Heart failure progression is a complex biological process that is precipitated by the maladaptive myocardial response to injury, compounded by failure of the adult heart to replace lost or damaged cardiomyocytes. Conceivably, identifying common pathways that regulate these two seemingly unrelated processes would profoundly impact therapeutic strategies to prevent, and even reverse heart failure progression. Numerous observations by members of the proposed consortium and others support the notion that the endogenous capacity of the neonatal mammalian heart to proliferate fades in the early postnatal life as a switch from hyperplastic to hypertrophic growth of cardiomyocytes takes place. Members of the proposed consortium and others have also previously demonstrated that mechanisms linked to activation of the immune response may play a role in cardiomyocyte hypertrophy, death, healing and even stimulation of new cardiomyocyte generation. The current proposal brings together several groups with significant expertise in myocardial remodeling, regeneration and immunology with the overall goal of determining the role of immune response signaling in regulation of cardiac growth, healing and regeneration. Indeed, the immune response has taken center stage in the past several years as a primary determinant of both healthy cardiac aging and healing after injury, as well as a determinant of chronic disease states when it is inappropriately regulated. Thus, this Program will investigate a frontier and emerging area of scientific investigation involving the intersection between the immune system and the myocardium. The Administrative Core (Core A) of the proposed Program Project will provide critical administrative and logistical services of the 4 Projects as well as the two other cores, Core B and Core C. Through the highly interrelated series of experiments proposed in our four Projects, and supported by the activities of an Administrative Core (Core A), Immunology and Physiology Cores (Cores B, and C), we aim to answer questions that are crucial for understanding the role of immunity in the regulation of cardiac homeostasis and pathology. Together, these studies will test a paradigm changing hypothesis that the immune system is a critical regulator of cardiac growth and repair. The Administrative Core will be housed at University of Texas Southwestern Medical Center, Division of Cardiology. Core A will be led by Dr. Hesham Sadek and will be tasked with providing PIs and key personnel with the administrative and logistic support needed to achieve the goals of the project. Core A will provide research administrative support, fiscal and intellectual property support, facilitate communications, and provide statistical consultation for the entire Program Project. As such Core A will play a vital role as the operational manager of the Program Project.