University Research Lecturer
- British Heart Foundation Intermediate Basic Science Research Fellow
Pursuing a long-standing interest in atrial fibrillation (AF), a very common cardiac rhythm disorder, my current work is focused on the upstream molecular mechanisms causing and/or underlying adverse atrial electrical and structural (pro-fibrotic) remodelling associated with AF. An involvement of long and small non-coding RNAs, and of G-protein coupled receptors is of a particular interest in on-going projects.
This work is building up on a recent discovery of a key role of microRNA-31-5p and its downstream targets (neuronal nitric oxide synthase and dystrophin) in AF-induced electrical remodelling in atrial cardiomyoyctes. An observation that microRNA-31-5p is also up-regulated in human atrial fibroblasts in the presence of AF led to a study that is aimed to uncover fibroblasts-specific targets of microRNA-31 and investigate the impact of microRNA-31-5p on fibrogenesis in AF.
To date, therapeutic strategies to manipulate microRNAs expression and function with antagomirs or microRNA mimics are hampered by the lack of organ-specific delivery and by a short-lasting effect. Thus, understanding the mechanisms causing changes in microRNA level/expression in cardiac fibroblasts and myocytes is another focus of my work, that is intended to explore cell-specific mechanisms leading to up-regulation of microRNA-31 and of other microRNAs of interest that have been flagged up in AF. Ultimately, this work will facilitate the discovery of upstream therapeutic targets to inhibit microRNA-31 in a cell-specific manner in patients with AF. Given that current treatment of AF is associated with a higher risk of life-threatening ventricular arrhythmias and has no beneficial impact on patient’s outcome51, the discovery of novel atria-specific miR-31:mRNA interactions may inform the development of safer therapeutic strategies
A multiplex strategy combining complex molecular biology approach, transgenic murine models, high-throughput target identification strategy, genome-editing technologies and an extensive work with experimentally challenging human material are utilised in these projects. This program of research is supported by the British Heart Foundation.