Investigations into cell-specific immunometabolite-dependent signaling mechanisms underpinning cardiac–immune crosstalk

Our body continuously produces reactive chemical signals/reactive metabolites (REMs). Specialized proteins can detect and transmit REM-signals to trigger appropriate biological responses for physiological management. REMs can amplify in certain conditions, e.g., stress or injury. The location and timing of REMs determine how these signals are relayed by REM-detecting proteins into critical biological responses. Thus mapping REM proteins and clarifying their roles is essential for fundamental understanding of pathophysiological mechanisms. Growing evidence indicates that REM-signaling processes play key roles in improving wound healing following heart attack (which caused the death of 1.71 million people in the EU, making it the leading cause of death). Interestingly, some species, e.g., zebrafish, can regenerate their hearts after injury, whereas others, including humans, cannot. Evidence indicates that macrophages, components of the immune system, play crucial healing roles, regulated by REM-signals/pathways that support crosstalk between macrophages and injured heart. Unfortunately, context-specific REM-responders and signaling changes remain elusive. My host-laboratory has developed technologies that can identify and functionally investigate REM-responder proteins/pathways cell-specifically. With the support of the MSCA Fellowship, I will evolve and apply these technologies, for the first time, in state-of-the-art heart healing-relevant mechanistic models, to map cell-specific REM-responder proteins and study their mechanisms during macrophage-injured heart-cell crosstalk. My research promises breakthrough deliverables, including new models and discoveries across bioengineering, chemistry, biology, and life sciences. It could lead to innovative drug candidates and therapies boosting heart functions. The Fellowship support will allow me to advance my future independent career in academia.