Professor Wolfram Ruf, MD
Professorship for Cell Signaling Pathways of the Hemostatic System
The hemostatic system is comprised of the coagulation and fibrinolytic protease cascades, platelets, and cellular receptors on immune and vascular cells. The hemostatic response to infection and tissue injury supports inflammatory and immune reactions, but the coagulation pathways are increasingly recognized as major players and molecular targets for interventional therapy in cancer progression, atherosclerosis, chronic inflammatory disorders, and the metabolic syndrome associated with obesity. We are interested in the crosstalk of coagulation and inflammation and study contributions of inflammatory processes to the initiation of coagulation by tissue factor (TF). Our research also broadly addresses open question related to the roles of TF and coagulation protease signaling networks in the integration and modulation of inflammatory stimuli in immune cells. We are interested in the control of macrophage phenotypes by coagulation proteases and their receptors in chronic inflammation and use novel genetic mouse models that selectively delete or alter signaling specificity of components of the hemostatic system in innate immune cell populations. This genetic platform is employed in combination with transcriptional and proteomics approaches for generating fundamentally novel insights into cellular and molecular connections between coagulation and inflammation. We are interested in translational research that deciphers molecular mechanisms of diseases of the cardiovascular system and evaluates clinically relevant interventional proof-of-principle molecular probes in disease models.
- Molecular mechanisms of prothrombotic activation of TF
- Coagulation protease signaling in myelo-monocytic cells
- Protease activated receptor (PAR) signaling specificity in inflammation
- Crosstalk of the hemostatic system with tumor progression and angiogenesis
Third party funding
- Alexander von Humboldt Foundation
- BMBF (CTH TRP X6, X7)
- SFB 1292, TP02 & TP10
- Boehringer Ingelheim Foundation
Professor Wolfram Ruf, MD
Position: Scientific Director CTH, Alexander von Humboldt-Professorship "Experimental Hemostasiology", Deputy Speaker of CTH, Deputy Speaker of CTVB, Principal Investigator DZHK
Angela Dörr, PhD
Position: Post Doc, Virchow Fellow
PD Claudine Graf, MD PhD
Position: Junior group leader
Physician UCT Mainz
Qualifications: Specialist in Internal Medicine, Hematology and Oncology, Additional qualification: Palliative Care, Hemostaseology
06131 17-8014 (Office) bzw. -8027 (Lab)
We are looking forward to applications from highly motivated scientists.
Find out more (Pdf-file, 64,2 KB).
Relevant selected publications
- Myeloid cell-synthesized coagulation factor X dampens antitumor immunity. Graf C, Wilgenbus P, Pagel S, Pott J, Marini F, Reyda S, Kitano M, Macher-Göppinger S, Weiler H, Ruf W. Sci Immunol. 2019 Sep 20;4(39). pii: eaaw8405. doi: 10.1126/sciimmunol.aaw8405.
- Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis. Müller-Calleja N, Hollerbach A, Ritter S, Pedrosa DG, Strand D, Graf C, Reinhardt C, Strand S, Poncelet P, Griffin JH, Lackner KJ, Ruf W. Blood. 2019. pii: blood.2019001530. [Epub ahead of print]
- Ebert J, Wilgenbus P, Teiber JF, Jurk K, Schwierczek K, Döhrmann M, Xia N, Li H, Spiecker L, Ruf W, Horke S. Paraoxonase-2 regulates coagulation activation through endothelial tissue factor. Blood 2018;131(19):2161-2172.
- Müller-Calleja N, Ritter S, Hollerbach A, Falter T, Lackner KJ, Ruf W. Complement C5 but not C3 is expendable for tissue factor activation by cofactor-independent antiphospholipid antibodies. Blood Adv 2018;2(9):979-986.
- Rothmeier AS, Liu E, Chakrabarty S, Disse J, Mueller BM, Ostergaard H, Ruf W. Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling. Blood 2018;131(6):674-685.
