Dr. McCulloch’s lab uses experimental and computational models to investigate the relationships between the cellular and extracellular structure of cardiac muscle and the electrical and mechanical function of the whole heart during ventricular remodeling, heart failure and arrhythmia. Current interests include developing multi-scale models of myocyte excitation-contraction coupling mechanisms and their regulation by PKA and CaMKII. Dr. McCulloch's group has also scaled cellular level models of these processes up to the tissue and organ scales to investigate mechanisms of arrhythmias and ventricular dysfunction associated with targeted gene defects and congestive heart failure. Genetically engineered mice are an important model system for developing and validating these computational models. Important phenotyping techniques in the mouse include optical electrical mapping, isolated muscle mechanics testing and magnetic resonance imaging. The lab is also developing new methods to generate patient-specifc models of the failing heart for clinical use.

A second major area of research in the lab has been the role of cytoskeletal and membrane proteins in cardiac myocyte mechanotransduction mechanisms and how defects in costameric and z-disk protein complexes can alter mechanotransduction and lead to dilated cardiomyopathy. The effects of stretch on myocyte membrane configuration and electrical conduction are also under investigation. Finally, we have been using Drosophila as a model system to explore hypoxia tolerance and susceptibility mechanisms in conjunction with metabolomics and metabolic network modeling.

Source:  http://cmrg.ucsd.edu/AndrewMcCulloch