersen, L. C., Ruf, W., et al. Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex Blood  2017 130:1661-1670  DOI:10.1182/blood-2017-02-767079  PMID:28729433
    • Madhusudhan, T., Wang, H., Ghosh, S., Dong, W., Kumar, V., Al-Dabet, M. M., Manoharan, J., Nazir, S., Elwakiel, A., Bock, F., Kohli, S., Marquardt, A., et al. Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin-like function Blood  2017 130:1445-1455  DOI:10.1182/blood-2017-02-767921  PMID:28687614
    • Jackel, S., Kiouptsi, K., Lillich, M., Hendrikx, T., Khandagale, A., Kollar, B., Hormann, N., Reiss, C., Subramaniam, S., Wilms, E., Ebner, K., von Bruhl, M. L., et al. Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2 Blood  2017 130:542-553  DOI:10.1182/blood-2016-11-754416  PMID:28572286
    • Rothmeier, A. S., Marchese, P., Langer, F., Kamikubo, Y., Schaffner, F., Cantor, J., Ginsberg, M. H., Ruggeri, Z. M., Ruf, W. Tissue factor prothrombotic activity is regulated by integrin-arf6 trafficking Arteriosclerosis Thrombosis and Vascular Biology  2017 37:1323-1331  DOI:10.1161/atvbaha.117.309315  PMID:28495929  PMCID:PMC5501484
    • Subramaniam, S., Jurk, K., Hobohm, L., Jackel, S., Saffarzadeh, M., Schwierczek, K., Wenzel, P., Langer, F., Reinhardt, C., Ruf, W. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development Blood  2017 129:2291-2302  DOI:10.1182/blood-2016-11-74879  PMID:28223279  PMCID:PMC5399485
    • Kossmann, S., Lagrange, J., Jackel, S., Jurk, K., Ehlken, M., Schonfelder, T., Weihert, Y., Knorr, M., Brandt, M., Xia, N., Li, H., Daiber, A., et al. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension Science Translational Medicine  2017 9  DOI:10.1126/scitranslmed.aah4923  PMID:28148841
    • Hu, Z., Cheng, J., Xu, J., Ruf, W., Lockwood, C. J. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy Angiogenesis  2017 20:85-96  DOI:10.1007/s10456-016-9530-9  PMID:27807692  PMCID:PMC5306358
    • Tieken, C., Verboom, M. C., Ruf, W., Gelderblom, H., Bovee, J. V., Reitsma, P. H., Cleton-Jansen, A. M., Versteeg, H. H. Tissue factor associates with survival and regulates tumour progression in osteosarcoma Thrombosis and Haemostasis  2016 115:1025-1033  DOI:10.1160/th15-07-0541  PMID:26763081
    • Ruf, W., Rothmeier, A. S., Graf, C. Targeting clotting proteins in cancer therapy - progress and challenges Thrombosis Research  2016 140:S1-S7  PMID:27067961
    • Koizume, S., Ito, S., Yoshioka, Y., Kanayama, T., Nakamura, Y., Yoshihara, M., Yamada, R., Ochiya, T., Ruf, W., Miyagi, E., Hirahara, F., Miyagi, Y. High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors Thrombosis and Haemostasis  2016 115:299-310  DOI:10.1160/th15-03-0213  PMID:26446354
    • Howard, B. M., Miyazawa, B. Y., Dong, W., Cedron, W. J., Vilardi, R. F., Ruf, W., Cohen, M. J. The tissue factor pathway mediates both activation of coagulation and coagulopathy after injury Journal of Trauma and Acute Care Surgery  2015 79:1009-1013  DOI:10.1097/ta.0000000000000707  PMID:26317815
    • Liang, H. P. H., Kerschen, E. J., Basu, S., Hernandez, I., Zogg, M., Jia, S., Hessner, M. J., Toso, R., Rezaie, A. R., Fernandez, J. A., Camire, R. M., Ruf, W., et al. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice Blood  2015 126:2415-2423  DOI:10.1182/blood-2015-05-644401  PMID:26341257  PMCID:PMC4653768
    • Jacobsen, C., Oechsle, K., Hauschild, J., Steinemann, G., Spath, B., Bokemeyer, C., Ruf, W., Honecker, F., Langer, F. Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy Thrombosis Research  2015 136:673-681  DOI:10.1016/j.thromres.2015.07.002  PMID:26205155
