Oxford BHF CRE Basic Science Intermediate Transition Fellow
- Start Date: 01/10/2019
- End Date: 31/12/2021
- BHF CRE Mentors: Prof Hugh Watkins & Prof Charles Redwood
Where am I now?
I have been awarded a Sir Henry Dale Fellowship, by the Royal Society and the Wellcome Trust, which will start in October 2021. This 5 year fellowship will support the further development of my research group in the Division of Cardiovascular Medicine at the University of Oxford.
Research project title: Defining Key Mechanisms of HCM and DCM Variant Pathogenicity in a Human Cellular Model of Disease
We investigate the role of mutations in key contractile proteins in hypertrophic cardiomyopathy (HCM). The laboratory focuses on CRISPR/Cas-9 engineering of human induced pluripotent stem cells. These cells can be differentiated into cardiomyocytes, which are used to model human heart disease in a dish.
Photo: Human cardiomyocyte derived from a human stem cell that has the contractile unit of the cell, the sarcomere, labelled with GFP.
I have always been fascinated about the way the heart functions, and the processes that govern how the muscle of the heart is able to efficiently pump blood around the body. I spent my doctoral years dissecting key mechanisms of heart muscle regulation. I then moved to Boston to study how these mechanisms can go wrong in disease. I have since returned to Oxford to begin my own research group to identify these key mechanisms of disease and understand how we can design novel therapies for patients with these cardiac conditions.
2019-2021 British Heart Foundation Centre of Research Excellence Intermediate Fellow. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford. Fellowship title: Defining key mechanisms of HCM and DCM variant pathogenicity in a human cellular model of disease.
2018-2019 Eugene Braunwald Named Fellowship of Brigham and Women’s Hospital, Harvard Medical School, Boston. Department of Genetics and Brigham and Women’s Hospital, Harvard Medical School, Boston. https://cvls.bwh.harvard.edu/division-honors/
2017-2021 Sir Henry Wellcome Fellowship, Wellcome Trust. Department of Genetics, Harvard Medical School & Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
2015-2017 Post-doctoral Fellow Harvard Medical School. Department of Genetics, Harvard Medical School, Boston.
2010-2015 Wellcome Trust/NIH 4 year PhD studentship. PhD funded by the Wellcome Trust and National Institutes of Health investigating the role of myosin light chain phosphorylation on the stress response of the heart. In Professor Michael Ferenczi’s laboratory (NHLI, Imperial College London) and Dr James Seller’s laboratory (NHLBI, NIH). Thesis title ‘The role of myosin regulatory light chain phosphorylation in cardiac health and disease’
2007-2010 BSc Biomedical Science Imperial College London.
Mechanism based therapies enable personalised treatment of hypertrophic cardiomyopathy
Margara F. et al, (2022), Scientific Reports, 12
Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere.
Agarwal R. et al, (2022), Circulation
Filamin C Cardiomyopathy Variants Cause Protein and Lysosome Accumulation
Agarwal R. et al, (2021), Circulation Research