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Radcliffe Department of Medicine
I achieved a Bachelor of Arts (with Honours) degree at the University of Cambridge in Natural Sciences, specialising in the Department of Zoology. I then obtained a Master of Research degree in Molecular and Cellular Biosciences at Imperial College London. I am now a DPhil candidate at the University of Oxford, funded by the Wellcome Trust as part of the Chromosome and Developmental Biology programme. After a 3 month rotation project, in September 2019 I began my DPhil project with Professor Paul Riley at the Department of Physiology, Anatomy and Genetics, in collaboration with Associate Professor Tatjana Sauka-Spengler at the MRC Weatherall Institute of Molecular Medicine. In this project I will examine the contribution of the epicardium to adult heart regeneration after cardiac injury in zebrafish.
Heart attacks are caused by a coronary artery occlusion which leads to ischaemia, necrotic cardiac muscle cell (cardiomyocyte) death and scar formation. As mammals cannot resolve this noncontractile scar, the surviving tissue undergoes further pathological remodelling which can lead to heart failure. Unlike mammals, zebrafish retain the ability to resolve scarring and regenerate cardiac tissue into adulthood. While it’s known that zebrafish regenerate their hearts through the de-differentiation and proliferation of cardiomyocytes, the role of progenitor cells is less well understood.
The epicardium is a single-cell layer of multipotent progenitors that contribute to the generation of many cardiac cell types during development. After injury, the epicardium re-expresses embryonic genes and is essential for zebrafish heart regeneration. In accordance with evidence from preliminary lineage tracing experiments, we hypothesise that after heart injury the zebrafish epicardium becomes “re-activated” and contributes to de novo cardiomyocyte generation and/or that wt1b re-expression plays a role in existing cardiomyocyte de-differentiation, to facilitate heart muscle regeneration. I will use a range of imaging and biochemical techniques on genetically modified zebrafish to investigate these hypotheses, with the aim of furthering our understanding of zebrafish cardiac regeneration to extrapolate to mammals and identify potential novel therapeutic approaches for patients.