Group Abriel

Research Focus:

The main focus of the Abriel laboratory is to investigate mechanisms underlying human diseases caused by dysfunction of ion channels, so-called channelopathies. In particular, one of the main objectives is to elucidate novel molecular and cellular mechanisms of cardiac arrhythmias causing sudden death. To this end, on the one hand, our group investigates ion channel mutations found in patients and families presenting with genetic forms of lethal arrhythmias such as the congenital long QT syndrome, Brugada syndrome, and cardiac conduction disturbances. On the other hand, we are studying new types of regulation of cardiac ion channels relevant to arrhythmogenic mechanisms. The group is currently investigating the regulation of the cardiac sodium channel Nav1.5 and its regulation by interacting proteins (funded by the Swiss National Science Foundation). Another focus is the TRP channel TRPM4 that has shown to be mutated in patients with cardiac conduction disorders. We are focusing on investigating the consequences of these mutations, as well as developing new small molecule modulators of TRPM4 in the framework of the NCCR TransCure (also funded by the Swiss National Science Foundation).

Schematic presentation
Fig. 1 Schematic presentation of the cardiac action potential and the three main ion channels that we are currently studying in the laboratory. The channel Nav1.5 mediates the rapid depolarization of the membrane, whereas the hERG and KCNQ1 channels are involved in the repolarization of the cardiac cell.

Keywords: sodium channel, potassium channel, hERG channel, TRPM4 channel, cardiac electrophysiology, congenital long QT syndrome, Brugada syndrome, cardiac conduction defects

Original Articles

Vermij S, Rougier J-S, Agullo-Pascual E, Rothenberg E, Delmar M and Abriel H. Single-molecule localization of Nav1.5 reveals different modes of reorganization at cardiomyocyte domains. BioRxiv. 2019.

Rougier J-S, Essers MC, Gillet L, Guichard S, Sonntag S, Shmerling D and Abriel H. A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes. Frontiers in physiology. 2019;10:834.

Bianchi B, Ozhathil LC, Medeiros-Domingo A, Gollob MH and Abriel H. Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to Altered Protein Stability. Frontiers in Physiology. 2018;9:177.

Ozhathil LC, Delalande C, Bianchi B, Nemeth G, Kappel S, Thomet U, Ross-Kaschitza D, Simonin C, Rubin M, Gertsch J, Lochner M, Peinelt C, Reymond J-L and Abriel H. Identification of potent and selective small molecule inhibitors of the cation channel TRPM4. British journal of pharmacology. 2018;175:2504-2519.

Bianchi B, Smith PA and Abriel H. The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration. Molecular brain. 2018;11:41.

Chevalier M, Vermij SH, Wyler K, Gillet L, Keller I and Abriel H. Transcriptomic analyses of murine ventricular cardiomyocytes. Scientific data. 2018;5:180170.

Review Articles

Rougier J-S and Abriel H. Cardiac voltage-gated calcium channel macromolecular complexes. Biochimica et biophysica acta. 2016;1863:1806-1812.

Sottas V and Abriel H. Negative-dominance phenomenon with genetic variants of the cardiac sodium channel Nav1.5. Biochimica et biophysica acta. 2016;1863:1791-1798.

Baruteau A-E, Probst V and Abriel H. Inherited progressive cardiac conduction disorders. Current opinion in cardiology. 2015;30:33-39.

Marionneau C and Abriel H. Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications. Journal of molecular and cellular cardiology. 2015;82:36-47.

Laedermann CJ, Decosterd I and Abriel H. Ubiquitylation of voltage-gated sodium channels. Handbook of experimental pharmacology. 2014;221:231-250.

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