A groundbreaking research initiative is poised to illuminate the intricate molecular pathways of stressed heart muscle cells by scrutinizing the role of mono-ADP-ribosyltransferase-1 (ART1) in inducing post-translational modifications. ART1, an enzyme responsible for transferring an ADP-ribose moiety from NAD+ to arginine-rich target proteins, opens doors to understanding molecular signaling pathways that govern crucial processes such as gene regulation, DNA repair, inflammation and cell death. While extensive research has been conducted on poly-ADP-ribosylation (PARylation), the downstream implications of mono-ADP-ribosylation (MARylation) remain relatively enigmatic, primarily due to historical limitations in reagent availability. With a focus on ART1, an enzyme highly expressed in the heart, skeletal muscle and select cancer cells, this project aims to establish the pivotal role of ART1 and identify potential target proteins in stressed cardiac cells. Dr. Brendon Stiles' oncology laboratory at Montefiore Einstein, part of the cardiothoracic surgery department, has recently developed a humanized therapeutic monoclonal antibody (22C12) that effectively binds to ART1, inhibiting MARylation. This innovative antibody will undergo rigorous testing to evaluate its capacity to prevent heart cell injury and fibrosis while preserving cardiac function in preclinical murine ischemia/reperfusion models.