The Shaw lab takes a cell biology approach to explore the complexity of cardiac myocytes. Heart failure progression and sudden cardiac death are secondary to altered homeostatic organization of cardiac myocytes. The lab seeks to understand the pathways that organize these cells and the mechanisms by which their organization is altered in disease. Major contributions from the Shaw lab include elucidation of the “directed targeting” model of channel delivery, which explains how cytoskeleton targets ion channels to specific membrane subdomains. In particular the lab determined how gap junctions are targeted to intercalated discs, and L-type calcium channels targeted to T-tubules, and mechanisms by which this forward trafficking is disturbed in heart failure. The lab has also recently focused on alternative translation, identifying that the mRNA of a major gap junction protein generates in human heart multiple small truncated isoforms that autoregulate the larger protein’s movements. A translational application of the lab research is the development of a blood-based cardiac assay that correlates with myocardial reserve, providing both prognosis and arrhythmogenic potential. Future efforts will be directed toward translating these new insights in basic cardiac myocyte biology to new diagnostics and therapeutics for heart failure and malignant arrhythmias.