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Transcriptional regulation in the post MI border zone cardiomyocytes

Vincent Christoffel

Professor Vincent Christoffels
Academic Medical Centre Amsterdam


Bio

My research goal is to develop a comprehensive understanding of the gene regulatory mechanisms that control heart development, rhythm and stress. As an undergraduate, I conducted research on the transcriptional regulation of esterase genes in Acinetobacter. As a predoctoral student with Wouter Lamers, my research focussed on the liver zone-specific and hormone-controlled transcription of urea cycle gene Cps1 in mouse. During this period I visited the lab of Thierry Grange in Paris to gain expertise in analyses of transcription factor function (such as foot printing). During a postdoctoral training with Greg Winter in Cambridge, UK, I used phage display technology to select cell surface-specific single chain antibodies. I continued my research career in the lab of Antoon Moorman on the spatio-temporal regulation of gene expression during heart morphogenesis. We described a novel model for cardiac chamber and conduction system development, and identified underlying transcriptional regulatory mechanisms, including the role of T-box transcription factors. We found a mechanism linking developmental defects of the heart and ventricular pre-excitation, and identified a common genetic variant in the population that disrupts T-box factor binding and sodium channel gene enhancer function in vivo. We uncovered a molecular mechanism for conduction system-specific gene activity in vivo. My work on the development of the heart and conduction system has become internationally well recognized (e.g. Physiol Rev 2003, Circ Res 2010, Development 2016, Nat Rev Cardiol 2018). In 2001 I became group leader, in 2005 associate professor, in 2010 full professor, and in 2012 head of the department. I have organized a Keystone Symposium on Cardiovascular Development and Regeneration. I am the European coordinator of a prestigious Leducq Transatlantic Network of Excellence Program grant, in which US and EU researchers address the genetics and epigenomics of atrial fibrillation. Furthermore, I coordinate a Netherlands Heart Foundation consortium of pediatric cardiology research groups to study heart regeneration in the context of congenital heart defects.