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

  • 2020
    • Kesidou, D., Martins, P. A. D. C., de Windt, L. J., Brittan, M., Beqqali, A., & Baker, A. H. (2020). Extracellular Vesicle miRNAs in the Promotion of Cardiac Neovascularisation. Frontiers in physiology, 11, [579892]. https://doi.org/10.3389/fphys.2020.579892
    • Bar, C., Chatterjee, S., Pires, I. F., Rodrigues, P., Sluijter, J. P. G., Boon, R. A., Nevado, R. M., Andres, V., Sansonetti, M., de Windt, L., Ciccarelli, M., Hamdani, N., Heymans, S., Videira, R. F., Tocchetti, C. G., Giacca, M., Zacchigna, S., Engelhardt, S., Dimmeler, S., ... Thum, T. (2020). Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart. Cardiovascular Research, 116(11), 1805-1819. https://doi.org/10.1093/cvr/cvaa195
    • De Majo, F., Hegenbarth, J-C., Ruehle, F., Baer, C., Thum, T., de Boer, M., Duncker, D. J., Schroen, B., Armand, A-S., Stoll, M., & De Windt, L. J. (2020). Dichotomy between the transcriptomic landscape of naturally versus accelerated aged murine hearts. Scientific Reports, 10(1), [8136]. https://doi.org/10.1038/s41598-020-65115-9
    • Vonhoegen, I. G. C., el Azzouzi, H., Olieslagers, S., Vasilevich, A., de Boer, J., Tinahones, F. J., Martins, P. A. D. C., de Windt, L. J., & Murri, M. (2020). MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1. Cells, 9(4), [1056]. https://doi.org/10.3390/cells9041056
  • 2019
    • Triposkiadis, F., Butler, J., Abboud, F. M., Armstrong, P. W., Adamopoulos, S., Atherton, J. J., Backs, J., Bauersachs, J., Burkhoff, D., Bonow, R. O., Chopra, V. K., de Boer, R. A., de Windt, L., Hamdani, N., Hasenfuss, G., Heymans, S., Hulot, J-S., Konstam, M., Lee, R. T., ... De Keulenaer, G. (2019). The continuous heart failure spectrum: moving beyond an ejection fraction classification. European Heart Journal, 40(26), 2155-2163. https://doi.org/10.1093/eurheartj/ehz158
    • Calore, M., Lorenzon, A., Vitiello, L., Poloni, G., Beffagna, G., Dazzo, E., Polishchuk, R., Sabatelli, P., Doliana, R., Carnevale, D., Lembo, G., Bonaldo, P., de Windt, L. J., Braghetta, P., & Rampazzo, A. (2019). A novel murine model for arrhythmogenic cardiomyopathy points to a pathogenic role of Wnt/b-catenin signaling and miRNA dysregulation. European Journal of Human Genetics, 27, 842-842.
    • Calore, M., Lorenzon, A., Vitiello, L., Poloni, G., Khan, M. A. F., Beffagna, G., Dazzo, E., Sacchetto, C., Polishchuk, R., Sabatelli, P., Doliana, R., Carnevale, D., Lembo, G., Bonaldo, P., De Windt, L., Braghetta, P., & Rampazzo, A. (2019). A novel murine model for arrhythmogenic cardiomyopathy points to a pathogenic role of Wnt signalling and miRNA dysregulation. Cardiovascular Research, 115(4), 739-751. https://doi.org/10.1093/cvr/cvy253
    • Raso, A., Dirkx, E., Philippen, L. E., Fernandez-Celis, A., De Majo, F., Sampaio-Pinto, V., Sansonetti, M., Juni, R., el Azzouzi, H., Calore, M., Bitsch, N., Olieslagers, S., Oerlemans, M. I. F. J., Huibers, M. M., de Weger, R. A., Reckman, Y. J., Pinto, Y. M., Zentilin, L., Zacchigna, S., ... De Windt, L. J. (2019). Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure. Molecular Therapy, 27(3), 584-599. https://doi.org/10.1016/j.ymthe.2018.11.011
    • Duygu, B., Juni, R., Ottaviani, L., Bitsch, N., Wit, J. B. M., de Windt, L. J., & Martins, P. A. D. C. (2019). Comparison of different chemically modified inhibitors of miR-199b in vivo. Biochemical Pharmacology, 159, 106-115. https://doi.org/10.1016/j.bcp.2018.11.013
  • 2018
    • el Azzouzi, H., & De Windt, L. J. (2018). If you like it, put a ring on it!Cardiovascular Research, 114(12), 1575-1577. https://doi.org/10.1093/cvr/cvy190
    • Mohseni, Z., Spaanderman, M. E. A., Oben, J., Calore, M., Derksen, E., Al-Nasiry, S., De Windt, L. J., & Ghossein-Doha, C. (2018). Cardiac remodeling and pre-eclampsia: an overview of microRNA expression patterns. Ultrasound in Obstetrics & Gynecology, 52(3), 310-317. https://doi.org/10.1002/uog.17516
    • De Majo, F., & De Windt, L. J. (2018). RNA therapeutics for heart disease. Biochemical Pharmacology, 155, 468-478. https://doi.org/10.1016/j.bcp.2018.07.037
    • Damanafshan, A., Elzenaar, I., Samson-Couterie, B., van der Made, I., Bourajjaj, M., van den Hoogenhof, M. M., van Veen, H. A., Picavet, D. I., Beqqali, A., Ehler, E., DeWindt, L. J., Pinto, Y. M., & van Oort, R. J. (2018). The MEF2 transcriptional target DMPK induces loss of sarcomere structure and cardiomyopathy. Cardiovascular Research, 114(11), 1474-1486. https://doi.org/10.1093/cvr/cvy091
