Leon de Windt

Professor

Prof. Leon de Windt obtained a Master’s degree in Molecular Biology at Utrecht University in 1994, and a PhD in Cardiovascular Physiology at Maastricht University in 1999. Following a post-doctoral residence at the Howard Hughes Medical Institute of Jeffery Molkentin in Cincinnati OH, USA, he became group leader at the Hubrecht Institute in Utrecht. As of 2010, he was appointed as Professor of Molecular Cardiovascular Biology at Maastricht University and chairs a team including one associate professor, one tenure-track assistant professor and 15 PhD students. Leon is the recipient of several Awards, including a 2008 Fondation Leducq Transatlantic Network of Excellence; the 2012 Outstanding Achievement Award of the ESC Council for Basic Cardiovascular Science and the 2012 Galenus Research Prize. In 2013, he received an ERC Consolidator Grant from the European Research Council (ERC) and became coordinator of Dutch Heart Foundation funded CVON-ARENA consortium to support his work. He received the Veni (2001), Vidi (2007) and Vici (2017) career development awards from the Netherlands Organisation of Scientific Research (NWO). In 2018, he became coordinator of the Dutch Heart Foundation funded DCVA-ARENA-PRIME consortium aimed to tackle inherited heart diseases. Since 2019 he coordinates the Marie Skłodowska Curie Actions Innovative Training Network 'TRAIN-HEART' (www.train-heart.eu).

His research focusess on the function of non-coding RNAs as epigenetic regulators of cardiac gene expression using genetic manipulation in (iPS-derived) cardiomyocytes and mouse models. More recently, his team exploits their academic findings towards rational therapy development for various genetic and acquired forms of heart failure in the Dutch spin-off company Mirabilis Therapeutics BV that he co-founded in 2015. The research is performed in close collaboration with chemists, life scientists, and clinicians, and often executed within public-private partnerships. Many alumni from his group have successfully started their own research laboratories, fulfill executive industrial functions or became clinician-researchers as the future generation of leaders in medicine (see: www.dewindtlab.com).

 

Department of Cardiology
Department of Molecular Biology and RNA Technology 
Universiteitsingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht

  • 2016
    • Vegter, E. L., van der Meer, P., de Windt, L. J., Pinto, Y. M., & Voors, A. A. (2016). MicroRNAs in heart failure: from biomarker to target for therapy. European journal of heart failure, 18(5), 457-468. https://doi.org/10.1002/ejhf.495
    • Peters, T., Beijnsberger, S., Beqqali, A., Bitsch, N., Nakagawa, S., Prasanth, K. V., de Windt, L. J., van Oort, R. J., Heymans, S., & Schroen, B. (2016). Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice. PLOS ONE, 11(2), Article e0150236. https://doi.org/10.1371/journal.pone.0150236
    • Viereck, J., Kumarswamy, R., Foinquinos, A., Xiao, K., Avramopoulos, P., Kunz, M., Dittrich, M., Maetzig, T., Zimmer, K., Remke, J., Just, A., Fendrich, J., Scherf, K., Bolesani, E., Schambach, A., Weidemann, F., Zweigerdt, R., de Windt, L. J., Engelhardt, S., ... Thum, T. (2016). Long noncoding RNA Chast promotes cardiac remodeling. Science Translational Medicine, 8(326), Article 326ra22. https://doi.org/10.1126/scitranslmed.aaf1475
    • Duygu, B., de Windt, L. J., & Da Costa Martins, P. (2016). Targeting microRNAs in heart failure. Trends in Cardiovascular Medicine, 26(2), 99-110. https://doi.org/10.1016/j.tcm.2015.05.008
  • 2015
    • Philippen, L. E., Dirkx, E., Wit, J. B. M., Burggraaf, K., de Windt, L. J., & Martins, P. A. D. C. (2015). Antisense MicroRNA Therapeutics in Cardiovascular Disease: Quo Vadis?Molecular Therapy, 23(12), 1810-1818. https://doi.org/10.1038/mt.2015.133
    • Calore, M., De Windt, L. J., & Rampazzo, A. (2015). Genetics meets epigenetics: Genetic variants that modulate noncoding RNA in cardiovascular diseases. Journal of Molecular and Cellular Cardiology, 89, 27-34. https://doi.org/10.1016/j.yjmcc.2015.10.028
    • Philippen, L. E., Dirkx, E., da Costa-Martins, P. A., & De Windt, L. J. (2015). Non-coding RNA in control of gene regulatory programs in cardiac development and disease. Journal of Molecular and Cellular Cardiology, 89(Pt A), 51-8. https://doi.org/10.1016/j.yjmcc.2015.03.014
    • De Windt, L. J., & Thum, T. (2015). State-of-the-art on non-coding RNA bioinformatics, diagnostics and therapeutics in cardiovascular diseases: Preface to SI Non-coding RNAs in cardiovascular disease. Journal of Molecular and Cellular Cardiology, 89(Pt A), 1-2. https://doi.org/10.1016/j.yjmcc.2015.11.021
    • Calore, M., & De Windt, L. J. (2015). Longing for Naiades in Heart Failure. Journal of the American College of Cardiology, 66(18), 2016-2018. https://doi.org/10.1016/j.jacc.2015.08.868
    • d'Avenia, M., Citro, R., De Marco, M., Veronese, A., Rosati, A., Visone, R., Leptidis, S., Philippen, L., Vitale, G., Cavallo, A., Silverio, A., Prota, C., Gravina, P., De Cola, A., Carletti, E., Coppola, G., Gallo, S., Provenza, G., Bossone, E., ... De laurenzi, V. (2015). A novel miR-371a-5p-mediated pathway, leading to BAG3 upregulation in cardiomyocytes in response to epinephrine, is lost in Takotsubo cardiomyopathy. Cell Death & Disease, 6, Article e1948. https://doi.org/10.1038/cddis.2015.280
    • Cannon, M. V., Sillje, H. H. W., Sijbesma, J. W. A., Vreeswijk-Baudoin, I., Ciapaite, J., van der Sluis, B., van Deursen, J., Silva, G. J. J., de Windt, L. J., Gustafsson, J.-A., van der Harst, P., van Gilst, W. H., & de Boer, R. A. (2015). Cardiac LXR protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Molecular Medicine, 7(9), 1229-1243. https://doi.org/10.15252/emmm.201404669
    • el Azzouzi, H., Leptidis, S., Doevendans, P. A., & De Windt, L. J. (2015). HypoxamiRs: regulators of cardiac hypoxia and energy metabolism. Trends in Endocrinology and Metabolism, 26(9), 502-508. https://doi.org/10.1016/j.tem.2015.06.008
  • 2014
    • Martins, P. A. D. C., Leptidis, S., & De Windt, L. J. (2014). Nuclear Calcium Transients Hermes Propylaios in the Heart. Circulation, 130(3), 221-223. https://doi.org/10.1161/CIRCULATIONAHA.114.010675
    • Leite-Moreira, A. F., Lourenco, A. P., Balligand, J.-L., Bauersachs, J., Clerk, A., De Windt, L. J., Heymans, S., Hilfiker-Kleiner, D., Hirsch, E., Iaccarino, G., Kaminski, K. A., Knoell, R., Mayr, M., Tarone, G., Thum, T., & Tocchetti, C. G. (2014). ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models. European journal of heart failure, 16(5), 509-518. https://doi.org/10.1002/ejhf.66
    • Tarone, G., Balligand, J.-L., Bauersachs, J., Clerk, A., De Windt, L., Heymans, S., Hilfiker-Kleiner, D., Hirsch, E., Iaccarino, G., Knoell, R., Leite-Moreira, A. F., Lourenco, A. P., Mayr, M., Thum, T., & Tocchetti, C. G. (2014). Targeting myocardial remodelling to develop novel therapies for heart failure A position paper from the Working Group on Myocardial Function of the European Society of Cardiology. European journal of heart failure, 16(5), 494-508. https://doi.org/10.1002/ejhf.62
    • Poels, E. M., Bitsch, N., Slenter, J. M., Kooi, M. E., de Theije, C. C., De Windt, L. J., van Empel, V. P., & da Costa Martins, P. A. (2014). Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice. PLOS ONE, 9(4), Article 92983. https://doi.org/10.1371/journal.pone.0092983