    • van der Meijden, P. E. J., Ozaki, Y., Ruf, W., de Laat, B., Mutch, N., Diamond, S., Nieuwland, R., Peters, T. C., Heestermans, M., Kremers, R. M. W., Moorlag, M., Boender, J., et al. Theme 1: Pathogenesis of venous thromboembolism (and post-thrombotic syndrome) Thrombosis Research  2015 136:S3-S7  DOI:10.1016/j.thromres.2015.07.034  PMID:26387733
    • Ruf, W., Samad, F. Tissue factor pathways linking obesity and inflammation Hamostaseologie  2015 35:279-283  DOI:10.5482/hamo-14-11-0068  PMID:25623940  PMCID:PMC4516700
    • Liang, H. P. H., Kerschen, E. J., Hernandez, I., Basu, S., Zogg, M., Botros, F., Jia, S., Hessner, M. J., Griffin, J. H., Ruf, W., Weiler, H. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice Blood  2015 125:2845-2854  DOI:10.1182/blood-2014-11-610717  PMID:25733582  PMCID:PMC4424632
    • Rothmeier, A. S., Marchese, P., Petrich, B. G., Furlan-Freguia, C., Ginsberg, M. H., Ruggeri, Z. M., Ruf, W. Caspase-1-mediated pathway promotes generation of thromboinflammatory microparticles Journal of Clinical Investigation  2015 125:1471-1484  DOI:10.1172/jci79329  PMID:25705884
    • Wang, J., Chakrabarty, S., Bui, Q., Ruf, W., Samad, F. Hematopoietic tissue factor-protease-activated receptor 2 signaling promotes hepatic inflammation and contributes to pathways of gluconeogenesis and steatosis in obese mice American Journal of Pathology  2015 185:524-535  DOI:10.1016/j.ajpath.2014.10.008  PMID:25476527  PMCID:PMC4305186
    • Tinholt, M., Stavik, B., Louch, W., Carlson, C. R., Sletten, M., Ruf, W., Skretting, G., Sandset, P. M., Iversen, N. Syndecan-3 and TFPI colocalize on the surface of endothelial-, smooth muscle-, and cancer cells PLoS One  2015 10:e0117404  DOI:10.1371/journal.pone.0117404  PMID:25617766  PMCID:PMC4305309
    • Cohen, S. G., Itkin, T., Chakrabarty, S., Graf, C., Kollet, O., Ludin, A., Golan, K., Kalinkovich, A., Ledergor, G., Wong, E., Niemeyer, E., Porat, Z., et al. PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells Nature Medicine  2015 21:1307-1317  DOI:10.1038/nm.3960  PMID:26457757  PMCID:PMC4776769
    • Sluka, S. H. M., Akhmedov, A., Vogel, J., Unruh, D., Bogdanov, V. Y., Camici, G. G., Luscher, T. F., Ruf, W., Tanner, F. C. Alternatively spliced tissue factor is not sufficient for embryonic development PLoS One  2014 9:e97793  DOI:10.1371/journal.pone.0097793  PMID:24879059  PMCID:PMC4039448
    • Ruf, W., Schaffner, F. Role of the protein C receptor in cancer progression Thrombosis Research  2014 133:S85-S89  DOI:10.1016/S0049-3848(14)50014-X  PMID:24862151  PMCID:PMC4270345
    • Pryzdial, E. L. G., Sutherland, M. R., Ruf, W. The procoagulant envelope virus surface: contribution to enhanced infection Thrombosis Research  2014 133:S15-S17  DOI:10.1016/j.thromres.2014.03.010  PMID:24759132  PMCID:PMC4440795
    • Langer, F., Ruf, W. Synergies of phosphatidylserine and protein disulfide isomerase in tissue factor activation Thrombosis and Haemostasis  2014 111:590-597  DOI:10.1160/th13-09-0802  PMID:24452853
    • Ruf, W. FXa takes center stage in vascular inflammation Blood  2014 123:1630-1631  DOI:10.1182/blood-2014-02-553081  PMID:24627521
    • Unruh, D., Turner, K., Srinivasan, R., Kocaturk, B., Qi, X., Chu, Z., Aronow, B. J., Plas, D. R., Gallo, C. A., Kalthoff, H., Kirchhofer, D., Ruf, W., et al. Alternatively spliced tissue factor contributes to tumor spread and activation of coagulation in pancreatic ductal adenocarcinoma International Journal of Cancer  2014 134:9-20  DOI:10.1002/ijc.28327  PMID:23754313  PMCID:PMC4122306