    • Frantz, S., Falcao-Pires, I., Balligand, J-L., Bauersachs, J., Brutsaert, D., Ciccarelli, M., Dawson, D., de Windt, L. J., Giacca, M., Hamdani, N., Hilfiker-Kleiner, D., Hirsch, E., Leite-Moreira, A., Mayr, M., Thum, T., Tocchetti, C. G., van der Velden, J., Varricchi, G., & Heymans, S. (2018). The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC. European journal of heart failure, 20(3), 445-459. https://doi.org/10.1002/ejhf.1138
    • Lourenco, A. P., Leite-Moreira, A. F., Balligand, J-L., Bauersachs, J., Dawson, D., de Boer, R. A., de Windt, L. J., Falcao-Pires, I., Fontes-Carvalho, R., Franz, S., Giacca, M., Hilfiker-Kleiner, D., Hirsch, E., Maack, C., Mayr, M., Pieske, B., Thum, T., Tocchetti, C. G., Brutsaert, D. L., & Heymans, S. (2018). An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology. European journal of heart failure, 20(2), 216-227. https://doi.org/10.1002/ejhf.1059
    • Verjans, R., Peters, T., Beaumont, F., van Leeuwen, R., van Herwaarden, T., Verhesen, W., Munts, C., Bijnen, M., Henkens, M., Diez, J., de Windt, L. J., van Nieuwenhoven, F. A., van Bilsen, M., Goumans, M. J., Heymans, S., Gonzalez, A., & Schroen, B. (2018). MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart Failure. Hypertension, 71(2), 280-288. https://doi.org/10.1161/HYPERTENSIONAHA.117.10094
  • 2017
    • Dahlmans, D., Houzelle, A., Andreux, P., Jorgensen, J. A., Wang, X., de Windt, L. J., Schrauwen, P., Auwerx, J., & Hoeks, J. (2017). An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondrial metabolism. Molecular Metabolism, 6(11), 1429-1442. https://doi.org/10.1016/j.molmet.2017.08.007
    • Lorenzon, A., Calore, M., Poloni, G., De Windt, L. J., Braghetta, P., & Rampazzo, A. (2017). Wnt/beta-catenin pathway in arrhythmogenic cardiomyopathy. Oncotarget, 8(36), 60640-60655. https://doi.org/10.18632/oncotarget.17457
    • van der Harst, P., de Windt, L. J., & Chambers, J. C. (2017). Translational Perspective on Epigenetics in Cardiovascular Disease. Journal of the American College of Cardiology, 70(5), 590-606. https://doi.org/10.1016/j.jacc.2017.05.067
    • Zucker, I. H., Lindsey, M. L., Delmar, M., De Windt, L. J., Rosiers, C. D., Diz, D. I., Hester, R. L., Jones, S. P., Kanagy, N. L., Kitakaze, M., Liao, R., Lopaschuk, G. D., Patel, K. P., Recchia, F. A., Sadoshima, J., Shah, A. M., Ungvari, Z., Benjamin, I. J., Blaustein, M. P., ... Wolin, M. S. (2017). Why publish in the American Journal of Physiology-Heart and Circulatory Physiology?American Journal of Physiology-heart and Circulatory Physiology, 313(2), H221-H223. https://doi.org/10.1152/ajpheart.00329.2017
    • Perrino, C., Barabasi, A-L., Condorelli, G., Davidson, S. M., De Windt, L., Dimmeler, S., Engel, F. B., Hausenloy, D. J., Hill, J. A., Van Laake, L. W., Lecour, S., Leor, J., Madonna, R., Mayr, M., Prunier, F., Sluijter, J. P. G., Schulz, R., Thum, T., Ytrehus, K., & Ferdinandy, P. (2017). Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heartd. Cardiovascular Research, 113(7), 725-736. https://doi.org/10.1093/cvr/cvx070
    • Ghossein-Doha, C., Van Neer, J., Wissink, B., Breetveld, N. M., De Windt, L. J., Van Dijk, A. P. J., Van Der Vlugt, M. J., Janssen, M. C. H., Heidema, W. M., Scholten, R. R., & Spaanderman, M. E. A. (2017). Pre-eclampsia: an important risk factor for asymptomatic heart failure. Ultrasound in Obstetrics & Gynecology, 49(1), 143-149. https://doi.org/10.1002/uog.17343
  • 2016
    • Gupta, S. K., Foinquinos, A., Thum, S., Remke, J., Zimmer, K., Bauters, C., de Groote, P., Boon, R. A., de Windt, L. J., Preissl, S., Hein, L., Batkai, S., Pinet, F., & Thum, T. (2016). Preclinical Development of a MicroRNA-Based Therapy for Elderly Patients With Myocardial Infarction. Journal of the American College of Cardiology, 68(14), 1557-1571. https://doi.org/10.1016/j.jacc.2016.07.739
    • Ottaviani, L., De Windt, L. J., & da Costa Martins, P. A. (2016). Exosomes: scytales in the damaged heart. Annals of translational medicine, 4(11), [222]. https://doi.org/10.21037/atm.2016.05.17
    • 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), [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), [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, [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), [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), [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-+. 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), [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