Our group seeks to:
- Characterise functional heterogeneity of cardiac macrophages in homeostasis and regeneration
- Decode in vivo macrophage microenvironments and interrogate intercellular communications within the regenerating heart
- Build intracellular gene regulatory networks underpinning macrophage responses to cardiac injury
- Modelling cell-cell interactions and target discovery in heart disease by use of in vitro and ex vivo human-derived systems
The damage caused by a heart attack leads to a permanent loss of cardiac tissue in adult mammals. In contrast, zebrafish have the remarkable ability to regenerate their hearts after injury, even in the presence of scarring. Macrophages are integral to both repair by scar formation and tissue regeneration; however, the local environmental cues and cell-cell interactions that control distinct macrophage functions across the injured heart are largely unknown. How zebrafish precisely adjust the balance between a pro-fibrotic versus a pro-regenerative state is unknown. What is clear is that the zebrafish post-cardiac injury environment is unique compared to mammals and, therefore, key in elucidating how the interplay between the cardiac niche and macrophages can dictate a successful regenerative response.
Our lab is interested in dissecting the dynamic cellular crosstalk and spatial relationships occurring between macrophages and the regenerating cardiac niche. We combine a wide-range of state-of-the-art technologies like single-cell (epi)genomics, spatial-transcriptomics and proteomics, computational biology, imaging and genome-editing approaches to dissect the spatiotemporal dynamics of cellular microenvironments, identify extracellular and intercellular signalling networks and decipher how these converge to define macrophage identity, plasticity and function.
A comprehensive understanding of the regenerative microenvironment in which the innate immune response persists but is permissible for regeneration, alongside targeting of macrophage-induced pro-fibrotic pathways, is poised to assist the development of immunomodulation therapies that will enhance cardiac repair and regeneration.
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Filipa presented our work at the Biochemistry Global Summit RiboMed Satellite Conference on RNA in Disease. To all those who were in beautiful Lisbon on the 12th of July, thank you for coming! See the full programme here.