Our lab studies the physiology, pharmacology and biophysics of ion channels. Ion channel proteins form ion-selective pores within cell membranes and in the heart they establish and maintain normal cardiac rate and rhythm. A major focus of our research is on hERG channels, which are critical to normal cardiac repolarization. Inherited mutations in the hERG channel gene, or drug-induced inhibition of channel function lead to inherited or acquired Long QT syndrome (LQTS) and the development of lethal cardiac arrhthymias. As such, hERG channels are the main target for proarrhythmogenic screening during drug development. Clinical management of individuals harbouring inherited hERG mutations would also be improved by better understanding of how channel phenotype may be influenced by genetic modifiers. We use techniques and models including optical mapping of ex vivo hearts, conventional and fluorescence-coupled electrophysiology (e.g. patch clamp, TEVC, voltage clamp fluorimetry, LRET), molecular modelling, proteomics, CRISPR-Cas9 gene-editing, iPSC-derived cardiomyocytes, zebrafish hearts, heterologous expression systems (e.g. HEK, Xenopus). Our goal is to better understand channel function and regulation to discover novel therapeutic targets and mechanisms for the treatment and management of LQTS.
Current or recent research funding: