Supervisor

Suitable for

Abstract

The goal of Precision Medicine is to provide therapies tailored to each patient. This is especially an urgent need in inherited heart disease, where current drug therapy mostly relies on symptom relief. In this regard, computational modelling and simulation constitutes a flexible platform for investigating the mechanisms underlying arrhythmic risk in these patients, and for the virtual screening of pharmacological therapy of both established and novel agents. 

To investigate mechanisms of arrhythmic risk and/or response to therapy using multiscale computational models (cell to whole-organ) of inherited heart disease.

Students will investigate, by means of computational modelling and simulation, how changes in structure and cellular function modulate the risk of life-threatening events and/or response to pharmacological therapy in patients with hypertrophic cardiomyopathy (HCM). Different research options will be available, including:
(i) arrhythmia mechanisms in HCM due to calcium dysregulation and spontaneous calcium release;
(ii) modelling of impaired energetics and impaired metabolism in HCM;
(iii) role of abnormalities in tissue microstructure as precursors of arrhythmic triggers;
(iv) HCM mutation-specific safety and efficacy of the latest pharmacological therapies (myosin inhibitors) when accounting for disease progression;
(v) HCM mutation-specific safety and efficacy of genetic therapy;
(vi) modelling and simulation of paediatric patients.

[1] Mechanisms of pro-arrhythmic abnormalities in
ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy. https://doi.org/10.1016/j.yjmcc.2015.09.003

[2] Improving the clinical understanding of hypertrophic
cardiomyopathy by combining patient data, machine learning and computer simulations: A case study. https://doi.org/10.1016/j.morpho.2019.09.001

[3] Electrophysiological and contractile effects of
disopyramide in patients with obstructive hypertrophic cardiomyopathy: a translational study. https://doi.org/10.1016/j.jacbts.2019.06.004

[4] Mechanism based therapies enable personalised
treatment of hypertrophic cardiomyopathy. https://doi.org/10.1038/s41598-022-26889-2

Pre-requisites: Computational Medicine (recommended)