Tilman Hackeng


Prof. Tilman Hackeng studied biochemistry at the University of Utrecht and obtained his PhD at the same University in 1993 on protein C/protein S anticoagulant mechanisms. Shortly after, he left for The Scripps Research Institute, La Jolla, CA, USA, were he worked on translational chemistry in the laboratories of Molecular and Experimental Medicine and Cell Biology.

In 1998, he returned to the Netherlands as a Research Fellow of the Royal Netherlands Academy of Arts and Sciences (KNAW) at the Department of Biochemistry of the University Maastricht. He is past president of the Netherlands Society on Thrombosis and Hemostasis (NVTH), and elected member of the Royal Holland Society of Sciences and Humanities (KHMW). In addition, he is chair of the Scientific Advisory Board of the Netherlands Thrombosis Foundation, acts as reviewer for major journals in the Thrombosis & Haemostasis and Chemistry fields and serves on grant reviewing boards of national and international granting agencies. Currently he is chairman of the Department of Biochemistry of the University Maastricht and Scientific Director of CARIM. He is co-founder of ACS Biomarker BV and Coagulation Profile BV.

His research on chemistry and structure function relationships of blood coagulation proteins explores the involvement of blood coagulation proteins in developing cardiovascular disease. With an emphasis on anticoagulant regulatory pathways, a multidisciplinary approach is used in unraveling functional properties of proteins involved in the regulation of thrombin formation. Functional impairments of coagulation proteins can lead to development of venous and arterial thrombosis, and a fundamental understanding of inter-protein and protein-vessel wall interactions is a prerequisite for understanding how anticoagulant proteins work in preventing thrombosis. A broad technology platform is applied to this programme, from automated thrombin generation, total chemical synthesis of proteins, to NMR protein structural analysis and development of clinical assays. Additional research programmes performed in his laboratory for total chemical protein synthesis comprise several research lines and collaborations in the field of haemostasis and thrombosis, cancer, targeted molecular imaging and synthetic vaccines. Multimodal and multivalent constructs are applied as molecular imaging agents in vitro and in vivo for the targeting and MRI, SPECT, and PET imaging of thrombosis, atherosclerosis and angiogenesis and further developed within Maastricht Imaging Valley under the evolving discipline of translational cardiovascular chemistry.

Department of Biochemistry
Universiteitsingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht
Room number: 4.366
T: +31 (0)43 388 1674/1766

  • 2014
    • Peraramelli, S., Thomassen, S., Heinzmann, A., Rosing, J., Hackeng, T. M., Hartmann, R., Scheiflinger, F., & Dockal, M. (2014). Inhibition of tissue factor: factor VIIa-catalyzed factor IX and factor X activation by TFPI and TFPI constructs. Journal of Thrombosis and Haemostasis, 12(11), 1826-1837. https://doi.org/10.1111/jth.12713
    • Kapsokalyvas, D., Schiffers, P. M. H., Maij, N., Suylen, D. P., Hackeng, T. M., van Zandvoort, M. A. M. J., & De Mey, J. G. R. (2014). Imaging evidence for endothelin ETA/ETB receptor heterodimers in isolated rat mesenteric resistance arteries. Life Sciences, 111(1-2), 36-41. https://doi.org/10.1016/j.lfs.2014.07.007
