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

Descripción del proyecto

Mecanismos de reparación tras un infarto de miocardio

El infarto de miocardio es una de las principales causas de muerte en Europa. A diferencia del pez cebra, capaz de regenerar por completo el corazón tras una lesión, la capacidad de reparación cardíaca en el ser humano es muy limitada. Los metabolitos reactivos son reguladores fundamentales de la cardioprotección y la regeneración tisular. Sin embargo, aún no se conocen con detalle los mecanismos específicos mediante los que actúan en cada contexto. En el proyecto HEAL-REX, respaldado por las acciones Marie Skłodowska-Curie, se investigará cómo se coordina la señalización mediada por metabolitos reactivos durante interacciones específicas entre células en distintos contextos multicelulares implicados en la reparación cardíaca. Los investigadores utilizarán tecnologías avanzadas y modelos de reparación cardíaca para determinar cómo estas señales naturales de estrés modulan la respuesta cardiovascular a las lesiones. Los resultados podrían contribuir al desarrollo de futuras terapias de precisión para favorecer la reparación y regeneración de los tejidos tras un infarto de miocardio.

Objetivo

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.