    • Roncarati, R., Anselmi, C. V., Losi, M. A., Papa, L., Cavarretta, E., Martins, P. D. C., Contaldi, C., Jotti, G. S., Franzone, A., Galastri, L., Latronico, M. V. G., Imbriaco, M., Esposito, G., De Windt, L., Betocchi, S., & Condorelli, G. (2014). Circulating miR-29a, Among Other Up-Regulated MicroRNAs, Is the Only Biomarker for Both Hypertrophy and Fibrosis in Patients With Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology, 63(9), 920-927. https://doi.org/10.1016/j.jacc.2013.09.041
  • 2013
    • Dirkx, E., da Costa Martins, P. A., & De Windt, L. J. (2013). Regulation of fetal gene expression in heart failure. Biochimica et Biophysica Acta-Molecular Basis of Disease, 1832(12), 2414-2424. https://doi.org/10.1016/j.bbadis.2013.07.023
    • Dirkx, E., Gladka, M. M., Philippen, L. E., Armand, A.-S., Kinet, V., Leptidis, S., el Azzouzi, H., Salic, K., Bourajjaj, M., da Silva, G. J. J., Olieslagers, S., van der Nagel, R., de Weger, R., Bitsch, N., Kisters, N., Seyen, S., Morikawa, Y., Chanoine, C., Heymans, S., ... De Windt, L. J. (2013). Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nature Cell Biology, 15(11), 1282-1293. https://doi.org/10.1038/ncb2866
    • Tritsch, E., Mallat, Y., Lefebvre, F., Diguet, N., Escoubet, B., Blanc, J., De Windt, L. J., Catalucci, D., Vandecasteele, G., Li, Z., & Mericskay, M. (2013). An SRF/miR-1 axis regulates NCX1 and Annexin A5 protein levels in the normal and failing heart. Cardiovascular Research, 98(3), 372-380. https://doi.org/10.1093/cvr/cvt042
    • Leptidis, S., el Azzouzi, H., Lok, S. I., de Weger, R., Olieslagers, S., Kisters, N., Silva, G. J., Heymans, S., Cuppen, E., Berezikov, E., De Windt, L. J., & Martins, P. D. C. (2013). A Deep Sequencing Approach to Uncover the miRNOME in the Human Heart. PLOS ONE, 8(2), Article e57800. https://doi.org/10.1371/journal.pone.0057800
  • 2012
    • van Empel, V. P. M., De Windt, L. J., & Martins, P. A. D. C. (2012). Circulating miRNAs: Reflecting or Affecting Cardiovascular Disease?Current Hypertension Reports, 14(6), 498-509. https://doi.org/10.1007/s11906-012-0310-7
    • Bourgonje, V. J. A., Schoenmakers, M., Beekman, J. D. M., van der Nagel, R., Houtman, M. J. C., Miedema, L. F., Antoons, G., Sipido, K., de Windt, L. J., van Veen, T. A. B., & Vos, M. A. (2012). Relevance of calmodulin/CaMKII activation for arrhythmogenesis in the AV block dog. Heart Rhythm, 9(11), 1875-1883.e2. https://doi.org/10.1016/j.hrthm.2012.07.023
    • el Azzouzi, H., Leptidis, S., Bourajjaj, M., van Bilsen, M., Martins, P. A. D. C., & De Windt, L. J. (2012). MEK1 Inhibits Cardiac PPAR alpha Activity by Direct Interaction and Prevents Its Nuclear Localization. PLOS ONE, 7(6), Article e36799. https://doi.org/10.1371/journal.pone.0036799
    • Salic, K., & De Windt, L. J. (2012). MicroRNAs as Biomarkers for Myocardial Infarction. Current Atherosclerosis Reports, 14(3), 193-200. https://doi.org/10.1007/s11883-012-0238-z
    • Martins, P. A. D. C., & De Windt, L. J. (2012). MicroRNAs in control of cardiac hypertrophy. Cardiovascular Research, 93(4), 563-572. https://doi.org/10.1093/cvr/cvs013
    • Heijman, J., Spätjens, R. L. H., Seyen, S. R. M., Lentink, V., Kuijpers, H. J. H., Boulet, I. R., de Windt, L. J., David, M., & Volders, P. G. A. (2012). Dominant-Negative Control of cAMP-Dependent I-Ks Upregulation in Human Long-QT Syndrome Type 1. Circulation Research, 110(2), 211–219. https://doi.org/10.1161/CIRCRESAHA.111.249482
