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

  • 2024
    • Vilaça, A., Jesus, C., Lino, M., Hayman, D., Emanueli, C., Terracciano, C. M., Fernandes, H., de Windt, L. J., & Ferreira, L. (2024). Extracellular vesicle transfer of lncRNA H19 splice variants to cardiac cells. Molecular Therapy - Nucleic Acids, 35(3), Article 102233. https://doi.org/10.1016/j.omtn.2024.102233
    • Beslika, E., Leite-Moreira, A., De Windt, L. J., & da Costa Martins, P. (2024). Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis. Cardiovascular Research, 120(5), 461-475. https://doi.org/10.1093/cvr/cvae045
    • Spanò, G., Pehlivanoglu, S., & De Windt, L. J. (2024). Heracles and the Lernaean Hydra: uncovering new layers of transcriptome regulation. Cardiovascular Research, 120(1), 10-12. https://doi.org/10.1093/cvr/cvad192
  • 2023
    • Rabussier, G., Bunter, I., Bouwhuis, J., Soragni, C., van Zijp, T., Ng, C. P., Domansky, K., Windt, L. J. D., Vulto, P., Murdoch, C. E., Bircsak, K. M., & Lanz, H. L. (2023). Healthy and diseased placental barrier on-a-chip models suitable for standardized studies. Acta Biomaterialia, 164(1), 363-376. https://doi.org/10.1016/j.actbio.2023.04.033
    • Juni, R. P., Kocken, J. M. M., Abreu, R. C., Ottaviani, L., Davalan, T., Duygu, B., Poels, E. M., Vasilevich, A., Hegenbarth, J. C., Appari, M., Bitsch, N., Olieslagers, S., Schrijvers, D. M., Stoll, M., Heineke, J., de Boer, J., de Windt, L. J., & da Costa, P. A. (2023). MicroRNA-216a is essential for cardiac angiogenesis. Molecular Therapy, 31(6), 1807-1828. https://doi.org/10.1016/j.ymthe.2023.04.007
    • Soragni, C., Vergroesen, T., Hettema, N., Rabussier, G., Lanz, H. L., Trietsch, S. J., de Windt, L. J., & Ng, C. P. (2023). Quantify permeability using on-a-chip models in high-throughput applications. STAR protocols, 4(1), Article 102051. https://doi.org/10.1016/j.xpro.2023.102051
    • de Boer, M., Hekkert, M. T., Chang, J., van Thiel, B. S., Martens, L., Bos, M. M., de Kleijnen, M. G. J., Ridwan, Y., Octavia, Y., van Deel, E. D., Blonden, L. A., Brandt, R. M. C., Barnhoorn, S., Bautista-Nino, P. K., Krabbendam-Peters, I., Wolswinkel, R., Arshi, B., Ghanbari, M., Kupatt, C., ... Duncker, D. J. (2023). DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice. Aging Cell, 22(3), Article e13768. https://doi.org/10.1111/acel.13768
    • Vilaça, A., de Windt, L. J., Fernandes, H., & Ferreira, L. (2023). Strategies and challenges for non-viral delivery of non-coding RNAs to the heart. Trends in Molecular Medicine, 29(1), 70-91. https://doi.org/10.1016/j.molmed.2022.10.002
  • 2022
    • Hegenbarth, J. C., De Majo, F., Spano, G., Olieslagers, S., Esfandyari, D., Tiburcy, M., Zimmermann, W. H., Stoll, M., & de Windt, L. (2022). Machine learning-assisted integration of single cell transcriptomic data identifies potential cardiomyocyte maturation genes. Journal of Molecular and Cellular Cardiology, 173, S47-S47. https://doi.org/10.1016/j.yjmcc.2022.08.094
