Judith Cosemans

Associate professor

Dr Judith Cosemans holds a master’s degree in Biological Health Sciences with specialisation in molecular biology from Maastricht University. She became fascinated to unravel the role of platelets in arterial thrombosis during her PhD research, which focussed on the dynamic regulation of thrombus stability. After finishing her PhD in 2009, she executed an award-winning postdoc project to develop flow chamber technology as a compatible alternative for experimental animal models of arterial thrombosis.

Dr Cosemans subsequently obtained two personal grants from the Dutch Heart Foundation (2011, 2015) and a Vidi grant from the Netherlands Organisation for Scientific Research (NWO, 2016). These grants facilitate her current research line, which lies on the interface of platelet signalling and vascular biology.

Her team aims to:
• provide novel mechanistic insight into the pathophysiology of thrombosis in the heart and in the brain
• develop better diagnostic tools and novel druggable targets to prevent recurrentthrombotic events

Department of Biochemistry
Universiteitssingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht

  • 2024
    • Lemmens, T. P., Luo, Q., Wielders, S. J. H., Scheijen, J. L. J. M., Al-Nasiry, S., Koenen, R. R., Wenzel, P., & Cosemans, J. M. E. M. (2024). Platelet collagen receptors and their role in modulating platelet adhesion patterns and activation on alternatively processed collagen substrates. Thrombosis Research, 244, Article 109201. https://doi.org/10.1016/j.thromres.2024.109201
    • D'Italia, G., Schroen, B., & Cosemans, J. M. E. M. (2024). Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities. Esc heart failure, Article 15090. https://doi.org/10.1002/ehf2.15090
    • Lemmens, T. P., Bröker, V., Rijpkema, M., Hughes, C. C. W., Schurgers, L. J., & Cosemans, J. M. E. M. (2024). Fundamental considerations for designing endothelialized in vitro models of thrombosis. Thrombosis Research, 236, 179-190. https://doi.org/10.1016/j.thromres.2024.03.004
  • 2023
    • Yakusheva, A., Slater, A., Payrastre, B., Garcia, C., D'Italia, G., Allan, H., Cosemans, J. M. E. M., Harper, M., Gawaz, M., Armstrong, P., Troitiño, S., Trivigno, S. M. G., Naik, U. P., & Senis, Y. A. (2023). Illustrated Abstracts of the 5th EUPLAN International Conference. Research and practice in thrombosis and haemostasis, 7(7), Article 102140. https://doi.org/10.1016/j.rpth.2023.102140
    • Schönichen, C., Montague, S. J., Brouns, S. L. N., Burston, J. J., Cosemans, J. M. E. M., Jurk, K., Kehrel, B. E., Koenen, R. R., Ní Áinle, F., O'Donnell, V. B., Soehnlein, O., Watson, S. P., Kuijpers, M. J. E., Heemskerk, J. W. M., & Nagy, M. (2023). Antagonistic Roles of Human Platelet Integrin αiIbβ3 and Chemokines in Regulating Neutrophil Activation and Fate on Arterial Thrombi under Flow. Arteriosclerosis Thrombosis and Vascular Biology, 43(9), 1700-1712. https://doi.org/10.1161/ATVBAHA.122.318767
    • Josefsson, E. C., Ramstrom, S., Thaler, J., Lordkipanidze, M., Cosemans, J., & COAGAPO Study Group (2023). Consensus report on markers to distinguish procoagulant platelets from apoptotic platelets: communication from the Scientific and Standardization Committee of the ISTH. Journal of Thrombosis and Haemostasis, 21(8), 2291-2299. https://doi.org/10.1016/j.jtha.2023.05.001