    • Gladka, M. M., Martins, P. A. D. C., & de Windt, L. J. (2012). Small changes can make a big difference - MicroRNA regulation of cardiac hypertrophy. Journal of Molecular and Cellular Cardiology, 52(1), 74-82. https://doi.org/10.1016/j.yjmcc.2011.09.015
  • 2011
    • Bartelds, B., Borgdorff, M. A., Smit-van Oosten, A., Takens, J., Boersma, B., Nederhoff, M. G., Elzenga, N. J., van Gilst, W. H., De Windt, L. J., & Berger, R. M. F. (2011). Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load. European journal of heart failure, 13(12), 1275-1282. https://doi.org/10.1093/eurjhf/hfr134
    • Armand, A.-S., Laziz, I., Djeghloul, D., Lecolle, S., Bertrand, A. T., Biondi, O., De Windt, L. J., & Chanoine, C. (2011). Apoptosis-Inducing Factor Regulates Skeletal Muscle Progenitor Cell Number and Muscle Phenotype. PLOS ONE, 6(11), 15. https://doi.org/10.1371/journal.pone.0027283
    • el Azzouzi, H., Leptidis, S., Bourajjaj, M., Armand, A.-S., van der Nagel, R., van Bilsen, M., Martins, P. A. D. C., & De Windt, L. J. (2011). Peroxisome Proliferator-activated Receptor (PPAR) Gene Profiling Uncovers Insulin-like Growth Factor-1 as a PPAR alpha Target Gene in Cardioprotection. Journal of Biological Chemistry, 286(16), 14598-14607. https://doi.org/10.1074/jbc.M111.220525
  • 2010
    • Martins, P. A. D. C., Salic, K., Gladka, M. M., Armand, A.-S., Leptidis, S., el Azzouzit, H., Hansen, A., Coenen-de Roo, C. J., Bierhuizen, M. F. A., van der Nagel, R., van Kuik, J., de Weger, R. A., de Bruin, A., Condorelli, G., Arbones, M. L., Eschenhagen, T., & De Windt, L. J. (2010). MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nature Cell Biology, 12(12), 1220-U231. https://doi.org/10.1038/ncb2126
    • den Hengst, W. A., Gielis, J. F., Lin, J. Y., Van Schil, P. E. Y., De Windt, L. J., & Moens, A. L. (2010). Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. American Journal of Physiology-heart and Circulatory Physiology, 299(5), H1283-H1299. https://doi.org/10.1152/ajpheart.00251.2010
    • Martins, P. A. D. C., Leptidis, S., Salic, K., & De Windt, L. J. (2010). MicroRNA Regulation in Cardiovascular Disease. Current Drug Targets, 11(8), 900-906. https://doi.org/10.2174/138945010791591322
    • Tijsen, A. J., Creemers, E. E., Moerland, P. D., de Windt, L. J., van der Wal, A. C., Kok, W. E., & Pinto, Y. M. (2010). MiR423-5p As a Circulating Biomarker for Heart Failure. Circulation Research, 106(6), 1035-U63. https://doi.org/10.1161/CIRCRESAHA.110.218297
    • van Oort, R. J., Respress, J. L., Li, N., Reynolds, C., De Almeida, A. C., Skapura, D. G., De Windt, L. J., & Wehrens, X. H. T. (2010). Accelerated Development of Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction in an RyR2-R176Q Knockin Mouse Model. Hypertension, 55(4), 932-U216. https://doi.org/10.1161/HYPERTENSIONAHA.109.146449
    • van Rooij, E., Fielitz, J., Sutherland, L. B., Thijssen, V. L., Crijns, H. J., Dimaio, M. J., Shelton, J., De Windt, L. J., Hill, J. A., & Olson, E. N. (2010). Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor. Circulation Research, 106(1), 155-U315. https://doi.org/10.1161/CIRCRESAHA.109.207084
    • el Azzouzi, H., van Oort, R. J., van der Nagel, R., Sluiter, W., Bergmann, M. W., & De Windt, L. J. (2010). MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload. European journal of heart failure, 12(1), 4-12. https://doi.org/10.1093/eurjhf/hfp165
  • 2006
    • van Empel, V. P. M., Bertrand, A. T., van Oort, R. J., van der Nagel, R., Engelen, M. P. K. J., van Rijen, H. V., Doevendans, P. A. F. M., Crijns, H. J. G. M., Ackerman, S. L., Sluiter, W., & de Windt, L. J. (2006). EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant. Journal of the American College of Cardiology, 48(4), 824-832. https://doi.org/10.1016/j.jacc.2006.02.075