Editorials
- Circulation Research Editorial 'Sarcomere-Directed Calcium Reporters in Cardiomyocytes'
- Meet the Author 'Alexander Sparrow'
Alexander Sparrow
BSc (Hons), MSc, PhD
Senior Postdoctoral Researcher
My research combines understanding the molecular mechanisms of inherited cardiomyopathies and developing genetic therapies. As a senior postdoctoral researcher on CureHeart I am developing innovative gene editing tools to correct the genetic variants that cause inherited cardiomyopathies.
I have studied 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 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 test genetic therapies.
Key publications
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Measurement of Myofilament-Localized Calcium Dynamics in Adult Cardiomyocytes and the Effect of Hypertrophic Cardiomyopathy Mutations.
Journal article
Sparrow AJ. et al, (2019), Circ Res, 124, 1228 - 1239
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Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.
Journal article
Sparrow AJ. et al, (2020), Am J Physiol Heart Circ Physiol, 318, H715 - H722
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LIM kinase function and renal growth: Potential role for LIM kinases in fetal programming of kidney development.
Journal article
Sparrow AJ. et al, (2017), Life Sci, 186, 17 - 24
Recent publications
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Nutraceuticals silybin B, resveratrol, and epigallocatechin-3 gallate-bind to cardiac muscle troponin to restore the loss of lusitropy caused by cardiomyopathy mutations in vitro, in vivo, and in silico.
Journal article
Yang Z. et al, (2024), Front Physiol, 15
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Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes.
Journal article
Robinson P. et al, (2023), J Mol Cell Cardiol, 180, 44 - 57
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CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes.
Journal article
Psaras Y. et al, (2021), Circ Res, 129, 326 - 341
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Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia.
Journal article
Moreira LM. et al, (2020), Nature, 587, 460 - 465
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Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling.
Journal article
Robinson P. et al, (2020), Am J Physiol Heart Circ Physiol, 319, H306 - H319
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Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.
Journal article
Sparrow AJ. et al, (2020), Am J Physiol Heart Circ Physiol, 318, H715 - H722