- Kamikubo Y, Mendolicchio GL, Zampolli A, Marchese P, Rothmeier AS, Orje JN, Gale AJ, Krishnaswamy S, Gruber A, Ostergaard H, Petersen LC, Ruf W, Ruggeri ZM (2017) Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex. Blood 130: 1661-1670
- Rothmeier AS, Marchese P, Langer F, Kamikubo Y, Schaffner F, Cantor J, Ginsberg MH, Ruggeri ZM, Ruf W (2017) Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking. Arteriosclerosis, thrombosis, and vascular biology 37: 1323-1331
- Kossmann S, Lagrange J, Jäckel S, Jurk K, Ehlken M, Schönfelder 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, Renné T, Ruf W, Münzel T, Wenzel P (2017) Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med 9
- Subramaniam S, Jurk K, Hobohm L, Jäckel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C, Ruf W (2017) Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood 129: 2291-2302
- Cohen SG, Itkin T, Chakrabarty S, Graf C, Kollet O, Ludin A, Golan K, Kalinkovich A, Ledergor G, Wong E, Niemeyer E, Porat Z, Erez A, Sagi I, Esmon CT, Ruf W, Lapidot T. PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells. Nature medicine. 21:1307-1317. 2015. (WR & TL share senior authorship.)
- Rothmeier AS, Marchese P, Petrich BG, Furlan-Freguia C, Ginsberg MH, Ruggeri ZM, Ruf W. Caspase-1-mediated pathway promotes generation of thromboinflammatory microparticles. The Journal of clinical investigation. 125:1471-1484. 2015.
- Liang HP, Kerschen EJ, Hernandez I, Basu S, Zogg M, Botros F, Jia S, Hessner MJ, Griffin JH, Ruf W, Weiler H. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice. Blood. 125:2845-2854. 2015.
- Schaffner F, Yokota N, Carneiro-Lobo T, Kitano M, Schaffer M, Anderson GM, Mueller BM, Esmon CT, Ruf W. Endothelial protein C receptor function in murine and human breast cancer development. PloS one. 8:e61071, 2013.
- Furlan Freguia C, Marchese P, Gruber A, Ruggeri ZM, Ruf W. P2X7 signaling triggers tissue factor-dependent thrombosis in mice. J. Clin. Invest. 121(7):2932-2944, 2011.
- Badeanlou L, Furlan-Freguia C, Yang G, Ruf W., Samad, F. Tissue factor-PAR2 signaling promotes diet-induced obesity and adipose tissue macrophage inflammation. Nat. Med. 17: 1490-7, 2011.
- Schaffner F, Versteeg HH, Schillert A, Yokota N, Petersen LC, Mueller BM, Ruf W. Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development. Blood. 116(26):6106-13, 2010.
- Versteeg HH, Schaffner F, Kerver M, Petersen HH, Ahamed J, Felding-Habermann B, Takada Y, Mueller B, Ruf W. Inhibition of tissue factor signaling suppresses tumor growth. Blood. 111:190-199, 2008.
- Ahamed A, Versteeg HH, Kerver M, Chen VM, Mueller BM, Hogg PJ, Ruf W. Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc. Natl. Acad. Sci. USA 103:13932-13937, 2006.
- Belting M, Dorrell MI, Sandgren S, Aguilar E, Ahamed J, Dorfleutner A, Carmeliet P, Mueller BM, Friedlander M, Ruf W. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nature Med. 10:502-9, 2004.
- Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science. 296:1880-1882, 2002.
- Madhusudhan T, Ruf W. Coagulation Signalling and Metabolic Disorders: Lessons Learned from Animal Models. Hamostaseologie. 2019. 39(2):164-172. doi: 10.1055/s-0039-1688800.
- Ruf W. ISTH 2017 Berlin revisited. Res Pract Thromb Haemost 2018;2(1):17-18.
- Zelaya H, Rothmeier AS, Ruf W. Tissue factor at the crossroad of coagulation and cell signaling. J Thromb Haemost 2018;16(10):1941-1952.
- Nguyen TS, Lapidot T, Ruf W. Extravascular coagulation in hematopoietic stem and progenitor cell regulation. Blood 2018.
- Ruf W. Proteases, Protease-Activated Receptors, and Atherosclerosis. Arterioscler Thromb Vasc Biol 2018;38(6):1252-1254.
- Langer F, Ruf W. Synergies of phosphatidylserine and protein disulfide isomerase in tissue factor activation. Thromb Haemost. 111, 2014.
- Rothmeier A, Ruf W. Protease-activated receptor 2 signaling in inflammation. Seminars in Immunopathology. 34:133-49, 2012.
- Ruf W. Chapter 44: Coagulation-Independent Signaling of the Extrinsic Coagulation Pathway. In: Marder, V., Aird, W. C., Bennett, J., Schulman, S., White, G. CC. (Eds.): Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 6e. Lippincott Williams & Wilkins. 579-584, 2012.
- Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis. J. Thromb. Haemost. 9 S1:306-15, 2011.