J. I. Vandenberg

Potassium dependent structural changes in the selectivity filter of HERG potassium channels

The paper determines structures of conductive and non-conductive HERG selectivity filters and identifies a mechanism for rapid inactivation kinetics.

Slow conduction and spatial dispersion of repolarization are intrinsic properties of cardiomyocyte electrophysiology that contribute to proarrhythmia in an iPSC model of hypertrophic cardiomyopathy

This study shows that HCM cardiomyocytes have slower conduction and increased repolarization dispersion, which contribute to arrhythmia in an iPSC model.

Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology

The paper identifies the axis of arrhythmia, a metric to assess drug-induced arrhythmia risk using electrophysiological simulations of cardiomyocytes, achieving 88.1-90.8% accuracy in predicting clinical risk labels.

A Massively Parallel Trafficking Assay Accurately Predicts Loss of Channel Function in KCNH2 Variants

The paper develops a trafficking assay to predict KCNH2 variant function, showing high accuracy in classifying loss-of-function variants compared to existing methods.

Heterozygous KCNH2 variant phenotyping using Flp-In HEK293 and high-throughput automated patch clamp electrophysiology

This paper describes a high-throughput method to phenotype KCNH2 variants using automated patch-clamp electrophysiology and Flp-In HEK293 cells, enabling rapid assessment of variant function.

Arrhythmogenesis as the failure of repolarization

This paper proposes a new mechanism for arrhythmogenesis where cardiac cells failing to repolarize act as focal ectopic sources, leading to fibrillation, and shows that arrhythmia susceptibility is higher at tissue boundaries.

Co-expression of calcium channels and delayed rectifier potassium channels protects the heart from proarrhythmic events

The paper identifies co-expression of CACNA1C and KCNH2 in cardiac cells as protective against proarrhythmic events through reduced action potential variability.

Protocol-dependent differences in IC50 values measured in hERG assays occur in a predictable way and can be used to quantify state preference of drug binding.

This study shows that IC50 differences in hERG assays depend predictably on drug binding states and can be modeled using machine learning.

Sinusoidal Voltage Protocols For Rapid Characterisation Of Ion Channel Kinetics

This paper introduces a method using sinusoidal voltage protocols to rapidly characterize ion channel kinetics, demonstrating improved predictive models of ion currents in hERG channels.