We strive to translate basic research findings into clinical applications and to approach clinical problems through fundamental and translational research. To his purpose, we make use of the principles & tools of (synthetic) biology, mathematics, engineering and medicine. These are applied to various complementary in silico (computer-based), in vitro, ex vivo, and in vivo models for studies on increasing levels of complexity, i.e from molecule to whole organism. Of particular interest is the use of viral vectors to investigate the consequences of inhibiting or stimulating the expression of specific genes or the signaling through certain pathways and for translational research aimed at developing (synthetic) biomedical interventions, like cardiac gene therapy. We are particularly interested in gain-of-novel functions like those obtained upon optogenetic engineering of the heart, i.e. generation of endogenous photocurrents for arrhythmia termination. The diverse technical skills and theoretical knowledge required for this type of integrative research is provided by a research team consisting of people with different scientific backgrounds and expertises varying from electrophysiology, biophysics and mathematics to cardiology, cell biology and virology.
The Laboratory of Experimental Cardiology is located on the 4th floor of the LUMC and possesses state-of-the-art facilities for the transient and permanent genetic modification of cells, tissues and organs by viral gene transfer systems including adeno-associated virus and lentivirus vectors. In addition, all necessary readout-systems are present for studying the effects of specific (optogenetic) interventions, including polymerase chain reaction analyses, flow cytometry, immunocytology, Western-blotting, immunohistology and histochemistry as well as electrophysiological measurements and heart function assessments. The electrical properties of cells, tissues and the whole heart are investigated using whole-cell patch-clamp, multi-electrode array, optical mapping and electrocardiographic techniques. Heart function is measured using echocardiography, micro-magnetic resonance imaging and by the assessment of pressure-volume relationships with the aid of a conductance catheter.
Current research projects
Underlying mechanisms of cardiac arrhythmias and cardiac cell differentiation
Here we investigate the molecular pathogenesis & underlying mechanisms of cardiac arrhythmias, and the molecular mechanisms involved in the cardiac differentiation of (stem) cells, especially those related to excitability. For this we employ various techniques, but of special interest is the use of optogenetics to identify and study the role of a certain protein or biologicial process in cardiac electrophysiology and/or differentiation by precisely controlling their function in both magnitude, time and space.
Biological cardiac rhythm control
To date, cardiac arrhythmia research and management heavily rely on modulation of cardiac electrical function through drugs, ablation or electroshocks, which are all non-biological and rather unspecific, irreversible or traumatizing interventions. Here we aim to understand how drugs, software, wires and metal can be replaced by genes, proteins, and tissue (i.e. the heart itself) in favour of a more effective, broadly applicable and trauma-free treatment option for cardiac arrhythmias. For example, we are investigating how the heart could act as a defibrillator.
Biological cardiac repair
Loss of myocardial tissue remains a leading cause of disease and death, as the adult heart has insufficient regenerative potential. In contrast to current approaches of cardiac regeneration, like cell therapy, which showed disappointing clinical effects and only little evidence for robust cardiac regeneration, we aim to understand how the heart itself could detect and repair damage. For this and other purposes, we have established lines of conditionally immortalized cardiomyocytes, which allows us to take an unique approach.
We have received financial support from The European Research Council, Netherlands Organisation for Scientific Research, Dutch Heart Foundation, Ammodo,The Netherlands Organisation for Health Research and Development, and The Royal Netherlands Academy for Arts and Sciences. Please see Links page for more information.