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Dr Ewan Fowler
Research Fellow
School of Biosciences
- Available for postgraduate supervision
Overview
I am fascinated by the dynamic interplay between electrical activation, causing an increase then decrease in intracellular calcium, and the rise and fall of tension (excitation-contraction coupling) in the heart every time it beats. This pattern must be repeated in a coordinated manner across billions of electrically connected cells (cardiomyocytes) almost simultaneously for the heart to perform its job of pumping blood around the body effectively. When this coordinated pattern of electrical activity and calcium cycling goes wrong (at the molecular, cellular and whole heart level), the result can be catastrophic by initiating uncontrolled electrical activity (fibrillation) leading to sudden death. In particular, my work is investigating the link between abnormal calcium handling and spontaneous electrical activity in different pathological conditions such as heart failure and inherited disease. In the Cellular Cardiology Research Group we employ a broad range of techniques to address these questions, ranging from molecular biology, confocal calcium imaging and electrophysiology of cardiomyocytes, whole organ preparations, in vivo studies and in silico computer modelling.
Publication
2023
- Fowler, E. D., Azarov, J. E. and Brette, F. 2023. Editorial: Stretch and the heart: mechanoelectrical coupling and arrhythmias. Frontiers in Physiology 14, article number: 1278561. (10.3389/fphys.2023.1278561)
2022
- Fowler, E. D. and Zissimopoulos, S. 2022. Molecular, subcellular, and arrhythmogenic mechanisms in genetic RyR2 disease. Biomolecules 12(8), article number: e1030. (10.3390/biom12081030)
- Wang, N., Dries, E., Fowler, E. D., Harmer, S. C., Hancox, J. C. and Cannell, M. B. 2022. Inducing Ito,f and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene. Journal of Molecular and Cellular Cardiology 164, pp. 29-41. (10.1016/j.yjmcc.2021.11.004)
2020
- Fowler, E. D., Wang, N., Hezzell, M., Chanoit, G., Hancox, J. C. and Cannell, M. B. 2020. Arrhythmogenic late Ca2+ sparks in failing heart cells and their control by action potential configuration. Proceedings of the National Academy of Sciences 117(5), pp. 2687-2692. (10.1073/pnas.1918649117)
2019
- Fowler, E. D., Hauton, D., Boyle, J., Egginton, S., Steele, D. S. and White, E. 2019. Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system. International Journal of Molecular Sciences 20(8), article number: 1805. (10.3390/ijms20081805)
2018
- Fowler, E. D. et al. 2018. Beta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca2+ handling dysfunction in rats with pulmonary artery hypertension. Journal of Molecular and Cellular Cardiology 120, pp. 74-83. (10.1016/j.yjmcc.2018.05.015)
- Fowler, E. D., Drinkhill, M. J., Stones, R. and White, E. 2018. Diastolic dysfunction in pulmonary artery hypertension: creatine kinase and the potential therapeutic benefit of beta-blockers. Clinical and Experimental Pharmacology and Physiology 45(4), pp. 384-389. (10.1111/1440-1681.12898)
2017
- Diggle, C. P. et al. 2017. A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development. PLoS ONE 12(4), pp. e0174264. (10.1371/journal.pone.0174264)
2015
- Fowler, E. D. et al. 2015. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension. Journal of Molecular and Cellular Cardiology 86, pp. 1-8. (10.1016/j.yjmcc.2015.06.016)
- Natali, A. J., Fowler, E. D., Calaghan, S. C. and White, E. 2015. Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension. American Journal of Physiology - Heart and Circulatory Physiology 309(3), pp. H421-H424. (10.1152/ajpheart.00262.2015)
2014
- Benoist, D. et al. 2014. Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline. Progress in Biophysics and Molecular Biology 115(2-3), pp. 162-172. (10.1016/j.pbiomolbio.2014.06.008)
Articles
- Fowler, E. D., Azarov, J. E. and Brette, F. 2023. Editorial: Stretch and the heart: mechanoelectrical coupling and arrhythmias. Frontiers in Physiology 14, article number: 1278561. (10.3389/fphys.2023.1278561)
