Our laboratory studies transcriptional processes that are disrupted in disease. We identified a novel transcriptional signaling pathway in the heart that mediates the heart’s ability to regulate whole body metabolism. Through a combination of pharmacological and genetic gain- and loss-of-function studies in mice, we found the heart is capable of regulating whole body metabolism through a mechanism that is governed by MED13 and miR-208a. MED13 is a particularly interesting component of the Mediator complex because it functions as a molecular bridge between the core complex and kinase submodule, providing a mechanism for spatial and temporal control of Mediator-dependent regulation of transcription. In addition, we are studying the function of multiple components of Mediator including CDK8, CDK19, MED12 and CycC. We primarily utilize mutant mouse models to study the proteomic, molecular, bioinformatic and biochemical methods to study the molecular signaling events controlling cardiac response to stress.