  • 2022
    • Karel, M. F. A., Roosen, M. G. C. H., Tullemans, B. M. E., Zhang, C. E., Staals, J., Cosemans, J. M. E. M., & Koenen, R. R. (2022). Characterization of cerebral small vessel disease by neutrophil and platelet activation markers using artificial intelligence. Journal of Neuroimmunology, 367, Article 577863. https://doi.org/10.1016/j.jneuroim.2022.577863
    • Lemmens, T. P., Coenen, D. M., Swieringa, F., Niessen, I. C. L., Coort, S. L. M., Koenen, R. R., Kutmon, M., & Cosemans, J. M. E. M. (2022). Finding the "switch" in platelet activation: prediction of key mediators involved in reversal of platelet activation using a novel network biology approach. Journal of Proteomics, 261, Article 104577. https://doi.org/10.1016/j.jprot.2022.104577
    • Karel, M. F. A., Tullemans, B. M. E., D'Italia, G., Lemmens, T. P., Claushuis, T. A. M., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2022). Corrigendum to "The effect of Bruton's tyrosine kinase inhibitor ibrutinib on atherothrombus formation under stenotic flow conditions" [Thromb. Res. 212 (2022) 72-80]. Thrombosis Research, 213, 113-113. https://doi.org/10.1016/j.thromres.2022.03.012
    • Karel, M. F. A., Tullemans, B. M. E., D'Italia, G., Lemmens, T. P., Claushuis, T. A. M., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2022). The effect of Bruton's tyrosine kinase inhibitor ibrutinib on atherothrombus formation under stenotic flow conditions. Thrombosis Research, 212, 72-80. https://doi.org/10.1016/j.thromres.2022.02.020
    • Cosemans, J. M. E. M. (2022). Platelet-derived MMP-2 in the prevention of plaque formation: how many strokes is par?European Heart Journal, 43(6), 515–517. https://doi.org/10.1093/eurheartj/ehab665
    • Karel, M. F. A., Lemmens, T. P., Tullemans, B. M. E., Wielders, S. J. H., Gubbins, E., van Beurden, D., van Rijt, S., & Cosemans, J. M. E. M. (2022). Characterization of Atherosclerotic Plaque Coating for Thrombosis Microfluidics Assays. Cellular and Molecular Bioengineering, 15(1), 55-65. https://doi.org/10.1007/s12195-021-00713-9
  • 2021
    • Heinzmann, A. C. A., Coenen, D. M., Vajen, T., Cosemans, J. M. E. M., & Koenen, R. R. (2021). Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets. TH open : companion journal to thrombosis and haemostasis, 5(4), e533-e542. https://doi.org/10.1055/a-1682-3415
    • Coenen, D. M., Heinzmann, A. C. A., Oggero, S., Albers, H. J., Nagy, M., Hague, P., Kuijpers, M. J. E., Vanderwinden, J. M., van der Meer, A. D., Perretti, M., Koenen, R. R., & Cosemans, J. M. E. M. (2021). Inhibition of Phosphodiesterase 3A by Cilostazol Dampens Proinflammatory Platelet Functions. Cells, 10(8), Article 1998. https://doi.org/10.3390/cells10081998
    • Mangin, P. H., Neeves, K. B., Lam, W. A., Cosemans, J. M. E. M., Korin, N., Kerrigan, S. W., Panteleev, M. A., & Subcommittee on Biorheology (2021). In vitro flow-based assay: From simple toward more sophisticated models for mimicking hemostasis and thrombosis. Journal of Thrombosis and Haemostasis, 19(2), 582-587. https://doi.org/10.1111/jth.15143
