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 myofilament 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

1. Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes. Robinson P. et al (2023) Journal of Molecular and Cellular Cardiology

2. Dilated cardiomyopathy mutations in thin filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling.  Robinson P et al. (2020), American Journal of Physiology Heart and Circulatory Physiology
3. Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.  Sparrow AJ et al. (2020), American Journal of Physiology Heart and Circulatory Physiology
4. Measurement of myofilament-localized calcium dynamics in adult cardiomyocytes and the effect of hypertrophic cardiomyopathy mutations.  Sparrow AJ et al. (2019), Circulation Research
5. Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling, and stimulat Ca2+ dependent signaling.  Robinson P et al. (2018), Journal of Biological Chemistry
6. Identification and functional characterization of cardiac troponin I as a novel disease gene in autosomal dominant dilated cardiomyopathy.  Carballo S et al. (2009), Circulation Research
7. 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), Circulation Research