I am Rahul, a new doctoral student at the DRIVE-RM consortium. I’ve joined the group of Jeroen Bakkers, to study the role of the high mobility group A protein (HMGA1) in cardiac regeneration pathways. We’ve known for a while that certain organisms, such as the zebrafish we study, are capable of regenerating their injured hearts without the development of scar tissue or permanent loss of function. While mammals are capable of similar regeneration in the embryonic stage, we lose it soon afterwards and instead rely on a limited healing pathway with scarring and reduced capacity.
Previous research by our group comparing zebrafish and mammalian regeneration showed that HMGA1 was one of the genes responsible for the differences in outcomes. It codes for a non-histone chromatin protein that alters the structure of DNA, making it more open to transcription and enabling new pathways. It’s involved in critical processes like cellular dedifferentiation and proliferation, both of which are essential for regenerating tissue. In fact, by artificially inducing HMGA1 expression in adult mammalian hearts, we've seen promising signs that regeneration is possible, even in hearts that normally heal with permanent scar tissue and reduced function.
Why does this matter? The WHO estimates that cardiovascular diseases are responsible for a higher mortality than any other category of disease. Our work has the potential to change that. We hope to harness the power of HMGA1 to permit scar-free and complete healing of injured human hearts.
But our vision doesn’t stop with the heart. As part of a larger consortium on regeneration, I’m aware the heart isn’t the only organ that could benefit from this knowledge. There are others who study the incredible limb regeneration capabilities of certain salamanders. Even in mammals, the liver is known to possess a remarkable capacity to regenerate throughout life. My project aims to explore whether HMGA1 plays a broader, perhaps even universal, function in regeneration across these diverse systems.
To do this, I’ll be working collaboratively with researchers to study a diversity of tissues. To this end, we’re always looking to collaborate and understand regeneration in models that we’re not familiar with ourselves.
I’m personally very fascinated about the possibility of discovering this possible universal regeneration mechanism that could be switched on and off on demand.