    • Coenen, D. M., Heinzmann, A. C. A., Karel, M. F. A., Cosemans, J. M. E. M., & Koenen, R. R. (2021). The multifaceted contribution of platelets in the emergence and aftermath of acute cardiovascular events. Atherosclerosis, 319, 132-141. https://doi.org/10.1016/j.atherosclerosis.2020.12.017
    • Panteleev, M. A., Korin, N., Reesink, K. D., Bark, D. L., Cosemans, J. M. E. M., Gardiner, E. E., & Mangin, P. H. (2021). Wall shear rates in human and mouse arteries: Standardization of hemodynamics for in vitro blood flow assays: Communication from the ISTH SSC subcommittee on biorheology. Journal of Thrombosis and Haemostasis, 19(2), 588-595. https://doi.org/10.1111/jth.15174
    • Tullemans, B., Karel, M., Léopold, V., ten Brink, M. S., Baaten, C., Maas, S. L., de Vos, A. F., Eble, J. A., Nijziel, M. R., van der Vorst, E., Cosemans, J., Heemskerk, J., Claushuis, T. A. M., & Kuijpers, M. (2021). Comparison of inhibitory effects of irreversible and reversible Btk inhibitors on platelet function. eJHaem, 2(4), 685–699. https://doi.org/10.1002/jha2.269
  • 2020
    • Mastenbroek, T. G., Karel, M. F. A., Nagy, M., Chayoua, W., Korsten, E. I. J., Coenen, D. M., Debets, J., Konings, J., Brouns, A. E., Leenders, P. J. A., van Essen, H., van Oerle, R., Heitmeier, S., Spronk, H. M., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2020). Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery. Scientific Reports, 10(1), Article 19360. https://doi.org/10.1038/s41598-020-76377-8
    • Heinzmann, A. C. A., Karel, M. F. A., Coenen, D. M., Vajen, T., Meulendijks, N. M. M., Nagy, M., Suylen, D. P. L., Cosemans, J. M. E. M., Heemskerk, J. W. M., Hackeng, T. M., & Koenen, R. R. (2020). Complementary roles of platelet αIIbβ3 integrin, phosphatidylserine exposure and cytoskeletal rearrangement in the release of extracellular vesicles. Atherosclerosis, 310, 17-25. https://doi.org/10.1016/j.atherosclerosis.2020.07.015
    • Tilburg, J., Coenen, D. M., Zirka, G., Dolleman, S., van Oeveren-Rietdijk, A. M., Karel, M. F. A., de Boer, H. C., Cosemans, J. M. E. M., Versteeg, H. H., Morange, P. E., van Vlijmen, B. J. M., Maracle, C. X., & Thomas, G. M. (2020). SLC44A2 deficient mice have a reduced response in stenosis but not in hypercoagulability driven venous thrombosis. Journal of Thrombosis and Haemostasis, 18(7), 1714-1727. https://doi.org/10.1111/jth.14835
    • Sternkopf, M., Nagy, M., Baaten, C. C. F. M. J., Kuijpers, M. J. E., Tullemans, B. M. E., Wirth, J., Theelen, W., Mastenbroek, T. G., Lehrke, M., Winnerling, B., Baerts, L., Marx, N., De Meester, I., Doring, Y., Cosemans, J. M. E. M., Daiber, A., Steven, S., Jankowski, J., Heemskerk, J. W. M., & Noels, H. (2020). Native, Intact Glucagon-Like Peptide 1 Is a Natural Suppressor of Thrombus Growth Under Physiological Flow Conditions. Arteriosclerosis Thrombosis and Vascular Biology, 40(3), E65-E77. https://doi.org/10.1161/atvbaha.119.313645
    • Karel, M. F. A., Hechler, B., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2020). Atherosclerotic plaque injury-mediated murine thrombosis models: advantages and limitations. Platelets, 31(4), 439-446. https://doi.org/10.1080/09537104.2019.1708884
  • 2019
    • Van Kuijk, K., Theelen, T., Demandt, J., Marsch, E., Gijbels, M., Jin, H., Reutelingsperger, C., Cosemans, J., Schurgers, L., Carmeliet, P., Biessen, E., Daemen, M., & Sluimer, J. (2019). MYELOID PHD2 KNOCKDOWN DRIVES MACROPHAGE APOPTOSIS AND PARACRINE FIBROBLAST/SMOOTH MUSCLE CELL COLLAGEN SECRETION LEADING TO ATHEROSCLEROTIC PLAQUE FIBROSIS. Atherosclerosis, 287, E10-E10. https://doi.org/10.1016/j.atherosclerosis.2019.06.027
