Druv Bhagavan
Program: Biomedical Engineering
Current advisor: Jonathan R. Silva, PhD
Undergraduate university: Yale University
Research summary
The heart is a complex, multiscale, dynamic organ that converts a finely-modulated quasiperiodic electrical source signal to a mechanically-induced pulsatile fluid dynamic output. A particular domain of interest is cardiac electrophysiology and the notion of ”arrhythmogenicity.” Currently, it is difficult to link cellular-level pathology with organ-level manifestations of disease. Widely used metrics used to analyze cellular electrophysiology are temporal in nature (APD, etc.) and do not adequately characterize spatial heterogeneity, which contributes to many cardiovascular pathologies and drug effects. An illustrative example is the antiarrhythmic drug amiodarone. We have a poor, outmoded understanding of the mechanism of amiodarone’s arrhythmia resolution (which likely has a spatial component) and why it is not torsadogenic, compared to other Class III antiarrhythmic drugs. Similarly, we have a poor understanding of the electrophysiologic behavior of amiodarone metabolites and combinations thereof. These metabolites are differentially present in oral vs. IV amiodarone formulations, which have notably different electrophysiological and side-effect profiles. ;;Working in the labs of Jon Silva and Nate Huebsch, I currently aim to utilize concepts and techniques from other fields to characterize cardiac communication, with particular interest to spatiotemporal heterogeneity and its involvement in arrhythmia generation. Utilizing iPSC cardiomyocytes and in silico computational models, I hope to understand the mechanisms of arrhythmia generation and resolution. I am also interested in examining multiscale emergent phenomena and subclinical-clinical transitions of pathologic derangements of perturbed physiological dynamical systems, especially within the context of cardiovascular biomechanics and electrophysiology.
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Graduate publications
Oguntuyo K, Schuftan D, Guo J, Simmons D, Bhagavan D, Moreno JD, Kang PW, Miller E, Silva JR, Huebsch N. 2022 Robust, Automated Analysis of Electrophysiology in Induced Pluripotent Stem Cell-Derived Micro-Heart Muscle for Drug Toxicity. Tissue Eng Part C Methods, 28(9):457-468.
Mangold KE, Wang W, Johnson EK, Bhagavan D, Moreno JD, Nerbonne JM, Silva JR. 2021 Identification of structures for ion channel kinetic models. PLoS Comput Biol, 17(8):E1008932.
Bhagavan D, Padovano WM, Kovács SJ. 2020 Alternative diastolic function models of ventricular longitudinal filling velocity are mathematically identical. Am J Physiol Heart Circ Physiol, 318(5):H1059-H1067.