Websites
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Cover of JMCC July 2023
We are hugely proud to have been awarded the front cover of the July 23 issue of The Journal of Molecular and Cellular Cardiology. Everyone loves a good pun!
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Visit the CureHeart Website
Click to see information on some of our Lab's new research initiatives and collaborators, as we attempt to correct genetic mutations in the heart.
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Podcast with AJP Heart Circ
What can three mutations in thin filament regulatory proteins associated with dilated cardiomyopathy tell us about the highly variable phenotypes of DCM? Listen as Associate Editor Crystal Ripplinger (University of California Davis) interviews lead author Paul Robinson (University of Oxford) and expert Michael Greenberg (Washington University in St. Louis) about the latest work by Robinson and co-authors
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Special Issue of JBC: The Eukaryotic Cytoskeleton
Our manuscript: Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling, and stimulate Ca2+-dependent signaling. Has been selected to appear in a special issue of the Journal of Biological Chemistry. Themed: The Eukaryotic Cytoskeleton
Paul Robinson
BSc (Hons); DPhil
Senior Postdoctoral Researcher
Researching the functional consequences of mutations in Inherited Cardiomyopathies one pathway at a time.
I am a biological scientist with 20 years research experience in a clinical research environment. I am based at the British Heart Foundation Centre for Research Excellence Laboratories in the West Wing of the John Radcliffe Hospital. I have a First degree in Medical Biochemistry from Royal Holloway College London and a DPhil in Clinical Medicine from Exeter College, Oxford. I am currently a Postdoctoral Fellow in the Radcliffe Department of Medicine (Cardiovascular Division).
The aim of my work is to investigate how subtle changes to protein structure-function caused by genetic trait variations can give rise to profound effects on cellular function and whole organ physiology. My research focuses on the function of mutant proteins that cause inherited human cardiac diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathy.
I have characterised how several disease-causing mutations in different muscle filament proteins alter muscle contraction using a series of biophysical and biochemical assays with recombinant wild type and mutant proteins. The results of this work have helped to establish a paradigm of altered muscle contractility that is likely to cause cardiac disease.
My work has diversified into the electrophysiological characterisation of isolated cardiomyocyte cultures, which have been genetically modified using adenoviral gene delivery. This work has enabled the study of downstream signalling mechanisms in the diseased cell. Moreover, it has provided a model system to use when identifying novel therapeutic agents.
More recently, I have worked on the generation and characterisation of novel genetically encoded tools to study the subcellular localisation of calcium in the adult cardiomyocyte. Calcium drives cardiomyocyte contraction via its release from the sarcoplasmic reticulum and subsequent interaction with the contractile apparatus of the sarcomere. We have discovered a causative link between altered contractility and calcium handling in HCM and DCM via changes to myofilament calcium buffering. These new tools are now enabling the group to assess the delicate interplay between calcium handling and calcium dependent signalling in different parts of the cell. Ultimately, there is a shift in this balance causing the progression of the two diseases.
I am also engaged in parallel work to identify novel drugs that have the ability to redress the balance between myofilament contractility, calcium handling and signalling. I hope that the promising in vitro testing of these agents will soon translate into lifesaving and safe pharmacotherapies for HCM and DCM in the near future.
Key publications
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Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes.
Journal article
Robinson P. et al, (2023), J Mol Cell Cardiol, 180, 44 - 57
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Dilated Cardiomyopathy Mutations in Thin Filament Regulatory Proteins Reduce Contractility, Suppress Systolic Ca2+ & Activate NFAT & AKT Signalling
Journal article
Robinson P. et al, (2020), American Journal of Physiology-Heart and Circulatory Physiology
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Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.
Journal article
Sparrow AJ. et al, (2020), American journal of physiology. Heart and circulatory physiology
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Measurement of Myofilament-Localised Calcium Dynamics in Adult Cardiomyocytes and the Effect of Hypertrophic Cardiomyopathy Mutations
Journal article
Sparrow AJ. et al, (2019), Circulation Research
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Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling and stimulate Ca2+ dependent signalling
Journal article
(2018), Journal of Biological Chemistry
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Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments.
Journal article
Robinson P. et al, (2007), Circ Res, 101, 1266 - 1273
Recent publications
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Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes.
Journal article
Robinson P. et al, (2023), J Mol Cell Cardiol, 180, 44 - 57
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CalTrack: High Throughput Automated Calcium Transient Analysis in Cardiomyocytes.
Journal article
Psaras Y. et al, (2021), Circ Res
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Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia.
Journal article
Moreira LM. et al, (2020), Nature
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Calcitonin paracrine signaling controls atrial fibrogenesis and arrhythmia
Journal article
MOREIRA LM. et al, (2020), Nature
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Dilated Cardiomyopathy Mutations in Thin Filament Regulatory Proteins Reduce Contractility, Suppress Systolic Ca2+ & Activate NFAT & AKT Signalling
Journal article
Robinson P. et al, (2020), American Journal of Physiology-Heart and Circulatory Physiology