Translationale Kardiologie

Research group Translational Cardiology

A major focus of the Translational Cardiology group is molecular mechanisms, which control the physiology of cardiac muscle function as well as pathophysiological changes in disease. In particular, we investigate calcium transport proteins and characterize highly specialized intracellular signaling microdomains. An important example is the ryanodine receptor complex, the main intracellular calcium release channel of the heart. Ryanodine receptor dysfunction contributes to diseases like arrhythmias, heart failure, malignant hyperthermia, muscle fatigue and dystrophy, and epilepsy. Ryanodine receptors represent the main source of intracellular calcium signals, which directly controls contraction and relaxation of striated muscles. In addition, ryanodine receptors form large macromolecular sensor complexes which integrate different cell signals to modulate such essential functions as the ‘fight-or-flight’ stress response. In disease, ryanodine receptor dysfunction results in intracellular calcium "leak" and abnormal signals which may lead to cardiac arrhythmias and loss of contractile function. In addition, chronic intracellular calcium leak may contribute to maladaptive organ remodeling. Within this context we investigate molecular mechanisms which protect from abnormal ryanodine receptor function and calcium leak, how patient mutations cause disease from the molecule to the in vivo situation, and if specific molecular disease mechanisms can be targeted by novel therapeutic strategies.
We employ a variety of established and recent innovative techniques including ion channel molecular biology, lipid bilayer channel function, cell biology, confocal and 2-photon microscopy, STED nanoscopy, patch-clamp, cardiac in vivo electrophysiology, and voltage imaging of intact tissue. Different transgenic models of disease and signaling mechanisms are characterized through comprehensive studies at the organ, cell, microdomain and molecular levels. Much of our research is "translational" and meant to contribute to better understanding of the molecular basis of disease mechanisms in the heart and other organs. Additionally, novel diagnostic and therapeutic strategies are developed, some of which are currently investigated in phase II clinical trials.
To achieve these goals, we collaborate with outstanding scientists and groups as well as oversee prominent research programs. The group leader Prof. Lehnart coordinates the Clinical Research Unit KFO 155 supported by the Deutsche Forschungsgemeinschaft (DFG); a person exchange program between Goettingen and Baltimore (University of Maryland Baltimore, Lederer lab) supported by the German Academic Exchange Service (DAAD); and the large-scale FP7 consortium EUTrigTreat. We work closely with the Dept. of Biochemistry (Prof. Schwappach), the Max-Planck Institute for Dynamics and Self-Organization (Prof. Bodenschatz) and its Biomedical Physics Group (Prof. Luther), and with theMax-Planck-Institut für biophysikalische Chemie, Dept. of NanoBiophotonics (Prof. Hell). In addition, we and other investigators from the Heart Research Center Goettingen contribute to the National Genome Research Network (NGFN+) with the topic genetics of heart failure.

Team Prof. Lehnart