Every heartbeat requires a large change in the level of calcium ions within cardiac cells (cardiomyocytes). This involves release of internal calcium stores caused by the opening of a channel structure known as the cardiac ryanodine receptor (RyR2), which is a large protein composed of four equal subunits. Abnormal RyR2 opening-closing is caused by genetic defects or environmental factors that can produce an irregular heartbeat (arrhythmias) and sudden death.

Research in my laboratory is focused on understanding the structure-function relationship of the RyR2 calcium release channel, as well as its regulation by accessory proteins including calsequestrin and the FK506-binding proteins. Our specific aims are twofold:  first, to elucidate the molecular mechanism(s) underlying RyR2 channel dysfunction and abnormal cardiomyocyte calcium handling in arrhythmogenic disorders. Second, to identify drug(s) that restore RyR2 protein-protein interactions and normal channel properties in order to improve intracellular calcium handling and cardiac function. We use various computational, molecular, cellular and physiological approaches, which are available in my group or provided through collaborators with established expertise. My group is supported by the British Heart Foundation (past Intermediate Fellowship and current Senior Research Fellowship).

Areas of Expertise

  • Calcium signalling
  • Excitation-contraction coupling
  • Arrhythmogenic cardiac disease

Publications

  1. Zisimopoulos, S. Association of cardiac myosin-binding protein-C with the ryanodine receptor channel – putative retrograde regulation? Journal of Cell Science 131 15 jcs210443
  2. Zisimopoulos, S. Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study Journal of Visualized Experiments 113
  3. Zisimopoulos, S. Structural and functional interactions within ryanodine receptor Biochemical Society Transactions 43 3 377 383
  4. Zisimopoulos, S. Non-ventricular, Clinical, and Functional Features of the RyR2R420Q Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia Revista Española de Cardiología (English Edition) 68 5 398 407
  5. Zisimopoulos, S. Early Remodeling of Perinuclear Ca2+ Stores and Nucleoplasmic Ca2+ Signaling During the Development of Hypertrophy and Heart Failure Circulation 130 3 244 255

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Teaching

  • PM-266C Y System Gardiofasgwlaidd

    Gan adeiladu ar fodiwl y flwyddyn gyntaf, Ffisioleg Ddynol (PM-139), bydd y modiwl ar y System Gardiofasgwlaidd yn cyflwyno ac yn diffinio'r mecanweithiau cellol sylfaenol sy'n rheoli ffisioleg gweithrediad system gardiofasgwlaidd iach. Bydd y modiwl yn disgrifio'r prosesau sy'n gyfrifol am guriad calon rheolaidd a gweithrediad y pibellau gwaed, a sut gall newidiadau yn y systemau dan sylw arwain at gyflyrau pathoffisiolegol. Bydd pwyslais ar y dulliau arbrofol a ddefnyddir i astudio'r mecanweithiau cardiofasgwlaidd a ddisgrifiwyd.