Center for Thrombosis and Hemostasis (CTH)

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
  • DFG TRR 355
  • 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

  • Fleischer MI, Röhrig N, Raker VK, Springer J, Becker D, Ritz S, Bros M, Stege H, Haist M, Grabbe S, Haub J, Becker C, Reyda S, Disse J, Schmidt T, Mahnke K, Weiler H, Ruf W*, Steinbrink K*. Protease- and cell type-specific activation of protease-activated receptor 2 in cutaneous inflammation. J Thromb Haemost. 2022 Dec;20(12):2823-2836
  • Bochenek ML, Gogiraju R, Großmann S, Krug J, Orth J, Reyda S, Georgiadis GS, Spronk HM, Konstantinides S, Münzel T, Griffin JH, Wild P, Espinola-Klein C, Ruf W*, Schäfer K. EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia. JCI Insight. 2022 Jul 22;7(14):e157701
  • Hollerbach A, Müller-Calleja N, Pedrosa D, Canisius A, Sprinzl MF, Falter T, Rossmann H, Bodenstein M, Werner C, Sagoschen I, Münzel T, Schreiner O, Sivanathan V, Reuter M, Niermann J, Galle PR, Teyton L, Ruf W*, Lackner KJ*. Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19. J Thromb Haemost. 2021 Sep;19(9):2335-2347
  • 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 Mar 12;371(6534):eabc0956
  • Saffarzadeh M, Grunz K, Nguyen TS, Lee YK, Kitano M, Danckwardt S, Rodrigues CDS, Weiler H, Reyda S, Ruf W. Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice. Blood Adv. 2020 Nov 24;4(22):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 Sep 20;4(39):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 Oct 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 May 10;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, Østergaard H, Petersen LC, Ruf W, Ruggeri ZM. Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex. Blood. 2017 Oct 5;130(14):1661-1670
  • Rothmeier AS, Marchese P, Langer F, Kamikubo Y, Schaffner F, Cantor J, Ginsberg MH, Ruggeri ZM, Ruf W. Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking. Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):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. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med. 2017 Feb 1;9(375):eaah4923
  • Subramaniam S, Jurk K, Hobohm L, Jäckel 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 Apr 20;129(16):2291-2302.
  • Gur-Cohen S, 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. Nat Med. 2015 Nov;21(11):1307-17
  • Rothmeier AS, Marchese P, Petrich BG, Furlan-Freguia C, Ginsberg MH, Ruggeri ZM, Ruf W. Caspase-1-mediated pathway promotes generation of thromboinflammatory microparticles. J Clin Invest. 2015 Apr;125(4):1471-84.
  • 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. 2015 Apr 30;125(18):2845-54.
  • 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. 2013 Apr 9;8(4):e61071
  • Furlan-Freguia C, Marchese P, Gruber A, Ruggeri ZM, Ruf W. P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin Invest. 2011 Jul;121(7):2932-44
  • Badeanlou L, Furlan-Freguia C, Yang G, Ruf W, Samad F. Tissue factor-protease-activated receptor 2 signaling promotes diet-induced obesity and adipose inflammation. Nat Med. 2011 Oct 23;17(11):1490-7.
  • 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. 2010 Dec 23;116(26):6106-13.
  • Versteeg HH, Schaffner F, Kerver M, Petersen HH, Ahamed J, Felding-Habermann B, Takada Y, Mueller BM, Ruf W. Inhibition of tissue factor signaling suppresses tumor growth. Blood. 2008 Jan 1;111(1):190-9
  • Ahamed J, 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 U S A. 2006 Sep 19;103(38):13932-7
  • 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. Nat Med. 2004 May;10(5):502-9. doi: 10.1038/nm1037
  • Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science. 2002 Jun 7;296(5574):1880-2

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

  • Koizume S, Kobayashi S, Ruf W, Miyagi Y. Authors' reply to the Letter to the Editor: Tissue factor and its procoagulant activity on cancer-associated thromboembolism in pancreatic cancer. Cancer Sci. 2022 May;113(5):1888-1890
  • 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.
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Last Update: Feb 06, 2023
Information about the CTH
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)