    • Yokota, N., Zarpellon, A., Chakrabarty, S., Bogdanov, V. Y., Gruber, A., Castellino, F. J., Mackman, N., Ellies, L. G., Weiler, H., Ruggeri, Z. M., Ruf, W. Contributions of thrombin targets to tissue factor-dependent metastasis in hyperthrombotic mice Journal of Thrombosis and Haemostasis  2014 12:71-81  DOI:10.1111/jth.12442  PMID:24175924  PMCID:PMC3947224
    • Samad, F., Ruf, W. Inflammation, obesity, and thrombosis Blood  2013 122:3415-3422  DOI:10.1182/blood-2013-05-427708  PMID:24092932  PMCID:PMC3829115
    • Versteeg, H. H., Ruf, W. New helpers in TF-dependent migration Journal of Thrombosis and Haemostasis  2013 11:1877-1879  DOI:10.1111/jth.12378  PMID:23941045
    • Kocaturk, B., Van den Berg, Y. W., Tiekena, C., Mieog, J. S. D., de Kruijf, E. M., Engels, C. C., van der Ent, M. A., Kuppen, P. J., Van De Velde, C. J., Ruf, W., Reitsma, P. H., Osanto, S., et al. Alternatively spliced tissue factor promotes breast cancer growth in a beta 1 integrin-dependent manner Proceedings of the National Academy of Sciences of the United States of America  2013 110:11517-11522  DOI:10.1073/pnas.1307100110  PMID:23801760  PMCID:PMC3710867
    • Schaffner, F., Yokota, N., Carneiro-Lobo, T., Kitano, M., Schaffer, M., Anderson, G. M., Mueller, B. M., Esmon, C. T., Ruf, W. Endothelial protein C receptor function in murine and human breast cancer development PLoS One  2013 8:e61071  DOI:10.1371/journal.pone.0061071  PMID:23593394  PMCID:PMC3621887
    • von Drygalski, A., Furlan-Freguia, C., Ruf, W., Griffin, J. H., Mosnier, L. O. Organ-specific protection against lipopolysaccharide-induced vascular leak is dependent on the endothelial protein C receptor Arteriosclerosis, Thrombosis, and Vascular Biology  2013 33:769-776  DOI:10.1161/atvbaha.112.301082  PMID:23393392
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    • 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
    • Bergum, P. W., Cruikshank, A., Maki, S. L., Kelly, C. R., Ruf, W., Vlasuk, G. P. Role of zymogen and activated factor x as scaffolds for the inhibition of the blood coagulation factor viia-tissue factor complex by recombinant nematode anticoagulant protein c2 Journal of Biological Chemistry  2001 276:10063-10071  DOI:10.1074/jbc.M009116200  PMID:11139576
    • Petrovan, R. J., Ruf, W. Residue met(156) contributes to the labile enzyme conformation of coagulation factor viia Journal of Biological Chemistry  2001 276:6616-6620  DOI:10.1074/jbc.M004726200  PMID:11078728
    • Iakhiaev, A., Ruf, W., Rao, L. V. M. The role of catalytic cleft and exosite residues of factor viia for complex formation with tissue factor pathway inhibitor Thrombosis and Haemostasis  2001 85:458-463  PMID:11307815
    • Ruf, W. Molecular regulation of blood clotting in tumor biology Haemostasis  2001 31:5-7  PMID:11990479
    • Petrovan, R. J., Ruf, W. Role of residue phe(225) in the cofactor-mediated, allosteric regulation of the serine protease coagulation factor viia Biochemistry  2000 39:14457-14463  DOI:10.1021/bi0009486  PMID:11087398
    • Donate, F., Kelly, C. R., Ruf, W., Edgington, T. S. Dimerization of tissue factor supports solution-phase autoactivation of factor vii without influencing proteolytic activation of factor x Biochemistry  2000 39:11467-11476  DOI:10.1021/bi000986p  PMID:10985793
    • Baugh, R. J., Dickinson, C. D., Ruf, W., Krishnaswamy, S. Exosite interactions determine the affinity of factor x for the extrinsic xase complex Journal of Biological Chemistry  2000 275:28826-28833  DOI:10.1074/jbc.M005266200  PMID:10889208