    • Schmitt, M. M. N., Fraemohs, L., Hackeng, T. M., Weber, C., & Koenen, R. R. (2014). Atherogenic mononuclear cell recruitment is facilitated by oxidized lipoprotein-induced endothelial junctional adhesion molecule-A redistribution. Atherosclerosis, 234(2), 254-264. https://doi.org/10.1016/j.atherosclerosis.2014.03.014
    • Projahn, D., Simsekyilmaz, S., Singh, S., Kanzler, I., Kramp, B. K., Langer, M., Burlacu, A., Bernhagen, J., Klee, D., Zernecke, A., Hackeng, T. M., Groll, J., Weber, C., Liehn, E. A., & Koenen, R. R. (2014). Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction. Journal of Cellular and Molecular Medicine, 18(5), 790-800. https://doi.org/10.1111/jcmm.12225
    • Chatzigeorgioua, A., Seijkens, T., Zarzycka, B., Engel, D., Poggi, M., van den Berg, S., van den Berg, S., Soehnlein, O., Winkels, H., Beckers, L., Lievens, D., Driessen, A., Kusters, P., Biessen, E., Garcia-Martin, R., Ameln, A. K., Gijbels, M., Noelle, R., Boon, L., ... Lutgens, E. (2014). Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. Proceedings of the National Academy of Sciences of the United States of America, 111(7), 2686-2691. https://doi.org/10.1073/pnas.1400419111
    • Schmitt, M. M. N., Megens, R. T. A., Zernecke, A., Bidzhekov, K., van den Akker, N. M., Rademakers, T., van Zandvoort, M. A., Hackeng, T. M., Koenen, R. R., & Weber, C. (2014). Endothelial Junctional Adhesion Molecule-A Guides Monocytes Into Flow-Dependent Predilection Sites of Atherosclerosis. Circulation, 129(1), 66-+. https://doi.org/10.1161/CIRCULATIONAHA.113.004149
  • 2013
    • Agten, S. M., Suylen, D., Ippel, H., Kokozidou, M., Tans, G., van de Vijver, P., Koenen, R. R., & Hackeng, T. M. (2013). Chemoselective Oxime Reactions in Proteins and Peptides by Using an Optimized Oxime Strategy: The Demise of Levulinic Acid. Chembiochem, 14(18), 2431-2434. https://doi.org/10.1002/cbic.201300598
    • Nuzzo, F., Radu, C., Baralle, M., Spiezia, L., Hackeng, T. M., Simioni, P., & Castoldi, E. (2013). Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation. Blood, 122(23), 3825-3831. https://doi.org/10.1182/blood-2013-04-499657
    • Heeb, M. J., Mesters, R. M., Fernandez, J. A., Hackeng, T. M., Nakasone, R. K., & Griffin, J. H. (2013). Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation. Thrombosis and Haemostasis, 110(2), 275-282. https://doi.org/10.1160/TH12-12-0953
    • Dijkgraaf, I., Van de Vijver, P., Dirksen, A., & Hackeng, T. M. (2013). Synthesis and application of cNGR-containing imaging agents for detection of angiogenesis. Bioorganic & Medicinal Chemistry, 21(12), 3555-3564. https://doi.org/10.1016/j.bmc.2013.04.002
    • Winckers, K., ten Cate, H., & Hackeng, T. M. (2013). The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis. Blood Reviews, 27(3), 119-132. https://doi.org/10.1016/j.blre.2013.03.001
    • Peraramelli, S., Thomassen, S., Heinzmann, A., Rosing, J., Hackeng, T. M., Hartmann, R., Scheiflinger, F., & Dockal, M. (2013). Direct inhibition of factor VIIa by TFPI and TFPI constructs. Journal of Thrombosis and Haemostasis, 11(4), 704-714. https://doi.org/10.1111/jth.12152
    • Wantha, S., Alard, J-E., Megens, R. T. A., van der Does, A. M., Doering, Y., Drechsler, M., Pham, C. T. N., Wang, M-W., Wang, J-M., Gallo, R. L., von Hundelshausen, P., Lindbom, L., Hackeng, T., Weber, C., & Soehnlein, O. (2013). Neutrophil-Derived Cathelicidin Promotes Adhesion of Classical Monocytes. Circulation Research, 112(5), 792-801. https://doi.org/10.1161/CIRCRESAHA.112.300666
