Postdoctoral Research Assistant in Cardiac Dynamics
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting around 2% of the population in Europe and the USA, rising to 5% in populations over the age of 65. AF is a major cause of heart failure and significantly increases the risk of stroke. The underlying mechanisms that can lead to AF are still largely unknown. As a result, current pharmacological interventions used for the treatment of AF are often non-specific and can lead to an increased risk of off-target effects, including in the ventricles where they can increase the risk of potentially fatal ventricular arrhythmias.
My research, which is supported by a grant from the British Heart Foundation, is focussed on identifying atrial specific pathways that may provide a suitable target for the development of treatments for AF without resulting in ventricular side effects. In particular, my research investigates the downstream events that occur as a result of inositol trisphosphate (IP3) signalling in atrial myocytes. IP3 is a calcium mobilising second messenger that acts via IP3 receptors (IP3R) on the sarcoplasmic reticulum. IP3R expression is significantly increased in patients with AF, and activation of the pathway can lead to an increase in potentially arrhythmogenic diastolic calcium release. Interestingly, expression of IP3R type 2 is at least six times greater in atrial compared to ventricular myocytes, raising the possibility that the IP3 pathway may be a suitable target for the development of atrial selective treatments.
My work involves the use of a range of techniques to investigate IP3 signalling, from the level of the whole tissue down to intracellular events and molecular interactions. This includes the use of electrophysiological patch-clamp recordings, live-cell calcium imaging, high resolution microscopy, immunocytochemistry and molecular biology.
IP3-mediated Ca2+ release regulates atrial Ca2+ transients and pacemaker function by stimulation of adenylyl cyclases.
Capel RA. et al, (2021), Am J Physiol Heart Circ Physiol, 320, H95 - H107
Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics.
Burton R-AB. et al, (2020), iScience, 23
Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis
Sigalas C. et al, (2020), ROYAL SOCIETY OPEN SCIENCE, 7
Towards next generation therapies for cystic fibrosis: Folding, function and pharmacology of CFTR
Bose SJ. et al, (2020), Journal of Cystic Fibrosis
A defective flexible loop contributes to the processing and gating defects of the predominant cystic fibrosis-causing mutation.
Chen X. et al, (2019), FASEB J, 33, 5126 - 5142