British Heart Foundation
DPHIL OPPORTUNITIES AVAILABLE
Associate Professor of Cardiovascular Science
- British Heart Foundation Intermediate Basic Science Research Fellow
Pursuing a long-standing interest in cardiology and adverse myocardial remodelling, our main focus is to understand the mechanisms of two major, often linked, heart conditions cardiac fibrosis and atrial fibrillation.
The main goal of our research is to uncover new important mechanisms underlying and causing these challenging conditions in order to identify therapeutic targets. To achieve our research goal we combine advanced laboratory techniques (e.g., molecular, RNA/DNA/microRNA biology), extensive cellular assays in native human cardiofibroblasts and cardiomyocytes, high throughput proteomic and transcriptomic profiling and comprehensive in vivo studies in cell-targeted genetically-modified mice. To maximise scientific and translational potential of our work, we established successful partnership with several world-leading labs.
Cardiac fibrosis is a hallmark histological feature of structural changes in the myocardium associated with virtually all cardiac diseases (e.g., heart failure, cardiomyopathies, hypertension, atrial fibrillation and myocarditis). To date, there is no effective treatment for cardiac fibrosis, as we do not understand the mechanisms contributing or causing it. Our group is very interested in uncovering new potentially important pathways accountable for this condition. For example, we explore the role of calcitonin receptor, one of G-protein coupled receptors, and it’s downstream signalling pathways in cardiac fibrogenesis. We also aim to comprehensively study disease-specific transcriptional signature of cardiac fibroblasts using single-cell RNA-sequencing approach in cells obtained from patients with heart diseases, which are underlied by cardiac fibrosis. These studies will help us to uncover new important mechanisms causing and contributing to the development of cardiac fibrosis, a very serious incurable condition.
Atrial fibrillation is the most common cardiac arrhythmia in humans. Changes in calcium handling have been long implicated in this arrhythmia, as calcium is a key ion in electrophysiological function of cardiomyocytes (a major muscle cell type of the heart). However, the upstream mechanisms underlying changes in calcium handling in atrial fibrillation are still unclear. Thus, we are interested in elucidating electrophysiological and arrhythmogenic responses of murine, guinea pig and human cardiomyocytes to a number of pro- and anti-arrhythmic molecules. In addition, we also aim to clarify the role of liver-kinase B1 (LKB1) signalling in human atrial fibrillation. These studies will help us to identify new players in the arrhythmogenesis of atrial fibrillation.
Clinical studies in patients focus on testing new biomarkers and mediators of cardiac conditions including, but not limited to, cardiac fibrosis and atrial fibrillation.
Animal studies use advanced mouse models with gene deletion or overexpression targeted to a specific heart chamber (i.e., atria or ventricle) and cell type (i.e., cardiofibroblasts and cardiomyocytes). These studies are performed in collaboration with the top international labs (in the USA and Canada).
Structural biology work aims to understand the function of calcitonin singalling via calcitonin receptor at the molecular level using sophisticated methods such as X-ray crystallography. This work is performed in collaboration with National Physical Laboratories (UK) and Diamond Light Source (UK).
All our work is facilitated by a number of internal and external collaborations including Oxford University, King’s College London, Montreal Heart Institute (Canada), Baylor College of Medicine (USA), Essen Institute of Pharmacology (Germany) and LIRYC Electrophysiology and Heart Modelling Institute (France).
Our program of research is mainly supported by the British Heart Foundation.
SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development.
Zhou S. et al, (2023), Biomed Pharmacother, 159
Emerging Role for Branched-Chain Amino Acids Metabolism in Fibrosis.
Wu T. et al, (2022), Pharmacol Res
Mouse models of spontaneous atrial fibrillation.
Keefe JA. et al, (2022), Mamm Genome
Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis.
Wang M. et al, (2022), J Nanobiotechnology, 20
ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype.
Sheldon H. et al, (2021), Int J Mol Sci, 22