Research groups
Abigail Wilson
DPhil Student
I am a DPhil student funded by the British Heart Foundation and based in the Sitsapesan lab. The cardiac ryanodine receptor (RyR2) is located in the sarcoplasmic reticulum (SR) and is the main intracellular Ca2+ release channel in the heart with a crucial role in regulating contraction. My research aims to identify how RyR2 is regulated by physiological stimuli such as phosphorylation, by the lipid SR membrane environment and by other SR ion channels in the SR (for example, TRIC-A).
I am also investigating why specific single point mutations to RyR2 can cause life threatening arrhythmias as in the disease catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is a rare inherited heart arrhythmia found in young people and children, which can lead to sudden cardiac death. To investigate how mutations in RyR2 affect electromechanical coupling within the heart, I am using single ion-channel reconstitution experiments to elucidate differences in the biophysical properties of the mutated channel, as well as using patient derived induced pluripotent stem cells (IPSCs) and optical mapping to examine the effect of the mutation at the whole cell level.
Recent publications
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Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.
Journal article
Elbaz M. et al, (2019), Hum Mol Genet
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Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform.
Journal article
Venturi E. et al, (2018), Br J Pharmacol, 175, 938 - 952
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Atorvastatin Activates Skeletal RyR1 Channels: Towards Reducing Statin Side-Effects
Conference paper
Lindsay C. et al, (2018), BIOPHYSICAL JOURNAL, 114, 470A - 470A
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Statins Bind to Cardiac Ryanodine Receptor (RyR2) Channels to Alter Opening Frequency
Conference paper
Wilson AD. et al, (2018), BIOPHYSICAL JOURNAL, 114, 621A - 622A
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Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A.
Journal article
El-Ajouz S. et al, (2017), J Physiol, 595, 4769 - 4784