- Fowler, E. D. and Zissimopoulos, S. 2022. Molecular, subcellular, and arrhythmogenic mechanisms in genetic RyR2 disease. Biomolecules 12(8), article number: e1030. (10.3390/biom12081030)
- Wang, N., Dries, E., Fowler, E. D., Harmer, S. C., Hancox, J. C. and Cannell, M. B. 2022. Inducing Ito,f and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene. Journal of Molecular and Cellular Cardiology 164, pp. 29-41. (10.1016/j.yjmcc.2021.11.004)
- Fowler, E. D., Wang, N., Hezzell, M., Chanoit, G., Hancox, J. C. and Cannell, M. B. 2020. Arrhythmogenic late Ca2+ sparks in failing heart cells and their control by action potential configuration. Proceedings of the National Academy of Sciences 117(5), pp. 2687-2692. (10.1073/pnas.1918649117)
- Fowler, E. D., Hauton, D., Boyle, J., Egginton, S., Steele, D. S. and White, E. 2019. Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system. International Journal of Molecular Sciences 20(8), article number: 1805. (10.3390/ijms20081805)
- Fowler, E. D. et al. 2018. Beta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca2+ handling dysfunction in rats with pulmonary artery hypertension. Journal of Molecular and Cellular Cardiology 120, pp. 74-83. (10.1016/j.yjmcc.2018.05.015)
- Fowler, E. D., Drinkhill, M. J., Stones, R. and White, E. 2018. Diastolic dysfunction in pulmonary artery hypertension: creatine kinase and the potential therapeutic benefit of beta-blockers. Clinical and Experimental Pharmacology and Physiology 45(4), pp. 384-389. (10.1111/1440-1681.12898)
- Diggle, C. P. et al. 2017. A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development. PLoS ONE 12(4), pp. e0174264. (10.1371/journal.pone.0174264)
- Fowler, E. D. et al. 2015. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension. Journal of Molecular and Cellular Cardiology 86, pp. 1-8. (10.1016/j.yjmcc.2015.06.016)
- Natali, A. J., Fowler, E. D., Calaghan, S. C. and White, E. 2015. Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension. American Journal of Physiology - Heart and Circulatory Physiology 309(3), pp. H421-H424. (10.1152/ajpheart.00262.2015)
- Benoist, D. et al. 2014. Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline. Progress in Biophysics and Molecular Biology 115(2-3), pp. 162-172. (10.1016/j.pbiomolbio.2014.06.008)
Research
Heart contraction is controlled by calcium channels (called ryanodine receptors, RYR2) that open and close, allowing calcium levels in heart muscle cells to rise and fall, and the heart to contract and relax. Pathological heart conditions, such as heart failure and an inherited syndrome called CPVT, cause RYR2 to become unstable ("leaky"). Exercise and emotional stress increase Ca2+ leak and can provoke potentially fatal irregular heart rhythm. My work aims to develop new ways to make RYR2 less leaky using recombinant proteins as "model drugs" and establish whether existing drugs could be repurposed for alternate uses.
https://www.cardiff.ac.uk/biosciences/research/projects/heart-disease
Biography
I studied Human Physiology & Sport Science as an undergraduate at the University of Glasgow, followed by an MRes and PhD both in the laboratory of Prof Ed White at the University of Leeds. My work at that time focused on the role of energy systems in the failing right ventricle resulting from pulmonary arterial hypertension. I spent part of my PhD at the VU, Amsterdam, learning to perform intact myocyte stretch and contractility measurements, including physiological workloops (to simulate the in vivo cardiac pressure/volume cycle) in failing heart cells. I was a postdoctoral Research Associate in the lab of Prof Mark Cannell, University of Bristol, where I received much of my training in cardiac Ca2+ signalling and electrophysiology. I am currently funded by a 5-year British Heart Foundation Research Fellowship investigating the link between pathological "late Ca2+ sparks" and arrhythmias.
Committees and reviewing
Reviewing Editor, Frontiers in Physiology
Journal reviewer for a variety of scientific publications
Supervisions
I am always interested in supervising PhDs in the areas of:
- Cardiac pathophysiology
- Calcium imaging
- Electrophysiology
Current supervision
Gemma Toerien-Howie
Research student