    • Spano, G., Hegenbarth, J. C., De Majo, F., Tiburcy, M., Zimmermann, W. H., & de Windt, L. (2022). RNA m6A modification governs early human cardiomyocyte commitment. Journal of Molecular and Cellular Cardiology, 173, S108-S109. https://doi.org/10.1016/j.yjmcc.2022.08.215
    • De Windt, L. J. (2022). Grand challenges in molecular cardiology. Frontiers in Molecular Medicine, 2, Article 920039. https://doi.org/10.3389/fmmed.2022.920039
    • Soragni, C., Rabussier, G., Lanz, H. L., Bircsak, K. M., de Windt, L. J., Trietsch, S. J., Murdoch, C. E., & Ng, C. P. (2022). A versatile multiplexed assay to quantify intracellular ROS and cell viability in 3D on-a-chip models. Redox Biology, 57, Article 102488. https://doi.org/10.1016/j.redox.2022.102488
    • Videira, R. F., Koop, A. M. C., Ottaviani, L., Poels, E. M., Kocken, J. M. M., Dos Remedios, C., Mendes-Ferreira, P., Van De Kolk, K. W., Du Marchie Sarvaas, G. J., Lourenço, A., Llucià-Valldeperas, A., Nascimento, D. S., de Windt, L. J., De Man, F. S., Falcão-Pires, I., Berger, R. M. F., & da Costa Martins, P. (2022). The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload. Cardiovascular Research, 118(12), 2688-2702. https://doi.org/10.1093/cvr/cvab299
    • Raso, A., Dirkx, E., Sampaio-Pinto, V., El Azzouzi, H., Cubero, R. J., Sorensen, D. W., Ottaviani, L., Olieslagers, S., Huibers, M. M., de Weger, R., Siddiqi, S., Moimas, S., Torrini, C., Zentillin, L., Braga, L., Nascimento, D. S., da Costa Martins, P. A., van Berlo, J. H., Zacchigna, S., ... De Windt, L. J. (2022). Author Correction: A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nature Communications, 13(1), Article 4977. https://doi.org/10.1038/s41467-022-32785-0
    • Sansonetti, M., & De Windt, L. J. (2022). Non-coding RNAs in cardiac inflammation: key drivers in the pathophysiology of heart failure. Cardiovascular Research, 118(9), 2058-2073. https://doi.org/10.1093/cvr/cvab192
    • Spano, G., De Majo, F., Hegenbarth, J. C., Tiburcy, M., Zimmermann, W. H., & De Windt, L. J. (2022). m6A modification regulates early human cardiomyocyte lineage specification. Cardiovascular Research, 118(SUPPL 1). https://doi.org/10.1093/cvr/cvac066.004
    • Ottaviani, L., Juni, R. P., de Abreu, R. C., Sansonetti, M., Sampaio-Pinto, V., Halkein, J., Hegenbarth, J. C., Ring, N., Knoops, K., Kocken, J. M. M., Jesus, C. D., Ernault, A. C., El Azzouzi, H., Rühle, F., Olieslagers, S., Fernandes, H., Ferreira, L., Braga, L., Stoll, M., ... da Costa Martins, P. A. (2022). Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells. Molecular Therapy, 30(6), 2257-2273. https://doi.org/10.1016/j.ymthe.2022.03.002
    • Vilaca, A., Fernandes, H., de Windt, L., & Ferreira, L. (2022). H19-Enriched Extracellular Vesicles Promote Angiogenesis In Vitro. Tissue Engineering, 28, S354-S354.
    • de Windt, L. (2022). Small Tricks To Mend A Broken Heart. Tissue Engineering, 28, S643-S643.
