Dr. Roger Hajjar’s laboratory is focused on the role of abnormal calcium handling in the development and pathogenesis of heart failure. The laboratory’s research efforts have concentrated on investigating calcium cycling in failing hearts by targeting specific excitation-contraction related proteins in cardiac myocytes. In studies using myocytes isolated from failing human, the laboratory has used gene transfer techniques to demonstrate that enhanced activity of the sarcoplasmic reticulum Ca2+ATPase (SERCA2a) pump via overexpression, or modulation of key regulatory proteins, is the most efficacious strategy to improve contractile function in heart failure. To validate these studies in vivo, the laboratory of Dr Hajjar has established the methodology to direct viral vectors to the myocardium in both rodent and large animal models to induce homogeneous expression of various intracellular proteins. Today, these techniques serve as the gold standard for in vivo gene transfer to the myocardium and are employed by a multitude of laboratories. The laboratory has extended these studies in large animal models and is developing novel molecular imaging techniques to better track gene transfer. In addition, Dr Hajjar has used both genomics and proteomics approaches to identify new targets based on the restoration of contractile function following SERCA2a gene transfer. Enthusiasm for the large body of data generated by Dr. Hajjar’s laboratory to establish SERCA2a as a key target for gene transfer in heart failure has culminated in the initiation of a NIH-funded clinical trial of gene therapy during cardiac surgery targeting SERCA2a in patients with advanced heart failure and in multiple other trials using catheter based techniques to deliver SERCA2a by percutaneous approaches in patients with intractable heart failure. These trials will demonstrate the bench-to-bedside application of his research.