Visual Universitätsmedizin Mainz

Alexander von Humboldt-Professorship

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.

Research Interests

  • 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 Stiftung
  • BMBF 'Clusters4Future' - curATime (Cluster für Atherothrombose und Individualisierte Medizin)
  • Horizon 2020 - Marie Skłodowska-Curie Innovative Training Network (TICARDIO Research Consortium)
  • DFG (CRC 1292: TP02 and TP10)
  • DFG TransRegio 156
  • DZHK
  • ReALity Innovation Fund (Forschungsinitiative des Landes Rheinland-Pfalz)
  • BIS Cardio Consortium
  • Iconics Therapeutics, Inc.

Team

Ruf, MD
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

06131 17-8222
06131 17-3456

Platzhalterbild
Giusy Carlino
Position: Technical Assistant

06131 17-8028

PhD Dörr
Angela Dörr, PhD
Position: Post Doc, Virchow Fellow

06131 17-8028

Platzhalterbild
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)

Grunz
Kristin Grunz
Position: PhD student

06131 17-8021
06131 17-8047

Kaur
Dilraj Kaur
Position: PhD student

06131 17-8018

Lahiri
Trisha Lahiri
Position: PhD student

Nguyen
Thanh Son Nguyen
Position: PhD student

06131 17-8021
06131 17-8047

Dr. Nourse
Cathrin Nourse, Dr.
Position: Scientific Coordination CTH

06131 17-8056

Platzhalterbild
Sven Pagel
Position: PhD student

06131 17-8021
06131 17-8047

Pott
Jennifer Pott
Position: PhD student

06131/17-8021
06131/17-8047

Platzhalterbild
Sabine Reyda
Position: Research Coordinator

06131 17-8048

Rodrigues (geb. Santos)
Carina Rodrigues (geb. Santos)
Position: PhD student

06131 17-8021
06131 17-8047

Platzhalterbild
Madhusudhan Thati, PhD
Position: Post Doc

06131 17-8014

Platzhalterbild
Petra Wilgenbus
Position: Technician

06131 17-8028

Witzler
Claudius Witzler
Position: PhD student

06131 17-8018

Wolz
Romina Wolz
Position: PhD student

06131 17-8018

We are looking forward to applications from highly motivated scientists.
Find out more (Pdf-file, 64,2 KB).

Selected publications

  • Müller-Calleja N, Hollerbach A, Royce J, Ritter S, Pedrosa D, Madhusudhan T, Teifel S, Meineck M, Häuser F, Canisius A, Nguyen TS, Braun J, Bruns K, Etzold A, Zechner U, Strand S, Radsak M, Strand D, Gu JM, Weinmann-Menke J, Esmon CT, Teyton L, Lackner KJ*, Ruf W*. Lipid presentation by the protein C receptor links coagulation with autoimmunity. Science (2021) 371:eabc0956. Link
  • Saffarzadeh M, Grunz K, Nguyen TS, Lee YK, Kitano M, Danckwardt S, Santos CD, Weiler H, Reyda S, Ruf W. Macrophage Protease-Activated Receptor 2 Regulates Fetal Liver Erythropoiesis in Mice. Blood Adv. (2020). 4:5810-5824
  • Graf C, Wilgenbus P, Pagel S, Pott J, Marini F, Reyda S, Kitano M, Macher-Göppinger S, Weiler H, Ruf W. Myeloid cell-synthesized coagulation factor X dampens antitumor immunity.  Sci Immunol (2019) 20;4(39). pii: eaaw8405.
  • 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. Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis. Blood (2019). 3;134(14):1119-1131.
  • 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.

Reviews

  • Mast AE, Ruf W. Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy. J Thromb Haemost. 2022 Jun;20(6):1290-1300.
  • Ruf W. Roles of factor Xa beyond coagulation. J Thromb Thrombolysis. 2021 Aug;52(2):391-396.
  • Ruf W, Graf C. Coagulation signaling and cancer immunotherapy. Thromb Res. 2020 Jul;191 Suppl 1:S106-S111.
  • 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.

Editorials, Comments and other articles

  • Subramaniam S, Ruf W, Bosmann M. Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019. Br J Pharmacol. 2022 May;179(10):2086-2099.
  • Ruggeri ZM, Ruf W. Is VITT really a HIT. Nat Immunol. 2021 Nov;22(11):1352-1353.
  • Ruf W. TRIF turns the switch for DIC in sepsis. Blood. 2020 Apr 2;135(14):1073-1074.
  • Ruf W. Translational Research in Thrombosis and Haemostasis. Hamostaseologie. 2019 Jun;39(2):115-116.
  • Kiouptsi K, Ruf W, Reinhardt C. Microbiota-Derived Trimethylamine. Circ Res. 2018 Oct 26;123(10):1112-1114.
  • Ruf W, Preissner KT. State of the Art 2017. J Thromb Haemost. 2017 Jul;15(7):1239.
July 2022

curATime funded by the Federal Ministry of Education and Research (BMBF). Press Release

November 2021

Collaborative Research Center (CRC) 1292 'Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections' started 2nd funding round. Press Release

March 2021

Mechanismus of the autoimmune disease APS described by CTH researchers. Press Release and publication

February 2013


Professor Wolfram Ruf, MD
receives Alexander von Humboldt Professorship - awarded by the Federal Minister of Research Prof. Wanka in Berlin (Media AvH-Foundation)