    • Mangraviti, N., & De Windt, L. J. (2022). Long Non-Coding RNAs in Cardiac Hypertrophy. Frontiers in Molecular Medicine, 2, Article 836418. https://doi.org/10.3389/fmmed.2022.836418
    • Hegenbarth, J.-C., Lezzoche, G., De Windt, L. J., & Stoll, M. (2022). Perspectives on Bulk-Tissue RNA Sequencing and Single-Cell RNA Sequencing for Cardiac Transcriptomics. Frontiers in Molecular Medicine, 2, Article 839338. https://doi.org/10.3389/fmmed.2022.839338
  • 2021
    • Gandhi, S., Witten, A., De Majo, F., Gilbers, M., Maessen, J., Schotten, U., de Windt, L. J., & Stoll, M. (2021). Evolutionarily conserved transcriptional landscape of the heart defining the chamber specific physiology. Genomics, 113(6), 3782-3792. https://doi.org/10.1016/j.ygeno.2021.09.002
    • Sacchetto, C., Mohseni, Z., Colpaert, R. M. W., Vitiello, L., De Bortoli, M., Vonhogen, I. G. C., Xiao, K., Poloni, G., Lorenzon, A., Romualdi, C., Bariani, R., Mazzotti, E., Daliento, L., Bauce, B., Corrado, D., Thum, T., Rampazzo, A., de Windt, L. J., & Calore, M. (2021). Circulating miR-185-5p as a Potential Biomarker for Arrhythmogenic Right Ventricular Cardiomyopathy. Cells, 10(10), Article 2578. https://doi.org/10.3390/cells10102578
    • De Majo, F., Martens, L., Hegenbarth, J. C., Ruhle, F., Hamczyk, M. R., Nevado, R. M., Andres, V., Hilbold, E., Bar, C., Thum, T., de Boer, M., Duncker, D. J., Schroen, B., Armand, A. S., Stoll, M., & De Windt, L. J. (2021). Genomic instability in the naturally and prematurely aged myocardium. Proceedings of the National Academy of Sciences of the United States of America, 118(36), Article e2022974118. https://doi.org/10.1073/pnas.2022974118
    • Raso, A., Dirkx, E., Sampaio-Pinto, V., el Azzouzi, H., Cubero, R. J., Sorensen, D. W., Ottaviani, L., Olieslagers, S., Huibers, M. M., de Weger, R., Siddiqi, S., Moimas, S., Torrini, C., Zentillin, L., Braga, L., Nascimento, D. S., da Costa Martins, P. A., van Berlo, J. H., Zacchigna, S., ... De Windt, L. J. (2021). A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nature Communications, 12(1), Article 4808. https://doi.org/10.1038/s41467-021-25211-4
    • Badimon, L., Robinson, E. L., Jusic, A., Carpusca, I., DeWindt, L. J., Emanueli, C., Ferdinandy, P., Gu, W., Gyongyosi, M., Hackl, M., Karaduzovic-Hadziabdic, K., Lustrek, M., Martelli, F., Nham, E., Potocnjak, I., Satagopam, V., Schneider, R., Thum, T., & Devaux, Y. (2021). Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129. Cardiovascular Research, 117(8), 1823-1840. https://doi.org/10.1093/cvr/cvab094
    • Vilaca, A., Sansonetti, M., Fernandes, H., de Windt, L., & Ferreira, L. (2021). Extracellular vesicles as lncRNA-H19 carriers to the cardiovascular system. European Journal of Clinical Investigation, 51, 108-109.
  • 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, Article 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
    • Vonhogen, I. G. C., Mohseni, Z., Winkens, B., Xiao, K., Thum, T., Calore, M., Martins, P. A. D. C., de Windt, L. J., Spaanderman, M. E. A., & Ghossein-Doha, C. (2020). Circulating miR-216a as a biomarker of metabolic alterations and obesity in women. Non-Coding rna research, 5(3), 144-152. https://doi.org/10.1016/j.ncrna.2020.08.001
    • 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), Article 8136. https://doi.org/10.1038/s41598-020-65115-9
    • Sacchetto, C., Vitiello, L., de Windt, L. J., Rampazzo, A., & Calore, M. (2020). Modeling Cardiovascular Diseases with hiPSC-Derived Cardiomyocytes in 2D and 3D Cultures. International Journal of Molecular Sciences, 21(9), Article 3404. https://doi.org/10.3390/ijms21093404
    • 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), Article 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
    • De Windt, L. J., & Giacca, M. (2018). Non-coding RNA function in stem cells and Regenerative Medicine. Non-coding RNA research, 3(2), 39-41. https://doi.org/10.1016/j.ncrna.2018.04.004
    • 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