Publications

2024

CCL18 aggravates atherosclerosis by inducing CCR6-dependent T-cell influx and polarization
Anjana Singh, Adriaan O Kraaijeveld, Adelina Curaj, Kanin Wichapong, Linda Hammering, Saskia C.A. De Jager, Ilze Bot, Sergei P. Atamas, Theo Van Berkel, J. Wouter Jukema, Iain Comerford, Shaun Reuss McColl, Barend Mees, Gerry Nicolaes, Tilman Hackeng, Elisa Liehn, Frank Tacke and Erik A.L. Biessen, Frontiers in Immunology, section T Cell Biology, accepted for publication

M6229 protects against extracellular histone induced liver injury, kidney dysfunction and mortality in a rat model of acute hyperinflammation
Chris P. M. Reutelingsperger, Marion J. Gijbels, Henri M.H. Spronk, Rene Van Oerle, Roy Schrijver, Peter Ekhart, Sjef De Kimpe, Gerry A.F. Nicolaes, International Journal of Molecular Sciences, Biomolecules, special issue on “Heparin, Heparan Sulfate and Heparanase in Health and Disease”, accepted for publication

The IRAK-M death domain: A tale of 3 surfaces
Berke Gürkan, Hessel Poelman, Liza Perverzeva, Danielle Kruijswijk, Alex F. de Vos, Anouk Groenen, Edgar Elbert Nollet, Kanin Wichapong, Esther Lutgens, Tom Van Der Poll, Jiangfeng Du, Wiersinga W. Wiersinga, Gerry Nicolaes and Cornelis Van ‘T Veer, Front. Mol. Biosci.,  accepted for publication

2023

Elevated levels of citrullinated fibrinogen in patients with cancer
Tom Arfman, V. Zollet, N. van Es, F.T.M. Bosch, Gerry A.F. Nicolaes, Nicoletta Sorvillo, Jan Voorberg, European Journal of Haematology, accepted for publication

Design and characterization of novel activated protein C (APC) variants for the proteolysis of cytotoxic extracellular histone H3
Joram B. Huckriede, Daniëlle M.H. Beurskens, Karin C.C.A. Wildhagen, Chris P.M. Reutelingsperger, Kanin Wichapong, Gerry A.F. Nicolaes, Journal of Thrombosis and Haemostasis, accepted for publication.

Inhibition of neutral sphingomyelinase 2 by novel small molecule inhibitors results in decreased release of extracellular vesicles by vascular smooth muscle cells and attenuated calcification
Angelina Pavlic, Hessel Poelman, Grzegorz Wasilewski, Kanin Wichapong, Petra Lux, Cecile Maassen, Esther Lutgens, Leon J. Schurgers, Chris P. Reutelingsperger, and Gerry A.F. Nicolaes. IJMS: Early-Stage Drug Discovery: Advances and Challenges, Int J Mol Sci. 2023 Jan 19;24(3):2027. PMID: 36768348

Extracellular histone release by renal cells after warm and cold ischemic kidney injury: studies in an ex-vivo porcine kidney perfusion model
Tim C. van Smaalen, Danielle M.H. Beurskens, Jasper J.H.F.M. Kox, Rasheendra Polonia, Rein Vos, Hans Duimel, Willine J. van de Wetering, Carmen López-Iglesias, Chris P. Reutelingsperger, L.W. Ernest van Heurn, Carine J. Peutz-Kootstra, Gerry A.F. Nicolaes. PlosOne, PLoS One. 2023 Jan 20;18(1):e0279944. PMID: 36662718

2022

Multimodal Measurement of Glycocalyx Degradation during Coronary Artery Bypass Grafting
M.E. Bol, J.B. Huckriede, K.H.G. van de Pas, T. Delhaas, R. Lorusso, G.A.F. Nicolaes, J.E.M. Sels, M.C.G. van de Poll. Frontiers in Medicine, Nov 29;9:1045728., 2022. PMID: 36523784 

The role of extracellular histones in COVID-19
Femke de Vries, Joram Huckriede, Kanin Wichapong, Chris Reutelingsperger, Gerry A.F. Nicolaes. Journal of Internal Medicine, 2022 Nov 16. doi: 10.1111/joim.13585. PMID: 36382685

The influenza hemagglutinin stem antibody CR9114: evidence for a narrow evolutionary path towards universal protection
Jacopo Frallicciardi, Anna L. Beukenhorst, Clarissa M. Koch, Angela Phillips, Michael M.Desai, Kanin Wichapong, Gerry A.F. Nicolaes, Wouter Koudstaal, Galit Alter, Jaap Goudsmit. Frontiers in Virology, accepted for publication, 2022

Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification.
Pavlic A, Bahram Sangani N, Kerins J, Nicolaes G.A.F., Schurgers L, Reutelingsperger C. (2022) Int J Mol Sci. 2022 Aug 16;23(16):9178. PMID: 36012444

Impaired antibody response is associated with histone-release, organ dysfunction and mortality in critically ill Covid-19 patients
Rickard Lagedal, Oskar Eriksson, Anna Sörman, Joram B. Huckriede, Bjarne Kristensen, Stephanie Franzén, Anders Larsson, Anders Bergqvist, Kjell Alving, Anders Forslund, Barbro Persson, Kristina N. Ekdahl, Pablo Garcia de Frutos, Bo Nilsson, Gerry A. F. Nicolaes, Miklos Lipcsey, Michael Hultström, Robert Frithiof. (2022) Journal of Clinical Medicine,  Jun 14;11(12):3419. PMID: 35743491

Structure-Based Cyclic Glycoprotein Ibα-Derived Peptides Interfering with von Willebrand Factor-Binding, Affecting Platelet Aggregation under Shear.
Hrdinova J, Fernández DI, Ercig B, Tullemans BME, Suylen DPL, Agten SM, Jurk K, Hackeng TM, Vanhoorelbeke K, Voorberg J, Reutelingsperger CPM, Wichapong K, Heemskerk JWM, Gerry A.F.  Nicolaes. (2022) Int J Mol Sci. 2022 Feb 12;23(4):2046. PMID: 35216161

