Over the past decade, Dr. Feldman’s laboratory has been investigating the molecular and cellular pathways that are responsible for the development of heart failure. These studies have used transgenic mouse models and have focused on the role of the pro-inflammatory cytokines and signaling mediated by G protein-coupled receptors including the family of adenosine receptors and the cardiac vasopressin receptor. These studies have found that over-expression of the pro-inflammatory cytokine TNFα recapitulates the heart failure phenotype in mice. Similarly, both controlled and constitutive over-expression of G protein-coupled receptors that signal through αGs, αGi or αGq also result in the development of cardiac dysfunction. Using viral vectors to deliver genes that modify the signaling pathways down-stream of the receptors and genetically altered mice we have begun to understand the complex signaling cascade that mediates the function of these different receptors. Studies in the basic laboratory have informed translational studies in which we have found that genetic variants that modify the function of the encoded receptor can alter an individual’s response to cardiac stress or to pharmacologic therapy. In particular, these pharmacogenomic studies have focused on the β-adrenergic receptor and the A1-adenosine receptor.