Brian's work focuses on using experimental and clinical measures along with theoretical computational models to understand physiological function across a range of scales from cells to systems. One current project uses standard clinical data from right heart catherization (RHC) and trans-thoracic echocardiography (TTE) to understand the underlying mechanistic differences between different types of heart failure. Parameters in these patient-specific models have been able to discriminate between different subclasses of heart failure with preserved ejection fraction (HFpEF). There has been considerable conversation in the field that HFpEF is a broad diagnosis that can be obtained with a multitude of sets of cardiovascular dysfunction including not only the heart but the cardiovascular system as a whole. Breaking this diagnosis into subclasses has ramifications on establishing differential treatments that can be determined on a patient to patient basis.
In another project we are using experimental data from native tissue myocardial slices and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) along with theoretical models of cardiomyocyte electrophysiology to be able to understand how to translate measured drug response in hiPSC-CMs to adult cardiomyocytes. Early work shown below explores how blockage of Na+, K+ and Ca2+ ion channels can elongate the action potential duration and generate an arrhythmogenic response. Predictions shown that regions of proarrhythmic response (black and purple regions) is more pronounced in hiPSC-CMs than in human adult ventricular cardiomyocytes (hAVCMs).