Structural anomalies in a published NMR-derived structure of IRAK-M.
Hessel Poelman, Hans Ippel, Berke Gürkan, Rolf Boelens, Gert Vriend, Cornelis van ‘t Veer, Esther Lutgens, Gerry A.F. Nicolaes  (2021) J Mol Graph Model. (2022) 2022 Mar;111:108061. doi: 10.1016/j.jmgm.2021.108061. PMID: 34837785

2021

Conformational plasticity of ADAMTS13 in hemostasis and autoimmunity
Bogac Ercig, Tom Arfman, Johana Hrdinova, Kanin Wichapong, Chris Reutelingsperger, Karen Vanhoorelbeke, Jan Voorberg, Gerry A.F. Nicolaes  (2021),  J Biol Chem. Aug 27;297(4):101132. doi: 10.1016/j.jbc.2021.101132. PMID: 34461090 

Design, synthesis, and biological evaluation of novel pyrrolidinone small-molecule Formyl Peptide Receptor 2 agonists
Monika Maciuszek, Almudena Ortega-Gomez, Sanne L. Maas, Jose Garrido-Mesa, Bartolo Ferraro, Mauro Perretti, Andy Merritt, Gerry A.F. Nicolaes, Oliver Soehnlein, Timothy M. Chapman (2021), Eur J Med Chem. Sep 2;226:113805. doi: 10.1016/j.ejmech.2021.113805. PMID: 34536667 

Histone H3 cleavage in severe COVID-19 ICU patients
Joram Huckriede, Femke de Vries, Michael Hulström, Kanin Wichapong, Chris Reutelingsperger, Miklos Lipcsey, Pablo Garcia de Frutos, Robert Frithiof, Gerry A.F. Nicolaes (2021), Front Cell Infect Microbiol. Sep 10;11:694186. doi: 10.3389/fcimb.2021.694186. PMID: 34568088

Evolution of NETosis markers and DAMPs have prognostic value in critically ill COVID-19 patients
Huckriede, J., Anderberg, S., Morales, A., de Vries, F., Hultström, M., Bergqvist, A., Ortiz, J.T., Sels, J-W., Wichapong, K., Lipcsey, M., van de Poll, M., Larsson, A., Luther, T., Reutelingsperger, C.P.M., Garcia de Frutos, P., Frithiof, R., Nicolaes, G.A.F., (2021) Sci Rep. 2021 Aug 3;11(1):15701. doi: 10.1038/s41598-021-95209-x. PMID: 34344929

Structure-function of anticoagulant TIX-5, the inhibitor of Factor Xa-mediated FV activation
Anja Maag, Priyanka Sharma, Tim J. Schuijt, Wil F. Kopatz, Daniëlle Kruijswijk, Arnoud Marquart, Tom van der Poll, Tilman M. Hackeng, Gerry A.F. Nicolaes, Joost C.M. Meijers, Mettine H.A. Bos, Cornelis van ’t Veer (2021) Journal of Thrombosis and Haemostasis, Jul;19(7):1697-1708. doi: 10.1111/jth.15329. Epub 2021 May 1. PMID: 33829620

PAD4 takes charge during neutrophil activation: impact of PAD4 mediated NET formation on immune-mediated disease
Xiaosong Liu, Tom Arfman, Kanin Wichapong, Chris P. M. Reutelingsperger, Jan Voorberg, Gerry A. F. Nicolaes (2021) Journal of Thrombosis and Haemostasis Jul;19(7):1607-1617. doi: 10.1111/jth.15313. Epub 2021 May 12. PMID: 33773016

The vitamin K-dependent protein GAS6 is increased in COVID-19 and predicts patient outcome
Albert Morales, Silvia Rojo, Helena Cristóbal, Aida Fiz-López, Elisa Arribas, Paloma de la Cal; Gerry A.F. Nicolaes, José T. Ortiz, David Bernardo, Pablo García de Frutos (2021) Biomedicines,9(4):335. doi 10.3390/biomedicines9040335. PMID: 33810394 

N-glycan mediated shielding of ADAMTS13 prevents binding of pathogenic autoantibodies in immune-mediated TTP
Bogac Ercig, Nuno Alexandre Gomes Graca, Kadri Kangro, Tom Arfman, Kanin Wichapong, Johana Hrdinova, Paul Kaijen, Floris van Alphen, Maartje van den Biggelaar, Karen Vanhoorelbeke, Agnès Veyradier, Paul Coppo, Chris Reutelingsperger, Gerry A F Nicolaes, Andres Männik, Jan Voorberg (2021) Blood, Feb 5;blood.2020007972.doi: 10.1182/blood.2020007972. PMID: 33544829

Autocitrullination of PAD4 does not alter its enzymatic activity: in vitro and in silico studies
Xiaosong Liu, Kanin Wichapong, Bas Lamers, Chris. P.M. Reutelingsperger, Gerry A. F. Nicolaes (2021) International Journal of Biochemistry and Cell Biology, 2021 Jan 30:105938. doi: 10.1016/j.biocel.2021.105938. PMID: 33529715

Structure-Based Peptide Design Targeting Intrinsically Disordered Proteins: Novel Histone H4 and H2A Peptidic Inhibitors
Kanin Wichapong, Carlos Silvestre-Roig, Quinte Braster, Ariane Schumski, Oliver Soehnlein, Gerry A. F. Nicolaes (2021) Comput Struct Biotechnol J., Jan 21;19:934-948. doi: 10.1016/j.csbj.2021.01.026. PMID: 33598107

2020

Endotoxinemia accelerates atherosclerosis via electrostatic charge-mediated monocyte adhesion
Ariane Schumski,  Almudena Ortega-Gómez, Kanin Wichapong, Carla Winter, Patricia Lemnitzer, Joana R. Viola, Mayra Pinilla, Eduardo Folco, Victor Solis-Mezarino, Moritz Völker-Albert, Sanne L. Maas, Chang Pan, Laura Perez Olivares, Janine Winter, Tilman Hackeng, Mikael Karlsson, Tanja Zeller, Axel Imhof, Rebecca M Baron, Gerry Nicolaes, Peter Libby, Lars Maegdefessel, Frits Kamp, Martin Benoit, Yvonne Döring, Oliver Soehnlein. (2020) Circulation, Jan 19;143(3):254-266. doi: 10.1161. PMID: 33167684