    • Govers-Riemslag, J. W. P., Konings, J., Cosemans, J. M. E. M., van Geffen, J. P., de Laat, B., Heemskerk, J. W. M., Dargaud, Y., & Ten Cate, H. (2019). Impact of Deficiency of Intrinsic Coagulation Factors XI and XII on Ex Vivo Thrombus Formation and Clot Lysis. TH open : companion journal to thrombosis and haemostasis, 3(3), e273-e285. https://doi.org/10.1055/s-0039-1693485
  • 2018
    • Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., & Heemskerk, J. W. M. (2018). A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding. Blood, 132(24), E35-E46. https://doi.org/10.1182/blood-2018-02-831982
    • Thomassen, S., Mastenbroek, T. G., Swieringa, F., Winckers, K., Feijge, M. A. H., Schrijver, R., Cosemans, J. M. E. M., Maroney, S. A., Mast, A. E., Hackeng, T. M., & Heemskerk, J. W. M. (2018). Suppressive Role of Tissue Factor Pathway Inhibitor-alpha in Platelet-Dependent Fibrin Formation under Flow Is Restricted to Low Procoagulant Strength. Thrombosis and Haemostasis, 118(3), 502-513. https://doi.org/10.1055/s-0038-1627453
    • Nagy, M., Mastenbroek, T. G., Mattheij, N. J. A., de Witt, S., Clemetson, K. J., Kirschner, J., Schulz, A. S., Vraetz, T., Speckmann, C., Braun, A., Cosemans, J. M. E. M., Zieger, B., & Heemskerk, J. W. M. (2018). Variable impairment of platelet functions in patients with severe, genetically linked immune deficiencies. Haematologica-the Hematology Journal, 103(3), 540-549. https://doi.org/10.3324/haematol.2017.176974
    • Cosemans, J. M. E. M. (2018). At the MERcy of platelet primers. Journal of Thrombosis and Haemostasis, 16(2), 349-351. https://doi.org/10.1111/jth.13915
  • 2017
    • Coenen, D. M., Mastenbroek, T. G., & Cosemans, J. M. E. M. (2017). Platelet interaction with activated endothelium: mechanistic insights from microfluidics. Blood, 130(26), 2819-2828. https://doi.org/10.1182/blood-2017-04-780825
  • 2016
    • Solari, F. A., Mattheij, N. J. A., Burkhart, J. M., Swieringa, F., Collins, P. W., Cosemans, J. M. E. M., Sickmann, A., Heemskerk, J. W. M., & Zahedi, R. P. (2016). Combined Quantification of the Global Proteome, Phosphoproteome, and Proteolytic Cleavage to Characterize Altered Platelet Functions in the Human Scott Syndrome. Molecular & Cellular Proteomics, 15(10), 3154-3169. https://doi.org/10.1074/mcp.M116.060368
    • Mattheij, N. J. A., Swieringa, F., Mastenbroek, T. G., Berny-Lang, M. A., May, F., Baaten, C. C. F. M. J., van der Meijden, P. E. J., Henskens, Y. M. C., Beckers, E. A. M., Suylen, D. P. L., Nolte, M. W., Hackeng, T. M., McCarty, O. J. T., Heemskerk, J. W. M., & Cosemans, J. M. E. M. (2016). Coated platelets function in platelet-dependent fibrin formation via integrin alpha(IIb)beta(3) and transglutaminase factor XIII. Haematologica-the Hematology Journal, 101(4), 427-436. https://doi.org/10.3324/haematol.2015.131441
    • Swieringa, F., Baaten, C. C. F. M. J., Verdoold, R., Mastenbroek, T. G., Rijnveld, N., van der Laan, K. O., Breel, E. J., Collins, P. W., Lance, M. D., Henskens, Y. M. C., Cosemans, J. M. E. M., Heemskerk, J. W. M., & van der Meijden, P. E. J. (2016). Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow. Arteriosclerosis Thrombosis and Vascular Biology, 36(4), 692-699. https://doi.org/10.1161/ATVBAHA.115.306537
