PROJECT SUMMARY Postoperative atrial fibrillation (poAF) is a common complication of cardiothoracic surgery with an incidence between 10 and 50%. This condition typically peaks on day 2-3 following surgery. Very little remains known about the molecular mechanisms underlying poA, which makes the development of better therapies difficult. Our preliminary results suggest that patients and mice with reduced levels of ‘Striated Muscle Preferentially Expressed Protein Kinase’ (SPEG) in the atria have an increased risk of developing poAF. The overall goal of this project is to elucidate the molecular and cellular mechanisms by which reduced SPEG levels cause altered intracellular Ca2+ handling and poAF. Juwan will test the hypothesis that reduced SPEG kinase activity alters RyR2 phosphorylation and promotes poAF. In addition, he will develop improved atrial-specific gene therapy vectors for the delivery of SPEG kinase domains to atrial tissue. These preclinical studies may lead to the development of a target-based therapy for postoperative atrial fibrillation.