Role of Vitamin K Factors and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis
Tutusaus, A., Marí, M., Ortiz-Pérez, J.T., Nicolaes, G.A.F., Morales, A., García de Frutos, P. (2020) Cells, Sep 28;9(10):2186. doi: 10.3390/cells9102186. PMID: 32998369

Neutrophils and Contact Activation of Coagulation as Potential Drivers of Covid-19
Busch, M., Timmermans, S., Nagy, M., Visser, M., Huckriede, J., Aendekerk, J., de Vries, F., Potjewijd, J., Jallah, B., Ysermans, R., Oude Lashof, A., Breedveld, P., van de Poll, M., van der Horst, I., van Bussel, B., Theunisssen, R., Spronk, H., Damoiseaux, J., Ten Cate, H., Nicolaes, G.A.F., Reutelingsperger, C.P.M. and Pieter van Paassen, (2020) Circulation, Nov 3;142(18):1787-1790. PMID: 32946302

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort; MaastrICCht
Tas, J., van Gassel, R.J.J., Heines, S.J.H., Mulder, M.M.G., Heijnen, N.F.L., Acampo-de Jong, M.J., Bels,   J.L.M., Bennis, F.C., Koelmann, M., Groven, R.V.M., Donkers, M.A., van Rosmalen, F., Hermans, B.J.M., Meex, S.J.R., Mingels, A.M.A., Bekers, O., Savelkoul, P.H.M., Oude Lashof, A.M.L, Wildberger, J.E., Tijssen, F.H., Buhre, W.F.F.A., Sels, J.E.M., Ghossein-Doha, C., Driessen, R.G.H., Kubben, P.L., Janssen, M.L.F., Nicolaes, G.A.F., Strauch,  U., Geyik, Z., Delnoy, T.S.R., Walraven, K.H.M., Stehouwer, C.D.A., Verbunt, J.A.M.C.F., van Mook, W.N.K.A, van Santen, S., Schnabel, R.M., Aries, M.J.H., van de Poll, M.C.G. Bergmans, , D.C.J.J, van der Horst, I.C.C., van Kuijk, S.M.J., van Bussel, B.C.T.  (2020) British Medical Journal Open, 2020 Sep 29;10(9):e040175. doi: 10.1136/bmjopen-2020-040175. PMID: 32994259

The anticoagulant and nonanticoagulant properties of heparin
Beurskens, D.M.H., Huckriede, J.P., Schrijver, R., Hemker, H.C., Reutelingsperger, C.P.M., Nicolaes, G.A.F (2020) Thrombosis and Haemostasis, Oct;120(10):1371-1383. doi: 10.1055/s-0040-1715460. PMID: 32820487

Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis
Beurskens, D.M.H., Bol, M.E., Delhaas, T., van de Poll, M.C.G., Reutelingsperger, C.P.M., Nicolaes, G.A.F., Sels, J.W.E.M. (2020) Anaesth Intensive Care. 2020 May;48(3):221-228. PMID: 32486831

2019

Modifying ADAMTS13 to modulate binding of pathogenic autoantibodies of patients with acquired thrombotic thrombocytopenic purpura
Graca, N.A.G., Ercig, B., Velasquez Pereira, L.C., Kangro, K., Kaijen, P., Nicolaes, G.A.F., Veyradier, A., Coppo, P., Vanhoorelbeke, K., Männik, A., Voorberg, J. (2019) Haematologica,
2019 Nov 21. pii: haematol.2019.226068. doi: 10.3324/haematol.2019.226068. PMID:31753929

Variability of microcirculatory measurements in critically ill patients
M.E. Bol, D.M.H. Beurskens, T.S.R. Delnoij, P.M.H.J. Roekaerts, C.P.M. Reutelingsperger, T. Delhaas, M.C.G. van de Poll, J.W.E.M. Sels, G.A.F. Nicolaes (2019) Shock,
Shock, Nov 15. Doi: 10.1097/SHK.0000000000001470. PMID:31743299

A Synthetic Triple Helical Collagen Peptide as a New Agonist for Flow Cytometric Measurement of GPVI Specific Platelet Activation
Sang, Y., Huskens, D., Wichapong, K., de Laat, B., Nicolaes, G.A.F., Roest, M. (2019) Thrombosis and Haemostasis, Oct 21. doi: 10.1055/s-0039-1697660. 
PMID: 31634956

Protection against neutrophil extracellular trap (NET) toxicity by antioxidant monoHER
Astuti, P., Beurskens, D.M.A., Vajen, T., Nicolaes, G.A.F., Zhang, M., Haenen, G.R.M.M. (2019) Makara J Health Res.;23(2):108–15

Acetaminophen-overdose as a potential risk factor for Parkinson’s disease
Bohler, S., Liu, X., Krauskopf, J., Caiment, F., Briedé, J., Aubrecht, J., Nicolaes, G., Kleinjans, J. (2019) Clinical and Translational Science, Jul 15. doi: 10.1111/cts.12663.PMID:31305025

Rational Modulator Design by Exploitation of Protein-Protein Complex Structures
Wichapong, K., Poelman, H., Ercig, B., Hrdinova, J., Liu, X., Lutgens, E. and Nicolaes, G.A.F. (2019) Future Medicinal Chemistry, May;11(9):1015-1033. doi: 10.4155/fmc-2018-0433.PMID:31141413

Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Carlos Silvestre-Roig, Quinte Braster, Kanin Wichapong,….., Gerry A.F. Nicolaes, Gerard C. L. Wong, Oliver Soehnlein (2019) Nature, May;569(7755):236-240. doi: 10.1038/s41586-019-1167-6.PMID:31043745

Deficiency of the T cell regulator CBL-B aggravates atherosclerosis by inducing CD8+ T cell-mediated macrophage death
Seijkens, T.T.P., Poels, K., Meiler, S., van Tiel, C.M., Kusters, P.J.H., Reiche, M., Atzler, D., Winkels, H.,  Tjwa, M., Poelman, H., Slütter, B., Kuiper, J., Gijbels, M., Kuivenhoven, J.A., Matic, L.P., Paulsson-Berne, G., Hedin, U., Hansson, G.K., Nicolaes, G.A.F., Daemen, M.J.A.P., Weber, C., Gerdes, N., de Winther, M., and Esther Lutgens (2019) Eur Heart J, Jan 21;40(4):372-382.PMID:30452556