    • McCarty, O. J. T., Ku, D., Sugimoto, M., King, M. R., Cosemans, J. M. E. M., & Neeves, K. B. (2016). Dimensional analysis and scaling relevant to flow models of thrombus formation: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis, 14(3), 619-622. https://doi.org/10.1111/jth.13241
    • Mattheij, N. J. A., Braun, A., van Kruchten, R., Castoldi, E., Pircher, J., Baaten, C. C. F. M. J., Wuelling, M., Kuijpers, M. J. E., Koehler, R., Poole, A. W., Schreiber, R., Vortkamp, A., Collins, P. W., Nieswandt, B., Kunzelmann, K., Cosemans, J. M. E. M., & Heemskerk, J. W. M. (2016). Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage. Faseb Journal, 30(2), 727-737. https://doi.org/10.1096/fj.15-280446
    • Mattheij, N., Braun, A., van Kruchten, R., Castoldi, E., PIRCHER, J., Baaten, C., WÜLLING, M., Kuijpers, M., KÖHLER, R., POOLE, A. W., Schreiber, R., VORTKAMP, A., COLLINS, P. W., Nieswandt, B., KUNZELMANN, K., Cosemans, J., & Heemskerk, J. (2016). Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling and swelling. Nederlands tijdschrift voor klinische chemie en laboratoriumgeneeskunde, 41(3), 207-208. https://www.nvkc.nl/sites/default/files/NTKC/Mattheij.pdf
  • 2015
    • Mastenbroek, T. G., Feijge, M. A. H., Kremers, R. M. W., van den Bosch, M. T. J., Swieringa, F., De Groef, L., Moons, L., Bennett, C., Ghevaert, C., Johnson, J. L., van der Meijden, P. E. J., & Cosemans, J. M. E. M. (2015). Platelet-Associated Matrix Metalloproteinases Regulate Thrombus Formation and Exert Local Collagenolytic Activity. Arteriosclerosis Thrombosis and Vascular Biology, 35(12), 2554-2561. https://doi.org/10.1161/ATVBAHA.115.306153
    • Agbani, E. O., van den Bosch, M. T. J., Brown, E., Williams, C. M., Mattheij, N. J. A., Cosemans, J. M. E. M., Collins, P. W., Heemskerk, J. W. M., Hers, I., & Poole, A. W. (2015). Coordinated Membrane Ballooning and Procoagulant Spreading in Human Platelets. Circulation, 132(15), 1414-1424. https://doi.org/10.1161/CIRCULATIONAHA.114.015036
    • Mastenbroek, T. G., Van Geffen, J. P., Heemskerk, J. W. M., & Cosemans, J. M. E. M. (2015). Acute and persistent platelet and coagulant activities in atherothrombosis. Journal of Thrombosis and Haemostasis, 13(S1), S272-S280. https://doi.org/10.1111/jth.12972
    • Kuijpers, M. J. E., Mattheij, N. J. A., Cipolla, L., van Geffen, J. P., Lawrence, T., Donners, M. M. P. C., Boon, L., Lievens, D., Torti, M., Noels, H., Gerdes, N., Cosemans, J. M. E. M., Lutgens, E., & Heemskerk, J. W. M. (2015). Platelet CD40L Modulates Thrombus Growth Via Phosphatidylinositol 3-Kinase beta, and Not Via CD40 and I kappa B Kinase alpha. Arteriosclerosis Thrombosis and Vascular Biology, 35(6), 1374-1381. https://doi.org/10.1161/ATVBAHA.114.305127
    • van Geffen, J. P., Kleinegris, M.-C., Verdoold, R., Baaten, C. C. F. M. J., Cosemans, J. M. E. M., Clemetson, K. J., ten Cate, H., Roest, M., de Laat, B., & Heemskerk, J. W. M. (2015). Normal Platelet Activation Profile in Patients with Peripheral Arterial Disease on Aspirin. Thrombosis Research, 135(3), 513-520. https://doi.org/10.1016/j.thromres.2014.12.029