    • Kumar, N., Ippel, H., Weber, C., Hackeng, T., & Mayo, K. H. (2013). Protein lysine-N zeta alkylation and O-phosphorylation mediated by DTT-generated reactive oxygen species. Protein Science, 22(3), 327-346. https://doi.org/10.1002/pro.2214
    • Borissoff, J. I., Otten, J. J. T., Heeneman, S., Leenders, P., van Oerle, R., Soehnlein, O., Loubele, S. T. B. G., Hamulyak, K., Hackeng, T. M., Daemen, M. J. A. P., Degen, J. L., Weiler, H., Esmon, C. T., van Ryn, J., Biessen, E. A. L., Spronk, H. M. H., & ten Cate, H. (2013). Genetic and Pharmacological Modifications of Thrombin Formation in Apolipoprotein E-deficient Mice Determine Atherosclerosis Severity and Atherothrombosis Onset in a Neutrophil-Dependent Manner. PLOS ONE, 8(2), [e55784]. https://doi.org/10.1371/journal.pone.0055784
    • Rademakers, T., Douma, K., Hackeng, T. M., Post, M. J., Sluimer, J. C., Daemen, M. J. A. P., Biessen, E. A. L., Heeneman, S., & van Zandvoort, M. A. M. J. (2013). Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E-Deficient Mice Exhibit Proatherogenic Functional Features In Vivo. Arteriosclerosis Thrombosis and Vascular Biology, 33(2), 249-+. https://doi.org/10.1161/ATVBAHA.112.300087
    • Wolters, M., Mohades, S. G., Hackeng, T. M., Post, M. J., Kooi, M. E., & Backes, W. H. (2013). Clinical perspectives of hybrid proton-fluorine magnetic resonance imaging and spectroscopy.Investigative Radiology, 48(5), 341-350. https://doi.org/10.1097/RLI.0b013e318277528c
    • Wolters, M., van Hoof, R. H., Wagenaar, A., Douma, K., van Zandvoort, M. A., Hackeng, T. M., Post, M. J., Backes, W. H., & Kooi, M. E. (2013). MRI artifacts in the ferric chloride thrombus animal model: an alternative solution: preventing MRI artifacts after thrombus induction with a non-ferromagnetic Lewis acid. Journal of Thrombosis and Haemostasis, 11(9), 1766-1769. https://doi.org/10.1111/jth.12340
  • 2012
    • Van de Vijver, P., Schmitt, M., Suylen, D., Scheer, L., Thomassen, M. C. L. G. D., Schurgers, L. J., Griffin, J. H., Koenen, R. R., & Hackeng, T. M. (2012). Incorporation of Disulfide Containing Protein Modules into Multivalent Antigenic Conjugates: Generation of Antibodies against the Thrombin-Sensitive Region of Murine Protein S. Journal of the American Chemical Society, 134(47), 19318-19321. https://doi.org/10.1021/ja306993t
    • Compeer, M. G., Suylen, D. P. L., Hackeng, T. M., & De Mey, J. G. R. (2012). Endothelin-1 and-2: Two amino acids matter. Life Sciences, 91(13-14), 607-612. https://doi.org/10.1016/j.lfs.2012.02.011
    • Peraramelli, S., Suylen, D. P. L., Rosing, J., & Hackeng, T. M. (2012). The Kunitz 1 and Kunitz 3 domains of tissue factor pathway inhibitor are required for efficient inhibition of factor Xa. Thrombosis and Haemostasis, 108(2), 266-276. https://doi.org/10.1160/TH11-12-0902
    • Compeer, M. G., Meens, M. J. P. M. T., Hackeng, T. M., Neugebauer, W. A., Hoeltke, C., & De Mey, J. G. R. (2012). Agonist-dependent modulation of arterial endothelinA receptor function. British Journal of Pharmacology, 166(6), 1833-1845. https://doi.org/10.1111/j.1476-5381.2012.01896.x
    • Chatrou, M. L. L., Winckers, K., Hackeng, T. M., Reutelingsperger, C. P. M., & Schurgers, L. J. (2012). Vascular calcification: The price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Reviews, 26(4), 155-166. https://doi.org/10.1016/j.blre.2012.03.002
    • Peraramelli, S., Rosing, J., & Hackeng, T. M. (2012). TFPI-dependent activities of Protein S. Thrombosis Research, 129, S23-S26. https://doi.org/10.1016/j.thromres.2012.02.024