2018

Inhibiting  inflammation  with  myeloid  cell-specific  nanobiologics  promotes  organ transplant  acceptance
Braza, M.S.,  van  Leent, M.M.T., Lameijer, M., Sanchez- Gaytan, B.L.,  Arts, R.J.W., Pérez-Medina, C., Conde, P., Garcia, M.R., Gonzalez-Perez, M., Brahmachary, M., Fay, F., Kluza, E., Kossatz, S., Dress, R.J.,  Salem, F., Rialdi, A., Reiner, T., Boros, P., Strijkers, G.J., Calcagno, C.C., Ginhoux, F., Marazzi, I., Lutgens, E., Nicolaes, G.A.F., Weber, C., Swirski, F.K., Nahrendorf, M., Fisher, E.A., Duivenvoorden, R., Fayad, Z.A., Netea, M.G., Mulder, W.J.M., Ochando, J (2018) Immunity, 2018 Nov 20;49(5):819-828.e6.PMID:30413362

Child-onset thrombotic thrombocytopenic purpura caused by p.R498C and p.G259PfsX133 mutations
Schelpe A., Orlando C., Ercig B., Geeroms C., Pareyn I., Vandeputte N., Velásquez P., Leydi C.,  Roose E., Fostier K., Nicolaes G., Deckmyn H., De Meyer S., Vanhoorelbeke K., Jochmans K. (2018) European Journal of Haematology, May 15. doi: 10.1111/ejh.13094. PMID:29763513

Chrono-pharmacological targeting of the CCL2-CCR2 axis ameliorates atherosclerosis
Winter, C., Silvestre-Roig, C., Ortega-Gomez, A., Lemnitzer, P., Poelmann, H., Schumski,A., Winter, J., Drechsler, M., de Jong, R., Immler, R., Sperandio, M., Hristov, M., Zeller, T., Nicolaes, G.A.F., Weber, C., Viola, J.R., Hidalgo, A., Scheiermann, C., Soehnlein, O. (2018) Cell Metabolism, Jul 3;28(1):175-182.e5. doi: 10.1016/j.cmet.2018.05.002. PMID:29861387

TRAF-STOPping atherosclerosis: targeting of CD40-induced TRAF6 signaling in macrophages reduces (established) atherosclerosis
Seijkens, T.T.P., van Tiel, C.M., Kusters, P.J.H., Pascal, J.H., Atzler, D., Soehnlein, O., Zarzycka, B., Aarts, S.A.B.M., Lameijer, M., M.A., Gijbels, M.J., Beckers, L., den Toom, M., Slütter, B., Kuiper, J., Duchene, J., Aslani, M., Megens, R., van ‘t Veer, C., Kooij, G., Schrijver, R., Hoekseman, M., Boon, L., Fay, F., Tang, J., Baxter, S., Jongejan, A., Moerland, P.D., Vriend, G., Bleijlevens, B., Fisher, E.A., Duivenvoorden, R., Gerdes, N., de Winther, M.P.J., Nicolaes, G.A.F., Mulder, W.J.M., Weber, C., Lutgens, E.
(2018) The Journal of the American College of Cardiology, 71(5) 527-42. PMID:29406859

Insights into 3D-structure of ADAMTS13: a stepping stone towards novel therapeutic treatment of TTP
Ercig, B, Wichapong, K, Reutelingsperger, CPM, Vanhoorelbeke, K, Voorberg, J, Nicolaes, GAF
(2017) Journal of Thrombosis and Haemostasis, Jan;118(1):28-41.
PMID:29304523

2017

Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002 reduces neuroinflammation.
Aarts SABM, Seijkens TTP, Kusters PJH, van der Pol SMA, Zarzycka B, Heijnen PDAM, Beckers L, den Toom M, Gijbels MJJ, Boon L, Weber C, de Vries HE, Nicolaes GAF, Dijkstra CD, Kooij G, Lutgens E.
(2017) J Neuroinflammation. 2017 May 12;14(1):105.
PMID:28494768

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.
von Hundelshausen P, Agten SM, Eckardt V, Blanchet X, Schmitt MM, Ippel H, Neideck C, Bidzhekov K, Leberzammer J, Wichapong K, Faussner A, Drechsler M, Grommes J, van Geffen JP, Li H, Ortega-Gomez A, Megens RT, Naumann R, Dijkgraaf I, Nicolaes GAF, Döring Y, Soehnlein O, Lutgens E, Heemskerk JW, Koenen RR, Mayo KH, Hackeng TM, Weber C.
(2017) Sci Transl Med. 2017 Apr 5;9(384).
PMID:28381538

Presence of Cytotoxic Extracellular Histones in Machine Perfusate of Donation After Circulatory Death Kidneys.
van Smaalen, T.C., Beurskens, D., Hoogland, E.R.P., Winkens, B.,  Christiaans, M.H.L, Reutelingsperger, C.P., van Heurn, L.W.E., and G.A.F. Nicolaes
(2017) Transplantation, Apr;101(4):e93-e101.
PMID:27906828

2016

Structure-based design of peptidic inhibitors of the interaction between CCL5 and HNP1.
Wichapong, K., Alard, J., Ortega-Gomez, A., Weber, C., Hackeng, T.M., Soehnlein, O. and G.A.F. Nicolaes.
(2016) J Med Chem, May 12;59(9):4289-301.PMID:26871718

Pharmacological targeting of AMP-activated protein kinase and opportunities for computer-aided drug design.
Miglianico, M., Nicolaes, G.A.F., Neumann, D.
(2016) J Med Chem, 2016 Apr 14;59(7):2879-93. PMID:26510622

