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BHF Fellow set to advance pro-regeneration heart therapies

Congratulations to Dr Filipa Simões who has been awarded a British Heart Foundation (BHF) Intermediate Basic Science Research Fellowship. She will investigate how immune cells called macrophages facilitate long-lasting heart regeneration in the zebrafish and how this could be harnessed for the human heart.

Filipa Simoes and Injured Zebrafish Heart.jpg
Image Credit: Filipa Simoes/Adam Gault

The zebrafish injured heart: many different cell types compose the heart and the way these cells communicate with each other is key in jumpstarting a regenerative response post injury 

The damage caused by a heart attack leads to a permanent loss of cardiac tissue in adult mammals. The human heart cannot replenish these lost cells, instead forming a permanent cardiac scar, which will eventually lead to heart failure. In contrast, the zebrafish, a freshwater fish native to South Asia, has the ability to fully regenerate its heart after injury, even in the presence of scarring, because its cardiac scar is only temporary as new cardiac muscle cells are formed. In early 2020, a Riley group study led by Dr Filipa Simões revealed that macrophages are integral to both repair by scar formation and tissue regeneration. However, scientists so far have been unable to uncover the mechanisms behind the behaviour of macrophages that allows zebrafish to adjust the balance between a pro-fibrotic versus a pro-regenerative state. According to Dr Simões:

“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.”

Dr Simões has now been awarded a BHF Intermediate Basic Science Research Fellowship to pursue a project entitled “Niche-Dependent Programming of Macrophage Function in the Regenerating Heart” for the next five years. In this time, she plans to dissect the dynamic cellular crosstalk and spatial relationships occurring between macrophages and the regenerating cardiac niche using a range of cutting-edge techniques such as single-cell (epi)genomics, spatial-transcriptomics and proteomics, imaging, and genome-editing approaches. Her work is set to contribute to the development of therapeutic strategies aimed at harnessing pro-regenerative intercellular communications within the injured non-regenerative mammalian heart.

The new Fellowship, which follows a pivotal Transitional Fellowship by the Oxford BHF Centre of Research Excellence, will allow Dr Simões to establish her independent research programme as Principal Investigator at the IDRM in Spring 2022. She will work closely with collaborators from neighbouring institutes: Professor Stephen Sansom (The Kennedy Institute of Rheumatology), Professor Roman Fisher (Target Discovery Institute), and Professor Tatjana Sauka-Spengler (Radcliffe Department of Medicine).

Dr Simões said: “Joining the IDRM represents a unique and exciting opportunity that will springboard my independent research. This flagship institute will provide an outstanding interdisciplinary environment with all the core facilities needed to meet my research objectives and will bring together a critical mass of world-renowned cardiovascular scientists, neurobiologists and immunologists, fostering excellent collaborative opportunities that will enhance my independent career. Particularly relevant to my proposal, the IDRM will physically merge the areas of cardiovascular sciences and immunology, creating a unique multidisciplinary environment to host my group. I am very excited about this next stage of my career and can’t wait to get started!”

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