Paul Robinson

Background and Research Interests

I am a biochemist and cell biologist with over 20 years' research experience in a clinical research environment.  I am based at the British Heart Foundation Centre for Research Excellence Laboratories at the John Radcliffe Hospital, Oxford.  I have a first degree in Medical Biochemistry from Royal Holloway College, London, and a DPhil in Clinical Medicine from 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 and calcium handling using a series of biophysical and biochemical assays with recombinant proteins.  I have also transfected cultured heart cells with recombinant HCM and DCM mutant proteins to measure contractility and calcium with the use of established and novel biosensors.  The results of this work have helped to establish a paradigm of altered muscle contractility and calcium dysregulation that is likely to cause cardiac disease.

I am also engaged in parallel work to identify novel treatments that can redress the balance between myfilament contractility, calcium handling and signalling or correct the underlying gene mutation.  I hope that the promising in vitro testing of these agents will soon translate into lifesaving and safe pharmacotherapies for HCM and DCM.

Publications

CalTrack: High Throughput Automated Calcium Transient Analysis in Cardiomyocytes.  Psaras Y et al. (2021), Circ Res. 129, 326-341

Dilated cardiomyopathy mutations in thin0filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling.  Robinson P et al. (2020), Am J Physiol Heart Circ Physiol, 319, H306-H319

Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.  Sparrow AJ et al. (2020), Am J Physiol Heart Circ Physiol, 318, H715-H722

Measurement of myofilament-localized calcium dynamics in adult cardiomyocytes and the effect of hypertrophic cardiomyopathy mutations.  Sparrow AJ et al. (2019), Circ Res, 124, 1228-1239

Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling, and stimulat Ca2+ dependent signaling.  Robinson P et al. (2018), J Biol Chem, 293, 10487-10499

Fluorescent, bioluminescent and optogenetic approachs to study excitable physiology in the single cardiomyocyte. Broyles CN et al. (2018), Cells, 7

Alpha-tropomyosin mutations in inherited cardiomyopathies.  Redwood C & Robinson P (2013), J Muscle Res Cell Motil, 34, 285-294

The effect of the dilated cardiomyopathy-causing Glu40Lys TMP1 mutation on actin-myosin interactions during the ATPase cycle.  Borovikov YS et al. (2011), Biochemical and Biophysical Research Communications, 411, 496-500

Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. Lakdawala NK et al. (2010), J Am Coll Cardiol, 55, 320-329

The effect of the dilated cardiomyopathy-cuasing mutation Glu40Lys of alpha-tropomyosin on acin-myosin interactions during the ATPase cycle.  Borovikov YS et al (2009), ARch Biochem Ciophys, 489, 20-24

Identification and functional characterization of cardiac ropnin I as a novel disease gene in autosomal dominant dilated cardiomyopathy.  Carballo S et al. (2009), Circ Res, 105, 375-382

Dilated cardiomyopathy mutations in alpha-tropomyosin inhibit its movement during the ATPase cycle.  Borovikov YS et al. (2009), Biochem Biophys Res Commun, 381, 403-406

Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effect on the calcium affinity of cardiac thin filaments.  Robinson P et al. (2007), Circ Res, 101, 1266-1273

The effect of mutations in alpha-tropomyosin (E40K and E54K) that cause familial dilated cardiomyopathy on the regulatory mechanism of cardiac muscle thin filaments.  Mirza M et al. (2007), J Biol Chem, 282, 13487-13497

Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres. Preston LC et al. (2007), Pflugers Arch, 453, 771-776

Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype. Mirza M et al (2005), J Biol Chem, 280, 28498-28506

Alterations in thin filament regulation induced by a human cardiac troponin T mutant that causes dilated cardiomyopathy are distinct from those induced by troponin T mutants that cause hypertrophic cardiomyopathy. Robison P et al. (2022), J Biol Chem, 277, 40710-40716