Stabilisation of protein-protein interaction complexes through small molecules.
Zarzycka, B., Kuenemann, M.A., Miteva, M., Nicolaes, G.A.F., Vriend, G., Sperandio, O.
(2016) Jan;21(1):48-57. Drug Disc Today. PMID:26434617

iPPI-DB: an online database of modulators of protein-protein interactions.
Labbé, C.M., Kuenemann, M.A., Zarzycka, B., Vriend, G., Nicolaes, G.A.F., Lagorce, D., Miteva, M.A., Villoutreix, B.O., Sperandio, O.
(2016) Nucleic Acids Res.; Jan 4;44(D1):D542-7. PMID:26432833

2015

Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5.
Alard, J.-E., Ortega-Gomez, A., Wichapong, K., Bongiovanni, D., Horckmans, M., Megens, R.T.A., Leoni, G., Ferraro, B., Rossaint, J., Paulin, N., Ng, J., Ippel, H., Suylen, D., Hinkel, R., Blanchet, X., Gaillard, F., D’Amico. M., von Hundelshausen, P., Zarbock, A., Scheiermann, C., Hackeng, T.M., Steffens, S., Kupatt, C., Weber, C., Nicolaes, G.A.F., and O. Soehnlein
(2015) Sience Transl Med.; 7(317):317ra196. PMID:26659570

Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients.
Wildhagen, K.C.A.A., Wiewel, M.A., Schultz, M.J., Horn, J., Schrijver, R., Reutelingsperger, C.P.M., van der Poll, T., Nicolaes, G.A.F.
(2015) Thromb. Res.; 136(3):542-7. PMID:26232351

Identification of small molecule inhibitors against SecA by structure-based virtual ligand screening.
De Waelheyns, E., Segers, K., Sardis, M., Anné, J., Nicolaes, G.A.F. and Economou, A.
(2015), Journal of Antibiotics Nov;68(11):666-73. PMID:25990955

Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis.
Zarzycka, B., Nicolaes, G.A.F., Lutgens, E.
(2015) Expert Review of Clinical Pharmacology, 8(3):297-313. PMID:25843158

Two Novel Mutations in the SLC25A4 Gene in a Patient with Mitochondrial Myopathy.
Körver-Keularts IM, de Visser M, Bakker HD, Wanders RJ, Vansenne F, Scholte HR, Dorland L, Nicolaes GAF, Spaapen LM, Smeets HJ, Hendrickx AT, van den Bosch BJ.
(2015) JIMD Rep. 22; 39-45. PMID:25732997

Discovery of small molecule CD40-TRAF6 inhibitors.
Zarzycka, B., Seijkens, T., Nabuurs, S.B., Ritschel, T., Grommes, J., Soehnlein, O., Schrijver, R., van Tiel, C.M., Hackeng, T.M., Weber, C., Giehler, F., Kieser, A., Lutgens, E., Vriend, G. and Nicolaes, G.A.F.
(2015), Journal of Chemical Information and Modeling, Feb 23;55(2):294-307. PMID:25622654

Molecular simulation studies of human coagulation factor VIII C domain-mediated membrane binding.
Du, J., Wichapong, K., Hackeng, T. and Nicolaes, G.A.F.
(2015) Thrombosis and Haemostasis, Jan 27;113(2):373-84. PMID:25354705

2014

The Structure Function of the Death Domain of human IRAK-M.
Du, J., Nicolaes, G.A.F., Kruijswijk, D., Versloot, M., van der Poll, T. and van ’t Veer, C.
(2014), Cell Communication and Signaling.
Dec 7;12(1):77. PMID:25481771

Blocking CD40-Traf6 interactions by small molecule inhibitor 6860766 ameliorates the complications of diet induced obesity in mice.
Van den Berg, S., Seijkens, T., Kusters, P., Zarzycka, B., Beckers, L., den Toom, M., Gijbels, M., Chatzigeorgiou, A., Weber, C., de Winther, M., Chavakis, T., Nicolaes, G.A.F. and Lutgens, E.
(2014), Int J Obes (Lond). 39(5):782-90. PMID:25394307

Understanding the functional difference between growth arrest-specific protein 6 (GAS6) and protein S (PROS1): an evolutionary approach.
Studer, R.A., Opperdoes, F.R., Nicolaes, G.A.F., Mulder, A.B. and Mulder, R.
(2014) Open Biol. Oct;4(10). pii: 140121. doi: 10.1098/rsob.140121. PMID:25339693

Factor Va alternative conformation reconstruction using Atomic Force Microscopy.
Chaves, R.C., Dahmane, S., Odorico, M., Nicolaes, G.A.F., and J.-L. Pellequer
(2014) Thromb Haemost. 2014 Sep 4;112(6). PMID:25185589

Effects of exogenous recombinant APC in mouse models of ischemia reperfusion injury and of atherosclerosis.
Wildhagen, K.C.A.A., Schrijver, R., Beckers, L., ten Cate, H., Reutelingsperger, C.P., Lutgens, E., Nicolaes, G.A.F.
(2014) PLOS ONE, Jul 17;9(7):e101446. PMID:25032959

Identification of novel small molecule inhibitors of activated protein C.
Sperandio, O.,Wildhagen, K.C.A.A., Schrijver, R., Wielders, S., Villoutreix, B.O., Nicolaes, G.A.F.
(2014) Thromb. Res.; 133(6):1105-14. PMID:24513148

Blocking CD40‐TRAF6 signaling is a novel therapeutic target in obesity‐associated insulin resistance.
Chatzigeorgiou, 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., Klotzsche-von Ameln, A., Gijbels, M., Noelle, R., Boon, L., Hackeng, T.M., Schulte, K., Xu, A., Vriend, G., Nabuurs, S., Chung, K., Willems van Dijk, K., Rensen, P.C.N., Gerdes, N., Winther, M., Block, N.L., Schally, A.V., Weber, C., Bornstein, S.R., Nicolaes, G.A.F., Chavakis, T., Lutgens, E. shared last authors
(2014) Proc. Natl. Acad. Sci., U S A. 2014 Feb 18;111(7):2686-91. PMID:24492375

Non-anticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis.
Wildhagen, K.C.A.A., García de Frutos, P., Reutelingsperger, C.P., Schrijver, R., Aresté, C., Ortega-Gómez, A., Deckers, N.M., Hemker, H.C., Soehnlein, O., Nicolaes, G.A.F.
(2014) Blood 13;123(7):1098-101. PMID:24264231

