Chloe Tubman

Chloe Tubman is a Postdoctoral Research Associate in the Sauka-Spengler Lab working in collaboration with Professor Paul Riley at the University of Oxford in the Department of Physiology, Anatomy and Genetics and the Institute of Developmental and Regenerative Medicine. She is investigating the molecular and cellular basis of cardiomyocyte development and regeneration in zebrafish.

Heart attacks are caused by a coronary artery occlusion which leads to ischemia, necrotic cardiac muscle cell (cardiomyocyte) death and scar formation. As mammals cannot resolve this noncontractile scar, the surviving tissue undergoes further pathological remodeling which can lead to heart failure. Unlike mammals, zebrafish are capable of regenerating their hearts following cardiac injury throughout adulthood. This is mainly driven by the dedifferentiation and proliferation of existing cardiomyocytes. However, the mechanisms underlying cardiomyocyte dedifferentiation remain unknown, while additional non-cardiomyocyte contributions to newly formed myocardium post-injury have not been unequivocally excluded. In this project, we are investigating the molecular and cellular basis of zebrafish cardiomyocyte regeneration, focusing on the role of transcription factor Wilms’ Tumour 1b (Wt1b). We have generated a number of transgenic zebrafish lines which facilitate the examination of the relative contributions of wt1b+ cells to the developing and regenerating myocardium. Moreover, they will help to identify the molecular pathways in which wt1b acts to regulate cardiomyocyte production across multiple time points. Understanding the mechanisms by which the zebrafish heart can regenerate may elucidate potential therapeutic targets for human heart attack patients. Cardiac cell types are highly conserved between fish and mammals and Wt1b has functional orthologues across species, suggesting insights gained from my project and planned future work are poised to identify areas of therapeutic potential for non-regenerating mammals and importantly, humans.