- van Duijvenboden Karel, de Boer Bouke A., Capon Nicolas, Ruijter Jan M., Christoffels Vincent M. EMERGE: a flexible modelling framework to predict genomic regulatory elements from genomic signatures Nucleic acids research 2016;44 (5):e42 [PubMed]
- Stefanovic Sonia, Barnett Phil, van Duijvenboden Karel, Weber David, Gessler Manfred, Christoffels Vincent M. GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development Nature communications 2014;5:3680 [PubMed]
- van Weerd Jan Hendrik, Badi Ileana, van den Boogaard Malou, Stefanovic Sonia, van de Werken Harmen J. G., Gomez-Velazquez Melisa, Badia-Careaga Claudio, Manzanares Miguel, de Laat Wouter, Barnett Phil, Christoffels Vincent M. A large permissive regulatory domain exclusively controls Tbx3 expression in the cardiac conduction system Circulation research 2014;115 (4):432-441 [PubMed]
- Aanhaanen Wim T. J., Boukens Bastiaan J. D., Sizarov Aleksander, Wakker Vincent, de Gier-de Vries Corrie, van Ginneken Antoni C., Moorman Antoon F. M., Coronel Ruben, Christoffels Vincent M. Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice Journal of clinical investigation 2011;121 (2):534-544 [PubMed]
- van den Boogaard Malou, Wong L. Y. Elaine, Tessadori Federico, Bakker Martijn L., Dreizehnter Lisa K., Wakker Vincent, Bezzina Connie R., 't Hoen Peter A. C., Bakkers Jeroen, Barnett Phil, Christoffels Vincent M. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer Journal of clinical investigation 2012;122 (7):2519-2530 [PubMed]
Prof. PhD V.M. Christoffels (Transcriptional mechanism controlling heart development, regeneration and rhythm)
From 2001 I was taken on as a group leader to unravel the molecular basis of localized gene regulation and cell specification in the developing heart. In 2010 I was appointed professor of developmental biology in the department of Anatomy, Embryology & Physiology. My first breakthrough was the discovery that the location of development of the chambers and the atrioventricular canal in the heart tube is regulated by locally active T-box transcriptional repressors (Genes Dev. 2002). In 2005 I received an NWO VIDI grant to further study the role of T-box factors in the heart. A second breakthrough was the discovery that conduction system development is controlled by Tbx2 and Tbx3 (Genes Dev. 2007, Circ Res. 2008, PNAS 2012). Using genetic lineage analysis tools we addressed the contributions of different progenitor cells to the developing heart, and the role of T-box and other transcription factors in the formation of the pacemaker and conduction system components (Circ Res 2007-2010, Nature 2009). Our work on the development of the heart and conduction system has become internationally well recognized (Physiol Rev 2003, Circ Res. 2010). Recently, we uncovered a mechanism linking developmental defects of the heart and ventricular pre-excitation (JCI 2011), and, using 4C-seq and transgenesis, identified a common genetic variant in the population that disrupts T-box factor binding and sodium channel gene enhancer function in vivo (JCI 2012, Nat Genet 2013, JCI 2014). Furthermore, using in vivo ChIP-seq, we uncovered a transcriptional and epigenetic mechanism for the specification of the atrioventricular canal of the heart involving GATA transcription factors and tissue-specific histone (de)acetylation (Nat Commun). Genetic variants in the human genome influence cardiac development and heart rhythm/arrhythmia risk. Current research focuses on identifying the transcriptional mechanisms underlying this phenomenon. Furthermore, we are exploring the transcriptional mechanisms that (re)program the pacemaker and conduction system cells of the heart.
Theme: Cardiovascular Diseases This research group participates in Heart Failure Research Center
Faculty
PhD P. Barnett
PhD A.V. Postma
Postdocs
PhD S. Ahuja
PhD F.M. Bosada-Musselwhite
PhD J.A. Janssen
MSc PhD B. Jensen
Others
C. de Gier-de Vries
BEng V. Wakker
- AMC (Vrijgesteld)
- Fondation Leducq
- Nederlandse Hartstichting
- UCLA Cardiac Arrhythmia Center
- ZonMw