Rational design of small molecules targeting the C2 domain of coagulation factor VIII.
Nicolaes, G.A.F., Kulharia, M., Voorberg, J., Kaijen, P.H., Wroblewska, A., Wielders, S., Schrijver, R., Sperandio, O., Villoutreix, B.O.
(2014) Blood; 123(1):113-20. PMID:24227818

Optimization of compound ranking for structure-based virtual ligand screening using an established FRED-Surflex consensus approach.
Du, J., Bleylevens, I.W.M., Bitorina, A.V., Wichapong, K., Nicolaes, G.A.F.
(2014) Chemical Biology and Drug Design; 83(1):37-51. PMID:23941463

2013

Factor Xa-induced activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein.
Schuijt, T.J., Bakhtiari, K., Daffre, S., DePonte, K., Wielders, S.J.H., Marquart, J.A., Hovius, J.W., van der Poll, T., Fikrig, E., Bunce, M.W., Camire, R.M., Nicolaes, G.A.F., Meijers, J.C.M. and van ’t Veer, C.
(2013) Circulation;128(3):254-66. PMID:23817575

Two novel mutations in the prothrombin gene identified in a patient with compound heterozygous type 1/2 prothrombin deficiency.
Kuijper P.H., Schellings M.W., van de Kerkhof D., Nicolaes G.A.F., Reitsma P., Halbertsma F., Dors N.
(2013) Haemophilia, May28. PMID:23711336

2012

Comparative Analysis of Pharmacophore Screening Tools.
Sanders MP, Barbosa AJ, Zarzycka B, Nicolaes GA, Klomp JP, de Vlieg J, Del Rio A.
(2012) J Chem Inf Model. 52(6): 1607-20 PMID: 22646988

Goodpasture Antigen-binding Protein/ceramide Transporter Binds to Human Serum Amyloid P-component and is presentin Brain Amyloid Plaques.
Mencarelli C, Bode GH, Losen M, Kulharia M, Molenaar PC, Veerhuis R, Steinbusch HW, De Baets MH, Nicolaes GAF, Martinez-Martinez P.
(2012) J Biol Chem 287(18): 14897-911 PMID: 22396542    

De structuur-functie relatie van geactiveerd protein C: wat mutaties ons kunnen leren.
Wildhagen, K.C.A.A., Lutgens, E.,  Loubele S.T.B.G., ten Cate, H.,Nicolaes, G.A.F.
(2012) Tromnibus, 40;2:29-32 (in Dutch)   

2011

APC Resistance. Gerry A.F. Nicolaes (2011). in: Thrombophilia, Andrea Luigi Tranquilli (Ed.), ISBN: 978-953-307-872-4, InTech
http://www.intechopen.com/articles/show/title/apc-resistance

The structure-function relationship of activated protein C: lessons from natural and engineered mutations.
Wildhagen K.C.A.A., Lutgens E., Loubele S.T.G.B, ten Cate H and Nicolaes G.A.F.
(2011) Thromb. Haemostas, Nov 10;106(6) PMID: 22072231

Engineered annexin A5 variants with impaired cell entry for molecular imaging of apoptosis using pretargeting strategies.
Ungethum L., Kenis H., Nicolaes G.A.F., Autin L., Stoilova-McPhie S., Reutelingsperger C.P.
(2011) J Biol Chem. 286(3):1903-1910 PMID: 21078669

Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.
Gerards M., van den Bosch B.J., Danhauser K., Serre V., van Weeghel M., Wanders R.J., Nicolaes G.A.F., Sluiter W., Schoonderwoerd K., Scholte H.R., Prokisch H., Rötig A., de Coo I.F., Smeets H.J.
(2011) Brain. 134(1): 210-219 PMID: 20929961

2010

Trp2313-His2315 of the FVIII C2 domain are involved in membrane binding: Structural analysis of a complex between the C2 domain and an inhibitor of membrane binding.
Liu, Z., Lin, L., Yuan, C., Nicolaes, G.A.F., Chen, L., Meehan, E.J., Furie, B., Furie, B., Huang, M.
(2010) J. Biol. Chem.285(12):8824-9 PMID: 20089867

Inhibition of thrombin formation by active site Ser360 to Ala-substituted activated protein C.
Nicolaes, G.A.F., Bock, P.E., Segers, K., Wildhagen, K.C.A.A., Dahlback, B., Rosing, J.
(2010) J. Biol. Chem. May 18. 48. PMID: 20484050

The D2194G mutation is responsible for increased levels of FV1 in carriers of the factor V R2 haplotype.
Yamazaki, T. Okada, H., Balling, K.W., Dahlbäck, B., Nicolaes, G.A.F.
(2010) Thromb. Haemostas. Oct;104(4):860-1

2009

FVIII-eGFP fusion proteins with preserved functional activity for the analysis of the early secretory pathway of FVIII.
Heinz, S., Schüttrumpf, J., Simpson, J.C., Pepperkok, R., Nicolaes, G.A.F., Seifried, E.,  Tonn, T.
(2009) Thrombosis and Haemostasis, Thromb Haemost. (2009);102(5):925-35 PMID: 19888531

Factor IX Mutants with Enhanced Catalytic Activity.
Hartmann, R.,  Dockal, M., Kammlander, W., Fiedler, C., Panholzer, E., Nicolaes, G.A.F., Rosing, J. and Scheiflinger, F.
(2009) Journal of Thromb. Haemost., 7(10):1656-62 PMID: 19656280

2008

Multimerin 1 inhibits thrombin generation and binds factor V and Va with high affinity.
Jeimy, S.B., Fuller, N., Quin-Allen, M.A., Tasneem, S. Segers, K., Stafford, A.R., Weitz, J.I., Camire, R.M., Nicolaes, G.A.F., Kane, W.H., Hayward, C.P.M.
(2008) J Biol Chem, Thromb Haemost., 100(6):1058-67.PMID: 19132231

