Following a heart attack the heart tries to heal, but in humans this process often leads to scarring and weakening instead of full repair. Interestingly, some animals like zebrafish and newborn mice can completely regenerate their hearts.
This project compares detailed genetic data from humans and these animals with the power of artificial intelligence models to discover what makes repair possible. We aim to identify key genes and signals that drive human heart regeneration after injury.
Target discoveryIn depth
The injured heart undergoes coordinated phases of inflammation, proliferation and maturation, comprising interconnected biological processes that determine reparative capacity. These include regeneration of lost myocardium, recruitment and activation of immune cells, deposition and remodelling of fibrotic matrix, and restoration of coronary vasculature.
In human myocardial infarction survivors, these processes commonly lead to adverse structural remodelling and progressive functional decline. Although no current therapy enables true cardiac regeneration in humans, complete and scar-free repair occurs in specific biological contexts, notably the neonatal mouse and adult zebrafish.
Over the last years, large-scale single-nucleus and single-cell RNA sequencing datasets describing injury responses in human, adult mouse, neonatal mouse, and zebrafish hearts have been published. However, these datasets have not been systematically compared to identify conserved molecular signatures uniquely associated with regenerative competence, nor to delineate their regulatory architecture.
We aim to utilise these datasets so we can identify injury-responsive genes across species, identify cell-to-cell signalling events that act upstream of putative drivers of cardiac repair, and map transcriptional regulatory networks that regulate cardiac gene expression. This could provide therapeutic targets capable of enhancing regenerative capacity in the infarcted human heart.