Brian Carlson, Ph.D.

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. 

Workflow schematic for patient-specific classification of heart failure type using RHC and TTE clinical data. These patient-specific models once identified can also be used to predict function not currently measured clinically.

 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).

Schematic showing components included in hiPSC-CM electrophysiology model and predictied regions of arrhythmia shown by block (0 - 1 representing 100% to 0% block) of fast Na+ (axis into page), L-type Ca2+ (vertical axis) and rapid delayed rectifier K+ (horizontal axis). Regions of black and purple are predicted regions of periodic arrhythmia and sustained arrhythmia, respectively.