Screening Outside the Catalytic Site: Inhibition of Macromolecular Inter-actions Through Structure-Based Virtual Ligand Screening Experiments.
Sperandio O, Miteva MA, Segers K, Nicolaes GA, Villoutreix BO.
(2008) Open Biochem J. 2008;2:29-37. PMID: 18949072

Identification of surface epitopes of human coagulation factor Va which are important for interaction with activated protein C and heparin.
Segers, K., Dahlbäck, B., Rosing, J., Nicolaes, G.A.F.
(2008) J Biol Chem, 283(33):22573-81 PMID: 18519572

Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation.
Maurissen, L.F.A., Thomassen, M.C.L.G.D., Nicolaes, G.A.F., Dahlbäck, B., Tans, G., Rosing, J. and  Hackeng, T.M.
(2008) Blood 111(6):3034-41. PMID: 18160668

PROS1 Analysis in 87 Pedigrees with Hereditary Protein S Deficiency Demonstrates Striking Genotype-Phenotype Associations.
ten Kate, M., Platteel, M., Mulder, R., Terpstra, P. Nicolaes, G.A.F., Reitsma, P., van der Steege, G., van der Meer, J.
(2008) Human Mutation, 29(7), 939-47. PMID: 18435454

Defining the structure of membrane-bound human blood coagulation Factor Va.
Stoilova-McPhie, S., Awosile. F., Parmenter, C.D.J., Segers, K., Villoutreix, B.O., Nicolaes, G.A.F.
(2008) J Thromb Haemost. 6: 76-82. PMID: 17949476

2007

The role of thrombin exosites I and II in the activation of human coagulation factor V.
Segers, K., Dahlbäck, B., Bock, P.E., Tans, G.,Rosing, J., Nicolaes, G.A.F.
(2007) J Biol Chem.  282(47):33915-33924. PMID: 17878169

Coagulation factor V and thrombophilia: background and mechanisms.
Segers, K., Dahlbäck, B., Nicolaes, G.A.F.
(2007) Thrombosis and Haemostasis, 98(3): 530-542. PMID: 17849041

Design of protein-membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V.
Segers, K., Sperandio, O., Sack, M., Fischer, R., Miteva, M., Rosing, J., Nicolaes, G.A.F., Villoutreix, B.O.
(2007) Proc. Natl. Acad. Sci. 104 (31):12697-702. PMID: 17646652

Expression of allosteric linkage between the sodium ion binding site and exosite I of thrombin during prothrombin activation.
Kroh, H.K., Tans, G., Nicolaes, G.A.F., Rosing, J., Bock, P.E.
(2007) JBC, J Biol Chem. 282(22):16095-104. PMID: 17430903

2006

Biochemical, molecular characterization and glyco-proteomic analyses of alpha1-proteinase inhibitor products used for replacement therapy.
Kolarich, D., Turecek, P.L., Weber, A., Mitterer, A., Graninger, M., Matthiessen, P., Nicolaes, G.A.F., Altmann, F., Schwarz, H.P.
(2006) Transfusion 46(11):1959-77.  PMID: 17076852

A structural model of the SHBG domain of human variant protein S Heerlen.
Nicolaes, G.A.F., Hackeng, T.M., Segers, K., Rosing, J.
(2006) Thromb Haemost. 96(4):538-40. PMID: 17003935

Structural Models of the Snake Venom Factor V activators from Daboia russelli and Daboia lebetina.
Segers, K., Rosing, J., Nicolaes, G.A.F.
(2006). Proteins 64(4):968-84. PMID: 16807918

Activation of Factor V by Venom Proteases.
Nicolaes,G.A.F., Rosing, J.
(2006) Toxin Reviews 25(3):217-234. DOI: 10.1080/15569540600567289

2004

Identification of the MMRN1 binding region within the C2 domain of human factor V.
Jeimy, S.B., Woram, R.A., Fuller, N., Quinn-Allen, M.A., Nicolaes, G.A.F., Dahlbäck, B., Kane, W.H., Hayward, C.P.
(2004) J Biol Chem., 279(49):51466-71. PMID: 15452129

Altered inactivation pathway of factor Va by activated protein C in the presence of heparin.
Nicolaes G.A.F., Sörensen, K.W., Friedrich, U., Tans, G., Rosing, J.,  Autin L. , Dahlbäck B., Villoutreix B.O.
(2004) Eur J Biochem., 271(13):2724-36. PMID: 15206937

Impaired APC-cofactor activity of factor V is a major component of the APC resistance associated with the FV Leiden (R506Q) and R2 (H1299R) mutations.
Castoldi, E., Brugge, J.M., Nicolaes, G.A.F., Tans, G., Rosing, J.
(2004) Blood, 103(11):4173-9. PMID: 14976057

Functional Properties of Recombinant Factor V mutated in a Potential Calcium-Binding Site.
Sörensen, K.W., Nicolaes, G.A.F., Villoutreix, B.O., Yamazaki, T., Tans, G., Rosing, J., Dahlbäck, B.
(2004) Biochemistry, 43(19):5803-10. PMID: 15134454

Welke factor laat ons bloed stollen?
Nicolaes, G.A.F.
(2004) Chemisch2Magazine, 100(2): 18-19 (in Dutch)

Theoretical and experimental study of the Asp2194Gly mutation in the C2 domain of coagulation factor V.
Miteva, M.A., Brugge, J.M., Rosing, J., Nicolaes, G.A.F., Villoutreix, B.O.
(2004) Biophys. J., 86(1): 488-98. PMID: 14695293

2003

Congenital and Acquired Activated Protein C Resistance.
Nicolaes, G.A.F., Dahlbäck, B.
(2003). Seminars in Vascular Medicine, 3, 33-46. PMID: 15199491

Activated protein C resistance (FVLeiden) and thrombosis: factor V mutations causing hypercoagulable states.
Nicolaes, G.A.F., Dahlbäck, B.
(2003) Hematology and Oncology Clinics of North America, 17, 1-25. PMID: 12627662

2002

Structure-function studies of blood coagulation proteins using recombinant human factor V molecules.
Nicolaes, G.A.F., Tans, G., Rosing, J. Progress Report CARIM, University Maastricht (2002) 50-54.

