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- Redwood Group: Cardiac Contractility Research Group
BSc (Hons); DPhil
Researching the functional consequences of mutations in Inherited Cardiomyopathies one pathway at a time.
I am a biological scientist with 16 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) and Wolfson College Oxford.
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.
Novel Potential Treatment of Familial Hypertrophic Cardiomyopathy with Analogues of the Green Tea Polyphenol Epigallocatechin-3-Gallate
Robinson PJ. et al, (2016), BIOPHYSICAL JOURNAL, 110, 125A - 125A
P387Knock-in mouse model of PRKAG2 cardiomyopathy (R299Q) exhibits altered Ca2+-dependent cardiac contractility and reduced protein kinase A activity.
Turtle C. et al, (2014), Cardiovasc Res, 103 Suppl 1
P123The rescue of Ca2+ cycling abnormalities conferred by HCM-causing mutations with analogues of the green tea polyphenol epigallocatechin-3-gallate.
Robinson P. et al, (2014), Cardiovasc Res, 103 Suppl 1
The nemaline myopathy-causing E117K mutation in β-tropomyosin reduces thin filament activation.
Karpicheva OE. et al, (2013), Arch Biochem Biophys, 536, 25 - 30
Alpha-tropomyosin mutations in inherited cardiomyopathies.
Redwood C. and Robinson P., (2013), J Muscle Res Cell Motil, 34, 285 - 294