    • Ott, I., Miyagi, Y., Miyazaki, K., Heeb, M. J., Mueller, B. M., Rao, L. V. M., Ruf, W. Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor Arteriosclerosis, Thrombosis, and Vascular Biology  2000 20:874-882  PMID:10712416
    • 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
    • Chang, Y. J., Hamaguchi, N., Chang, S. C., Ruf, W., Shen, M. C., Lin, S. W. Engineered recombinant factor vii q(217) variants with altered inhibitor specificities Biochemistry  1999 38:10940-10948  DOI:10.1021/bi990055h  PMID:10460149
    • Shobe, J., Dickinson, C. D., Edgington, T. S., Ruf, W. Macromolecular substrate affinity for the tissue factor-factor viia complex is independent of scissile bond docking Journal of Biological Chemistry  1999 274:24171-24175  DOI:10.1074/jbc.274.34.24171  PMID:10446191
    • Ruf, W., Mueller, B. M. Tissue factor signaling Thrombosis and Haemostasis  1999 82:175-182  PMID:10605702
    • Shobe, J., Dickinson, C. D., Ruf, W. Regulation of the catalytic function of coagulation factor viia by a conformational linkage of surface residue glu 154 to the active site Biochemistry  1999 38:2745-2751  DOI:10.1021/bi981951g  PMID:10052945
    • Ruf, W., Shobe, J., Rao, S. M., Dickinson, C. D., Olson, A., Edgington, T. S. Importance of factor VIIa Gla-domain residue Arg-36 for recognition of the macromolecular substrate factor X Gla-domain Biochemistry  1999 38:1957-1966  DOI:10.1021/bi982254r  PMID:10026279
    • Ruf, W., Dickinson, C. D. Allosteric regulation of the cofactor dependent serine protease coagulation factor viia Trends in Cardiovascular Medicine  1998 8:350-356  DOI:10.1016/s1050-1738(98)00031-0  PMID:14987549
    • Dickinson, C. D., Shobe, J., Ruf, W. Influence of cofactor binding and active site occupancy on the conformation of the macromolecular substrate exosite of factor viia Journal of Molecular Biology  1998 277:959-971  DOI:10.1006/jmbi.1998.1639  PMID:9545384
    • Mueller, B. M., Ruf, W. Requirement for binding of catalytically active factor viia in tissue factor-dependent experimental metastasis Journal of Clinical Investigation  1998 101:1372-1378  DOI:10.1172/jci930  PMID:9525979
    • Ott, I., Fischer, E. G., Miyagi, Y., Mueller, B. M., Ruf, W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280 Journal of Cell Biology  1998 140:1241-1253  DOI:10.1083/jcb.140.5.1241  PMID:9490735
    • Ruf, W. The interaction of activated factor vii with tissue factor: Insight into the mechanism of cofactor-mediated activation of activated factor vii Blood Coagulation & Fibrinolysis  1998 9:S73-S78  PMID:9819032
    • Huang, M. D., Syed, R., Stura, E. A., Stone, M. J., Stefanko, R. S., Ruf, W., Edgington, T. S., Wilson, I. A. The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex Journal of Molecular Biology  1998 275:873-894  DOI:10.1006/jmbi.1997.1512  PMID:9480775
    • Dickinson, C. D., Ruf, W. Active site modification of factor viia affects interactions of the protease domain with tissue factor Journal of Biological Chemistry  1997 272:19875-19879  DOI:10.1074/jbc.272.32.19875  PMID:9242651
    • Kelly, C. R., Dickinson, C. D., Ruf, W. Ca2+ binding to the first epidermal growth factor module of coagulation factor viia is important for cofactor interaction and proteolytic function Journal of Biological Chemistry  1997 272:17467-17472  DOI:10.1074/jbc.272.28.17467  PMID:9211891
    • Edgington, T. S., Dickinson, C. D., Ruf, W. The structural basis of function of the TF. VIIa complex in the cellular initiation of coagulation Thrombosis and Haemostasis  1997 78:401-405  PMID:9198187
