• Circulation Research Editorial 'Sarcomere-Directed Calcium Reporters in Cardiomyocytes'
• Meet the Author 'Alexander Sparrow'

My research focuses on the molecular mechanisms of inherited cardiomyopathies. I study inherited genetic variants in genes that encode for proteins involved in the pathogenesis of hypertrophic (HCM) and dilated (DCM) cardiomyopathy. My work has developed myofilament specific genetically encoded calcium sensors for the study of subcellular calcium dynamics in cardiomyocytes expressing HCM and DCM mutations.

My current research is in developing therapeutics by targeting the primary disease causing mechanisms of cardiomyopathies. One of the key disease mechanisms of HCM caused by mutations in thin filament regulatory proteins is increased calcium sensitivity. I am developing novel synthesised analogues of epigallocatechin-3-gallate, which decrease calcium sensitivity in cardiomyocytes. The aim of which is to provide a safe and effective treatment for patients with HCM.

My work utilises human induced pluripotent stem cell (hiPSC) derived cardiomyocytes as a cellular model when investigating inherited cardiomyopathies. Current induced pluripotent stem cell derived cardiomyocytes more closely resemble embryonic rather than adult cardiomyocytes. I have developed maturation protocols which produce an improved human cellular model to study inherited cardiomyopathies.

We are now using patient derived hiPSCs from patients with inherited cardiomyopathies to study disease mechanisms and find therapeutic targets.