The focus of my research is application of stem cells and tissue engineering methodologies in experimental in vitro studies and cell and tissue replacement therapies. Micropatterning of extracellular matrix proteins or protein hydrogels and engineering of synthetic scaffolds are used to build stem cell-derived cardiac and skeletal muscle tissues that replicate the structure-function relationships present in healthy and diseased muscle. These systems are used to separate and systematically study the roles of structural and genetic factors that contribute cardiac and skeletal muscle function and disease at multiple organizational levels (from single cell to 3-dimensional tissue). Optical recordings with voltage and calcium sensitive dyes in synthetic tissues allow us to analyze and optimize normal electrical function as well as study complicated spatio-temporal changes in electrical activity encountered in cardiac arrhythmias and fibrillation. Contractile force measurements allow us to explore factors that would optimize mechanical function of engineered tissues. Examples of the current research projects include: 1) design of co-cultures made of cardiac and different types of stem cells to model and study cell and tissue therapies for cardiac infarction and arrhythmias, 2) local and global gene manipulation in cultures of cardiac and other cell types, 3) engineering of vascularized cardiac and skeletal muscle tissue constructs with controllable structure and function, 4) implantation of stem cell-derived cardiac tissue patches in animal models of cardiac infarction, and 5) design of synthetic excitable tissues for experimental studies and novel cell therapies.