    • Dittmar, S., Ruf, W., Edgington, T. S. Influence of mutations in tissue factor on the fine specificity of macromolecular substrate activation Biochemical Journal  1997 321:787-793  PMID:9032467  PMCID:PMC1218136
    • Dickinson, C. D., Kelly, C. R., Ruf, W. Identification of surface residues mediating tissue factor binding and catalytic function of the serine protease factor viia Proceedings of the National Academy of Sciences of the United States of America  1996 93:14379-14384  DOI:10.1073/pnas.93.25.14379  PMID:8962059
    • Nicholson, A. C., Nachman, R. L., Altieri, D. C., Summers, B. D., Ruf, W., Edgington, T. S., Hajjar, D. P. Effector cell protease receptor-1 is a vascular receptor for coagulation factor xa Journal of Biological Chemistry  1996 271:28407-28413  PMID:8910465
    • Stura, E. A., Ruf, W., Wilson, I. A. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor viia and a bpti-derived inhibitor Journal of Crystal Growth  1996 168:260-269  DOI:10.1016/0022-0248(96)00329-6
    • Sevinsky, J. R., Rao, L. V. M., Ruf, W. Ligand-induced protease receptor translocation into caveolae: A mechanism for regulating cell surface proteolysis of the tissue factor-dependent coagulation pathway Journal of Cell Biology  1996 133:293-304  DOI:10.1083/jcb.133.2.293  PMID:8609163
    • Kelly, C. R., Schullek, J. R., Ruf, W., Edgington, T. S. Tissue factor residue asp(44) regulates catalytic function of the bound proteinase factor vlla Biochemical Journal  1996 315:145-151  PMID:8670099  PMCID:PMC1217163
    • Speidel, C. M., Eisenberg, P. R., Ruf, W., Edgington, T. S., Abendschein, D. R. Tissue factor mediates prolonged procoagulant activity on the luminal surface of balloon-injured aortas in rabbits Circulation  1995 92:3323-3330  PMID:7586321
    • Stone, M. J., Ruf, W., Miles, D. J., Edgington, T. S., Wright, P. E. Recombinant soluble human tissue factor secreted by saccharomyces-cerevisiae and refolded from escherichia-coli inclusion-bodies - glycosylation of mutants, activity and physical characterization Biochemical Journal  1995 310:605-614  PMID:7654202  PMCID:PMC1135939
    • Rao, L. V. M., Ruf, W. Tissue factor residues lys(165) and lys(166) are essential for rapid formation of the quaternary complex of tissue-factor-center-dot-viia with xa-center-dot-tissue factor pathway inhibitor Biochemistry  1995 34:10867-10871  DOI:10.1021/bi00034a020  PMID:7662667
    • Martin, D. M. A., Boys, C. W. G., Ruf, W. Tissue factor - molecular recognition and cofactor function FASEB Journal  1995 9:852-859  PMID:7615155
    • Ruf, W., Kelly, C. R., Schullek, J. R., Martin, D. M. A., Polikarpov, I., Boys, C. W. G., Tuddenham, E. G. D., Edgington, T. S. Energetic contributions and topographical organization of ligand-binding residues of tissue factor Biochemistry  1995 34:6310-6315  DOI:10.1021/bi00019a008  PMID:7756258
    • Fischer, E. G., Ruf, W., Mueller, B. M. Tissue factor-initiated thrombin generation activates the signaling thrombin receptor on malignant-melanoma cells Cancer Research  1995 55:1629-1632  PMID:7712465
    • Ruf, W. Factor viia residue arg(290) is required for efficient activation of the macromolecular substrate factor-x Biochemistry  1994 33:11631-11636  DOI:10.1021/bi00204a026  PMID:7918377
    • Schullek, J. R., Ruf, W., Edgington, T. S. Key ligand interface residues in tissue factor contribute independently to factor viia binding Journal of Biological Chemistry  1994 269:19399-19403  PMID:8034706
    • Ruf, W., Edgington, T. S. Structural biology of tissue factor, the initiator of thrombogenesis in vivo FASEB Journal  1994 8:385-390  PMID:8168689
