The laboratory's interests are studies in vascular biology and immunology employing cell, 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 transformation and inflammation.
1984-1986 Doctoral Fellowship, Clinical Research Unit for Blood Coagulation and Thrombosis of the Max-Planck Gesellschaft.
1987-1988 Research Associate, Clinical Research Unit for Blood Coagulation and Thrombosis of the Max-Planck Gesellschaft.
1988-1990 Exchange Visitor, Dept. of Immunology, Scripps Clinic, La Jolla, CA.
1990-1992 Senior Research Associate, The Scripps Research Institute, La Jolla, CA.
1992-1996 Assistant Professor, The Scripps Research Institute, La Jolla, CA.
1996-2005 Associate Professor (tenured 2001), The Scripps Research Institute, La Jolla, CA.
2005-present Professor, The Scripps Research Institute, La Jolla, CA.
2007-present Margaret Thatcher Professor of Biological Chemistry, Thrombosis Research Institute, London, U.K. (external affiliation)
1988 Otto Hahn Medal Max-Planck-Gesellschaft, Germany
1996 Established Investigator Award of the American Heart Association
1999 Membership (elected) American Society for Clinical Investigation
2005 Investigator Recognition Award ISTH
2005 Special Recognition Award ATVB Council, American Heart Association
2007 Sol Sherry Distinguished Lecturer in Thrombosis, ATVB Council, American Heart Association
2007 – present Hemostasis & Thrombosis NIH Study Section
Riewald, M., Ruf, W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor. Proc. Natl. Acad. Sci. USA. 98:7742-7, 2001.
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 296:1880-1882, 2002.
Belting, M., Dorrell, M.I., Sandgren, S., Aguilar, E., Ahamed, J., Dorfleutner, A., Carmeliet, P., Mueller, B.M., Friedlander, M., Ruf,W. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nature Med. 10:502-9, 2004.
Dorfleutner, A., Hintermann, E., Tarui, T., Takada, Y., Ruf, W. Crosstalk of integrin α3β1 and tissue factor in cell migration. Mol. Biol. Cell, 15:4416-4425, 2004.
Ahamed, A., Versteeg, H.H., Kerver, M., Chen, V.M., Mueller, B.M., Hogg, P.J., Ruf, W. Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc. Natl. Acad. Sci. USA, 103:13932-13937, 2006.
Versteeg, H.H., Schaffner, F., Kerver, M., Petersen, H.H., Ahamed, J., Felding-Habermann, B., Takada, Y., Mueller, B., Ruf, W. Inhibition of tissue factor signaling suppresses tumor growth. Blood 111:190-199, 2008. PMCID: PMC2200804.
Schaffner, F., Versteeg, H.H., Schillert, A., Yokota, N., Petersen, L.C., Bueller, B.M., Ruf, W. Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development. Blood, 116(26):6106-13, 2010.
Disse, J., Petersen, H.H., Larsen, K.S., Persson, E., Esmon, N., Esmon, C.T., Teyton, L., Petersen, L.C., Ruf, W. The endothelial protein C receptor supports tissue factor ternary coagulation initiation complex signaling through protease-activated receptors. J Biol Chem, 286(7):5756-67, 2011.
Furlan-Freguia, C., Marchese, P., Gruber, A., Ruggeri, Z.M., Ruf, W. P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin Invest, 121(7):2932-44, 2011.