Wolfram Ruf, MD - Scripps Research

Research Focus

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.

Education

Professional Experience

Awards & Professional Activities

Select Publications

Riewald, Matthias; Ruf, Wolfram 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.
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Riewald, Matthias; Petrovan, R. J.; Donner, A.; Mueller, B. M.; Ruf, Wolfram Activation of endothelial cell protease activated receptor 1 by the protein c pathway. Science 2002, 296, 1880-1882.
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Belting, M.; Dorrell, Michael I.; Sandgren, S.; Aguilar, E.; Ahamed, J.; Dorfleutner, A.; Carmeliet, P.; Mueller, B. M.; Friedlander, Martin; Ruf, Wolfram Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nature Medicine 2004, 10, 502-509.
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Ahamed, J.; Versteeg, H. H.; Kerver, M.; Chen, V. M.; Mueller, B. M.; Hogg, P. J.; Ruf, Wolfram Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proceedings of the National Academy of Sciences of the United States of America 2006, 103, 13932-13937.
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Versteeg, H. H.; Schaffner, F.; Kerver, M.; Petersen, H. H.; Ahamed, J.; Felding-Habermann, Brunhilde; Takada, Y.; Mueller, B. M.; Ruf, Wolfram Inhibition of tissue factor signaling suppresses tumor growth. Blood 2008, 111, 190-199.
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Schaffner, F.; Versteeg, H. H.; Schillert, A.; Yokota, N.; Petersen, L. C.; Mueller, B. M.; Ruf, Wolfram Cooperation of tissue factor cytoplasmic domain and par2 signaling in breast cancer development. Blood 2010, 116, 6106-6113.
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