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Dr Spyridon Zisimopoulos

Dr Spyridon Zisimopoulos

Associate Professor, Medicine

Telephone number

+44 (0) 1792 513440

Research Links

Academic Office - 142
First Floor
Institute of Life Science 1
Singleton Campus
Available For Postgraduate Supervision

About

Spyros is a British Heart Foundation Senior Research Fellow and Associate Professor with 20 years research experience in excitation-contraction coupling and calcium signalling. Spyros obtained a BSc in Chemistry from the University of Athens, Greece, and an MSc in Biochemistry & Molecular Biology from King’s College London. He was awarded a PhD from the University of Wales College of Medicine for the characterisation of the ryanodine receptor calcium release channel complex. Spyros was based for several years in the Wales Heart Research Institute, Cardiff, with like-minded researchers (Tony Lai, Alan Williams, Chris George, Lowri Thomas) to acquire and expand his expertise in bioinformatics, molecular biology, biochemistry, biophysical single channel characterisation, fluorescence and confocal microscopy. Spyros’ independent career was kickstarted by a BHF Intermediate Research Fellowship in 2009 and was consolidated by a BHF Senior Research Fellowship in 2015. He has been in Swansea Medical School since 2017 and was appointed as an Associate Professor in 2020.  

Spyros’ main research is on the structure-function analysis of the ryanodine receptor calcium release channel and its role in arrhythmias and sudden cardiac death. A particular ambition is the identification of novel anti-arrhythmic drugs that specifically target and stabilise ryanodine receptor function. 

Areas Of Expertise

  • Calcium signalling
  • Excitation-contraction coupling
  • Molecular mechanisms of disease
  • Protein-protein interactions
  • Calcium release channel activity

Career Highlights

Teaching Interests

Spyros has supervised several PGR students at both the MSc and PhD level. He is also actively contributing to teaching on the Applied Medical Sciences BSc programme. 

Research

Every heartbeat is mediated by a synchronised transient rise of calcium ions inside cardiac cells. Calcium is mobilised from an intracellular store via the ryanodine receptor (RyR2), a protein pore composed of four equal subunits. RyR2 channel activity (opening and closing of the pore) is tightly regulated by discrete interactions (direct physical contacts) within a subunit as well as between the four neighbouring subunits. Moreover, RyR2 activity is fine-tuned by accessory proteins. Abnormal RyR2 calcium release leads to irregular heartbeat (arrhythmia) and sudden death. Numerous RyR2 mutations (genetic defects in the building blocks of the protein) have been associated with arrhythmogenic cardiac disease. The most common treatment is pharmacological blockade of β-adrenergic receptors (beta blockers) but its efficacy is highly variable. 

Research in Spyros’ laboratory is focused on understanding the intrinsic regulation of the homotetrameric RyR2 channel via intra- and inter-subunit interactions, as well as its regulation by accessory proteins including calsequestrin and the FK506-binding proteins. It employs a range of experimental techniques including computational, molecular, cellular and in vivo approaches, available in Spyros’ group or provided through collaborators with established expertise, to achieve two specific aims. First, to elucidate the molecular mechanisms underlying RyR2 channel dysfunction and abnormal calcium handling in arrhythmogenic disorders. Second, to identify novel chemical compounds that specifically restore RyR2 interactions and normalise channel properties in order to improve intracellular calcium handling and cardiac function. Spyros’ research is largely supported by the British Heart Foundation. 

Award Highlights

British Heart Foundation Senior Research Fellowship, 2015

British Heart Foundation Intermediate Research Fellowship, 2009

Collaborations

Academic collaborations include the University of Cambridge, Cardiff University, University College London, University of Oxford, Université Paris-Sud (France) and Qatar University.