Associate Professor of Cardiovascular Science
- 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.
BK ablation attenuates osteoblast bone formation via integrin pathway.
Wang Y. et al, (2019), Cell Death Dis, 10
Insights into pancreatic β cell energy metabolism using rodent β cell models [version 3; peer review: 2 approved, 1 not approved]
Morten KJ. et al, (2019), Wellcome Open Research, 2
NEONATAL MICRO-RNA PROFILE DETERMINES ENDOTHELIAL FUNCTION IN OFFSPRING OF HYPERTENSIVE PREGNANCIES
Yu G. et al, (2018), Hypertension
Insights into pancreatic β cell energy metabolism using rodent β cell models
Morten K. et al, (2017), Wellcome Open Research
Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase.
Reilly SN. et al, (2017), Science translational medicine, 8, 340ra74 - 340ra74