    • Ruf, W., Schullek, J. R., Stone, M. J., Edgington, T. S. Mutational mapping of functional residues in tissue factor - identification of factor-vii recognition determinants in both structural modules of the predicted cytokine receptor homology domain Biochemistry  1994 33:1565-1572  DOI:10.1021/bi00172a037  PMID:8312277
    • Ihnken, K., Speiser, W., Ruf, W., Thiel, W., Schlepper, M., Mullerberghaus, G. High pai activity with correlation to triglyceride and hdl cholesterol values in patients with coronary-artery disease with no difference in survivors of myocardial-infarction Annals of Hematology  1993 67:237-244  DOI:10.1007/bf01715054  PMID:8241347
    • Ruf, W., Rehemtulla, A., Edgington, T. S. Mutational analysis of receptor and cofactor function of tissue factor Methods in Enzymology  1993 222:209-224  PMID:8412795
    • Ruf, W., Rehemtulla, A., Edgington, T. S. Mutational analysis of receptor and cofactor function of tissue factor Proteolytic Enzymes in Coagulation, Fibrinolysis, and Complement Activation, Part A  1993 222:209-224  PMID:8412795
    • Mueller, B. M., Reisfeld, R. A., Edgington, T. S., Ruf, W. Expression of tissue factor by melanoma-cells promotes efficient hematogenous metastasis Proceedings of the National Academy of Sciences of the United States of America  1992 89:11832-11836  DOI:10.1073/pnas.89.24.11832  PMID:1465406
    • Ruf, W., Miles, D. J., Rehemtulla, A., Edgington, T. S. Tissue factor residues 157-167 are required for efficient proteolytic activation of factor-x and factor-vii Journal of Biological Chemistry  1992 267:22206-22210  PMID:1429572
    • Ruf, W., Stura, E. A., Lapolla, R. J., Syed, R., Edgington, T. S., Wilson, I. A. Purification, sequence and crystallization of an antitissue factor fab and its use for the crystallization of tissue factor Journal of Crystal Growth  1992 122:253-264  DOI:10.1016/0022-0248(92)90254-g
    • Edgington, T. S., Mackman, N., Fan, S. T., Ruf, W. Cellular immune and cytokine pathways resulting in tissue factor expression and relevance to septic shock Nouvelle Revue Francaise d Hematologie  1992 34:S15-S27  PMID:1364116
    • Ruf, W., Miles, D. J., Rehemtulla, A., Edgington, T. S. Cofactor residues lysine-165 and lysine-166 are critical for protein substrate recognition by the tissue factor-factor-viia protease complex Journal of Biological Chemistry  1992 267:6375-6381  PMID:1372908
    • Rehemtulla, A., Ruf, W., Miles, D. J., Edgington, T. S. The third Trp-Lys-Ser (WKS) tripeptide motif in tissue factor is associated with a function site Biochemical Journal  1992 282:737-740  PMID:1554354  PMCID:PMC1130849
    • Ruf, W., Edgington, T. S. An antitissue factor monoclonal-antibody which inhibits tf-viia complex is a potent anticoagulant in plasma Thrombosis and Haemostasis  1991 66:529-533  PMID:1803616
    • Ruf, W., Edgington, T. S. Two sites in the tissue factor extracellular domain mediate the recognition of the ligand factor VIIa Proceedings of the National Academy of Sciences of the United States of America  1991 88:8430-8434  DOI:10.1073/pnas.88.19.8430  PMID:1924302  PMCID:PMC52522
    • Ruf, W., Rehemtulla, A., Edgington, T. S. Antibody mapping of tissue factor implicates 2 different exon-encoded regions in function Biochemical Journal  1991 278:729-733  PMID:1716883  PMCID:PMC1151407
    • Ruf, W., Kalnik, M. W., Lundhansen, T., Edgington, T. S. Characterization of factor-vii association with tissue factor in solution - high and low affinity calcium-binding sites in factor-vii contribute to functionally distinct interactions Journal of Biological Chemistry  1991 266:15719-15725  PMID:1874730