    • Grommes, J., Alard, J-E., Drechsler, M., Wantha, S., Morgelin, M., Kuebler, W. M., Jacobs, M., von Hundelshausen, P., Markart, P., Wygrecka, M., Preissner, K. T., Hackeng, T. M., Koenen, R. R., Weber, C., & Soehnlein, O. (2012). Disruption of Platelet-derived Chemokine Heteromers Prevents Neutrophil Extravasation in Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine, 185(6), 628-636. https://doi.org/10.1164/rccm.201108-1533OC
    • Knottnerus, I. L. H., Winckers, K., ten Cate, H., Hackeng, T. M., Lodder, J., Rouhl, R. P. W., Staals, J., Govers-Riemslag, J. W. P., Bekers, O., & van Oostenbrugge, R. J. (2012). Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients. Neurology, 78(7), 493-498. https://doi.org/10.1212/WNL.0b013e318246d6b7
    • Van de Vijver, P., Scheer, L., van Beijnum, J., Griffioen, A., & Hackeng, T. M. (2012). Application of an omonasteine ligation strategy for the total chemical synthesis of the BRD7 bromodomain. Chemical Communications, 48(75), 9403-9405. https://doi.org/10.1039/c2cc34956f
  • 2011
    • Winckers, K., Siegerink, B., Duckers, C., Maurissen, L. F., Tans, G., Castoldi, E., Spronk, H. M. H., Ten Cate, H., Algra, A., Hackeng, T. M., & Rosendaal, F. R. (2011). Increased tissue factor pathway inhibitor activity is associated with myocardial infarction in young women: results from the RATIO study. Journal of Thrombosis and Haemostasis, 9(11), 2243-2250. https://doi.org/10.1111/j.1538-7836.2011.04497.x
    • Laeremans, H., Hackeng, T. M., van Zandvoort, M. A. M. J., Thijssen, V. L. J. L., Janssen, B. J. A., Ottenheijm, H. C. J., Smits, J. F. M., & Blankesteijn, W. M. (2011). Blocking of Frizzled Signaling With a Homologous Peptide Fragment of Wnt3a/Wnt5a Reduces Infarct Expansion and Prevents the Development of Heart Failure After Myocardial Infarction. Circulation, 124(15), 1626-U107. https://doi.org/10.1161/CIRCULATIONAHA.110.976969
    • Soehnlein, O., Wantha, S., Simsekyilmaz, S., Doering, Y., Megens, R. T. A., Mause, S. F., Drechsler, M., Smeets, R., Weinandy, S., Schreiber, F., Gries, T., Jockenhoevel, S., Moeller, M., Vijayan, S., van Zandvoort, M. A. M. J., Agerberth, B., Pham, C. C. T. N., Gallo, R. L., Hackeng, T. M., ... Weber, C. (2011). Neutrophil-Derived Cathelicidin Protects from Neointimal Hyperplasia. Science Translational Medicine, 3(103), 10. https://doi.org/10.1126/scitranslmed.3002531
    • Panizzi, P., Nahrendorf, M., Figueiredo, J-L., Panizzi, J., Marinelli, B., Iwamoto, Y., Keliher, E., Maddur, A. A., Waterman, P., Kroh, H. K., Leuschner, F., Aikawa, E., Swirski, F. K., Pittet, M. J., Hackeng, T. M., Fuentes-Prior, P., Schneewind, O., Bock, P. E., & Weissleder, R. (2011). In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation. Nature Medicine, 17(9), 1142-U153. https://doi.org/10.1038/nm.2423
    • Bastings, M. M. C., Helms, B. A., van Baal, I., Hackeng, T. M., Merkx, M. A. G., & Meijer, E. W. (2011). From Phage Display to Dendrimer Display: Insights into Multivalent Binding. Journal of the American Chemical Society, 133(17), 6636-6641. https://doi.org/10.1021/ja110700x
    • Sarabi, A., Kramp, B. K., Drechsler, M., Hackeng, T. M., Soehnlein, O., Weber, C., Koenen, R. R., & von Hundelshausen, P. (2011). CXCL4L1 inhibits angiogenesis and induces undirected endothelial cell migration without affecting endothelial cell proliferation and monocyte recruitment. Journal of Thrombosis and Haemostasis, 9(1), 209-219. https://doi.org/10.1111/j.1538-7836.2010.04119.x