Molecular basis of quantitative factor V deficiency associated with factor V R2 haplotype.
Yamazaki, T., Nicolaes, G.A.F., Winther Sørensen, K., Dahlbäck, B.
(2002) Blood, 100, 2515-2521. PMID: 12239164

Reduced factor V concentration and altered factor V1/factor V2 ratio do not fully explain R2-associated APC-resistance.
Govers-Riemslag, J., Castoldi, E., Nicolaes, G.A.F., Tans, G., Rosing, J.
(2002) Thrombosis and Haemostasis, 88, 444-449. PMID: 12353074

Factor V and Thrombotic disease: description of a Janus-faced protein.
Nicolaes, G.A.F., Dahlbäck, B.
(2002) Arteriosclerosis, Thrombosis, and Vascular Biology, 22(4), 530-538. PMID: 11950687

2001

Factor V.
Nicolaes G.A.F., Dahlbäck B.
(2001) Encyclopedia of Molecular Medicine, T.E. Creighton, ed., John Wiley and Sons, Inc., New York, 1231-1234.  ISBN 10: 0471374946

Introduction to structural bioinformatics; applications to blood coagulation factor V and factor VIII.
Bruno O. Villoutreix, Gerry A. F. Nicolaes, Martine Aiach
(2001) Hématologie, 7(4), 287-296. (in French) link

Secondary substrate-binding exosite in the serine protease domain of activated protein C important for cleavage at Arg-506 but not at Arg-306 in factor Va.
Friedrich U., Nicolaes G.A.F., Villoutreix B.O., Dahlbäck B.
(2001) Journal of Biological Chemistry, 276(25), 23105-23108. PMID: 11309403

2000

The second Laminin G-type domain of protein S is indispensable for full cofactor activity in activated protein C-catalyzed inactivation of factor Va and factor VIIIa.
Evenäs, P., Garcia de Frutos, P., Nicolaes, G.A.F., Dahlbäck, B.
(2000) Thrombosis and Haemostasis, 84(2),271-277. PMID: 10959700

Mutations in a potential phospholipid binding loop in the C2 domain of factor V affecting the assembly of the prothrombinase complex.
Nicolaes, G.A.F., Villoutreix, B.O., Dahlbäck, B.
(2000) Blood Coagulation & Fibrinolysis, 11, 89-100. PMID: 10691103

1999

Acquired APC resistance and oral contraceptives: A randomised cross-over study of two low dose oral contraceptives.
Rosing, J., Middeldorp, S., Curvers, J., Thomassen, M.C.L.G.D., Nicolaes, G.A.F., Meijers, J., Bouma, B.N., Büller, H.R., Prins, M.H., Tans, G.
(1999) the Lancet, 354, 2036-2040. PMID: 10636369

Partial glycosylation of Asn2181 in human factor V as cause of molecular and functional heterogeneity.
Nicolaes, G.A.F., Villoutreix, B.O., Dahlbäck, B.
(1999) Biochemistry, 38(41), 13584-13591. PMID: 10521265

Acquired APC resistance and oral contraceptives: Differences between two functional tests.
Curvers, J., Thomassen, M.C.L.G.D., Nicolaes, G.A.F., van Oerle, R., Hamulyak, K., Hemker, H.C., Tans, G., Rosing, J.
(1999) British Journal of Haematology, 105(1), 88-94. PMID: 10233368

1997

Regulation of thrombin formation by activated protein C: effect of the FVLeiden mutation.
Tans, G., Nicolaes, G.A.F., Rosing, J.
(1997) Seminars in Hematology, 34(3), 244-255. PMID: 9241709

Human factor Va1 and Va2: Properties in the procoagulant- and anticoagulant pathways.
Hoekema, L, Nicolaes, G.A.F., Tans, G., Hemker, H.C., Rosing, J.
(1997) Biochemistry, 36(11), 3331-3335. PMID: 9116011

Oral Contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second and third generation oral contraceptives.
Rosing, J., Tans, G., Nicolaes, G.A.F., Thomassen M.C.L.G.D., Van Oerle, R., Van der Ploeg, P.M.E.N., Heijnen, P., Hamulyak, K., Hemker, H.C.
(1997) British Journal of Haematology 97, 233-238. PMID: 9136971

Effect of activated protein C on thrombin generation and on the thrombin potential in the plasma of normal and APC resistant individuals.
Nicolaes, G.A.F., Thomassen, M.C.L.G.D., Tans, G., Rosing, J., Hemker, H.C.
(1997) Blood Coagulation & Fibrinolysis 8, 28-38. PMID: 9105635

1996

A prothrombinase-based assay for detection of resistance to activated protein C.
Nicolaes, G.A.F., Thomassen, M.C.L.G.D., van Oerle, R., Hamulyak, K., Hemker, H.C., Tans, G., Rosing, J.
(1996) Thrombosis and Haemostasis 76(3), 404-410. PMID: 8883278

1995

Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor VaR506Q by activated protein C.
Rosing, J., Hoekema, L., Nicolaes, G.A.F., Thomassen, M.C.L.G.D., Hemker, H.C., Varadi, K., Schwarz, H.P., Tans, G.
(1995) Journal of Biological Chemistry 270, 27852-27858. PMID: 7499257

Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C.
Nicolaes, G.A.F., Tans, G., Thomassen, M.C.L.G.D., Hemker, H.C., Pabinger, I., Varadi, K., Schwarz, H.P., Rosing, J.
(1995) Journal of Biological Chemistry 270, 21158-21166.  PMID: 7673148

1994

Activation of human factor V by meizothrombin.
Tans,G., Nicolaes, G.A.F., Thomassen, M.C.L.G.D., Hemker, H.C., van Zonneveld, A-J., Pannekoek, H., Rosing, J.
(1994) Journal of Biological Chemistry 269, 15969-15972. PMID: 8206891

Acylation of porcine pancreatic PLA2 influences penetration and substrate head- group binding, depending on the position of the acylated lysine in the enzyme molecule.
Lugtigheid, R.B., Nicolaes, G.A.F., Veldhuizen, E.J.A., Slotboom, A.J., Verheij, H.M., de Haas, G.H.
(1993) European Journal of Biochemistry 216(2), 519-525. PMID: 8375390