    • Edgington, T. S., Mackman, N., Brand, K., Ruf, W. The structural biology of expression and function of tissue factor Thrombosis and Haemostasis  1991 66:67-79  PMID:1833852
    • Rehemtulla, A., Ruf, W., Edgington, T. S. The integrity of the cysteine-186-cysteine-209 bond of the 2nd disulfide loop of tissue factor is required for binding of factor-vii Journal of Biological Chemistry  1991 266:10294-10299  PMID:2037582
    • Taylor, F. B., Chang, A., Ruf, W., Morrissey, J. H., Hinshaw, L., Catlett, R., Blick, K., Edgington, T. S. Lethal escherichia-coli septic shock is prevented by blocking tissue factor with monoclonal-antibody Circulatory Shock  1991 33:127-134  PMID:2044206
    • Ruf, W., Rehemtulla, A., Edgington, T. S. Phospholipid-independent and phospholipid-dependent interactions required for tissue factor receptor and cofactor function Journal of Biological Chemistry  1991 266:2158-2166  PMID:1989976
    • Drake, T. A., Ruf, W., Morrissey, J. H., Edgington, T. S. Functional tissue factor is entirely cell-surface expressed on lipopolysaccharide-stimulated human-blood monocytes and a constitutively tissue factor producing neoplastic cell-line Journal of Cell Biology  1989 109:389-395  DOI:10.1083/jcb.109.1.389  PMID:2663880
    • Ruf, W., Bender, A., Lane, D. A., Preissner, K. T., Selmayr, E., Mullerberghaus, G. Thrombin-induced fibrinopeptide-b release from normal and variant fibrinogens - influence of inhibitors of fibrin polymerization Biochimica et Biophysica Acta  1988 965:169-175  DOI:10.1016/0304-4165(88)90053-0  PMID:3365451
  • chapter

    • Gur-Cohen, S., Kollet, O., Graf, C., Esmon, C. T., Ruf, W., Lapidot, T. Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling Hematopoietic Stem Cells Ix. 65-81. 2016  DOI:10.1111/nyas.13013

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Research

research overview

  • The laboratory's interest are studies in vascular biology and immunology employing cell and molecular biology and transgenic animal technology. The TF-initiated coagulation pathway has remained a major focus of ongoing research, because of its critical role in cell signaling that drives systemic inflammation, metastasis and angiogenesis. Building on a comprehensive elucidation of the structural biology of TF and its protease ligand VIIa, we developed biochemical models of how cell signaling and initiation of coagulation are closely interrelated. We have defined relevant TF-driven signaling pathways through protease activated receptors (PARs) and have identified the underlying signaling mechanism of the anti-apoptotic and vascular protective effects of the anticoagulant activated protein C. The laboratory is focused on the basic cell biology of TF and how TF regulates the signaling of integrins and PARs. We are utilizing a number of newly generated animal models with altered signaling properties in the TF coagulation pathway. These models are under investigation to define the signaling specificity of the TF coagulation pathway in angiogenesis, oncogenic tranformation and inflammation.
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Background

education and training

  • Ph.D., Max Planck Society for the Advancement of Science , Clinical Research Unit for Blood Coagulation and Thrombosis 1986
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Contact

full name

  • Wolfram Ruf

geographic location

  • Scripps California 

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