    • Shoshan, M. S., Shalev, D. E., Adriaens, W., Merkx, M. A. G., Hackeng, T. M., & Tshuva, E. Y. (2011). NMR characterization of a Cu(I)-bound peptide model of copper metallochaperones: Insights on the role of methionine. Chemical Communications, 47(22), 6407-6409. https://doi.org/10.1039/c1cc11600b
  • 2010
    • Castoldi, E., Maurissen, L. F. A., Tormene, D., Spiezia, L., Gavasso, S., Radu, C. M., Hackeng, T. M., Rosing, J., & Simioni, P. (2010). Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency. Haematologica-the Hematology Journal, 95(9), 1563-1571. https://doi.org/10.3324/haematol.2010.021923
    • Borissoff, J. I., Heeneman, S., Kilinc, E., Kassak, P., Van Oerle, R., Winckers, K., Govers-Riemslag, J. W. P., Hamulyak, K., Hackeng, T. M., Daemen, M. J. A. P., Ten Cate, H., & Spronk, H. M. H. (2010). Early Atherosclerosis Exhibits an Enhanced Procoagulant State. Circulation, 122(8), 821-U145. https://doi.org/10.1161/CIRCULATIONAHA.109.907121
    • Thijssen, V. L., Barkan, B., Shoji, H., Aries, I. M., Mathieu, V., Deltour, L., Hackeng, T. M., Kiss, R., Kloog, Y., Poirier, F., & Griffioen, A. W. (2010). Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity. Cancer Research, 70(15), 6216-6224. https://doi.org/10.1158/0008-5472.CAN-09-4150
    • Oostendorp, M., Douma, K., Hackeng, T. M., Post, M. J., van Zandvoort, M. A. M. J., & Backes, W. H. (2010). Gadolinium-Labeled Quantum Dots for Molecular Magnetic Resonance Imaging: R-1 Versus R-2 Mapping. Magnetic Resonance in Medicine, 64(1), 291-298. https://doi.org/10.1002/mrm.22342
    • Meens, M. J. P. M. T., Compeer, M. G., Hackeng, T. M., van Zandvoort, M. A., Janssen, B. J. A., & De Mey, J. G. R. (2010). Stimuli of Sensory-Motor Nerves Terminate Arterial Contractile Effects of Endothelin-1 by CGRP and Dissociation of ET-1/ETA-Receptor Complexes. PLOS ONE, 5(6), 11. https://doi.org/10.1371/journal.pone.0010917
    • Maurissen, L. F. A., Castoldi, E., Simioni, P., Rosing, J., & Hackeng, T. M. (2010). Thrombin generation-based assays to measure the activity of the TFPI-protein S pathway in plasma from normal and protein S-deficient individuals. Journal of Thrombosis and Haemostasis, 8(4), 750-758. https://doi.org/10.1111/j.1538-7836.2010.03743.x
    • Oostendorp, M., Douma, K., Wagenaar, A., Slenter, J. M. G. M., Hackeng, T. M., van Zandvoort, M. A. M. J., Post, M. J., & Backes, W. H. (2010). Molecular Magnetic Resonance Imaging of Myocardial Angiogenesis After Acute Myocardial Infarction. Circulation, 121(6), 775-U85. https://doi.org/10.1161/CIRCULATIONAHA.109.889451
    • Castoldi, E., Simioni, P., Tormene, D., Rosing, J., & Hackeng, T. M. (2010). Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. Journal of Thrombosis and Haemostasis, 8(2), 294-300. https://doi.org/10.1111/j.1538-7836.2009.03712.x
    • Van de Vijver, P., Suylen, D. P., Dirksen, A., Dawson, P. E., & Hackeng, T. M. (2010). N-epsilon-(Thiaprolyl)-lysine as a Handle for Site-Specific Protein Conjugation. Biopolymers, 94(4), 465-474. https://doi.org/10.1002/bip.21485
    • Oostendorp, M., Douma, K., Hackeng, T. M., van Zandvoort, M. A. M. J., Post, M. J., & Backes, W. H. (2010). Pharmacokinetics of contrast agents targeted to the tumor vasculature in molecular magnetic resonance imaging. Contrast Media & Molecular Imaging, 5(1), 9-17. https://doi.org/10.1002/cmmi.361
  • 2009
  • 2008
    • Cranenburg, E. C., Vermeer, C., Koos, R., Boumans, M. L., Hackeng, T. M., Bouwman, F. G., Kwaijtaal, M., Brandenburg, V. M., Ketteler, M., & Schurgers, L. J. (2008). The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. Journal of Vascular Research, 45(5), 427-36. https://doi.org/10.1159/000124863