    • Karshovska, E., Zhao, Z., Blanchet, X., Schmitt, M. M. N., Bidzhekov, K., Soehnlein, O., von Hundelshausen, P., Mattheij, N. J., Cosemans, J. M. E. M., Megens, R. T. A., Koeppel, T. A., Schober, A., Hackeng, T. M., Weber, C., & Koenen, R. R. (2015). Hyperreactivity of Junctional Adhesion Molecule A-Deficient Platelets Accelerates Atherosclerosis in Hyperlipidemic Mice. Circulation Research, 116(4), 587-599. https://doi.org/10.1161/CIRCRESAHA.116.304035
  • 2014
    • Beinsberger, J., Heemskerk, J. W. M., & Cosemans, J. M. E. M. (2014). Chronic arthritis and cardiovascular disease: Altered blood parameters give rise to a prothrombotic propensity. Seminars in Arthritis and Rheumatism, 44(3), 345-352. https://doi.org/10.1016/j.semarthrit.2014.06.006
    • Kuijpers, M. J. E., van der Meijden, P. E. J., Feijge, M. A. H., Mattheij, N. J. A., May, F., Govers-Riemslag, J., Meijers, J. C. M., Heemskerk, J. W. M., Renne, T., & Cosemans, J. M. E. M. (2014). Factor XII Regulates the Pathological Process of Thrombus Formation on Ruptured Plaques. Arteriosclerosis Thrombosis and Vascular Biology, 34(8), 1674–1680. https://doi.org/10.1161/ATVBAHA.114.303315
    • de Witt, S. M., Swieringa, F., Cavill, R., Lamers, M. M., van Kruchten, R., Mastenbroek, T., Baaten, C., Coort, S., Pugh, N., Schulz, A., Scharrer, I., Jurk, K., Zieger, B., Clemetson, K. J., Farndale, R. W., Heemskerk, J. W., & Cosemans, J. M. (2014). Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nature Communications, 5, Article 4257. https://doi.org/10.1038/ncomms5257
    • Kuijpers, M. J. E., de Witt, S., Nergiz-Unal, R., van Kruchten, R., Korporaal, S. J. A., Verhamme, P., Febbraio, M., Tjwa, M., Voshol, P. J., Hoylaerts, M. F., Cosemans, J. M. E. M., & Heemskerk, J. W. M. (2014). Supporting Roles of Platelet Thrombospondin-1 and CD36 in Thrombus Formation on Collagen. Arteriosclerosis Thrombosis and Vascular Biology, 34(6), 1187-1192. https://doi.org/10.1161/ATVBAHA.113.302917
    • de Witt, S. M., Verdoold, R., Cosemans, J. M. E. M., & Heemskerk, J. W. M. (2014). Insights into platelet-based control of coagulation. Thrombosis Research, 133(SUPPL. 2), S139-S148. https://doi.org/10.1016/S0049-3848(14)50024-2
    • Muenzer, P., Borst, O., Walker, B., Schmid, E., Feijge, M. A. H., Cosemans, J. M. E. M., Chatterjee, M., Schmidt, E.-M., Schmidt, S., Towhid, S. T., Leibrock, C., Elvers, M., Schaller, M., Seizer, P., Ferlinz, K., May, A. E., Gulbins, E., Heemskerk, J. W. M., Gawaz, M., & Lang, F. (2014). Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation. Arteriosclerosis Thrombosis and Vascular Biology, 34(1), 61–71. https://doi.org/10.1161/ATVBAHA.112.300210
  • 2013
    • Cosemans, J. M. E. M., Angelillo-Scherrer, A., Mattheij, N. J. A., & Heemskerk, J. W. M. (2013). The effects of arterial flow on platelet activation, thrombus growth, and stabilization. Cardiovascular Research, 99(2), 342-352. https://doi.org/10.1093/cvr/cvt110
    • Mattheij, N. J. A., Gilio, K., van Kruchten, R., Jobe, S. M., Wieschhaus, A. J., Chishti, A. H., Collins, P., Heemskerk, J. W. M., & Cosemans, J. M. E. M. (2013). Dual Mechanism of Integrin alpha(IIb)beta(3) Closure in Procoagulant Platelets. Journal of Biological Chemistry, 288(19), 13325-13336. https://doi.org/10.1074/jbc.M112.428359