My primary work is an extension of my dissertation research, which consists of a mathematical modeling project incorporating data from Dr. Erwin Shibata’s lab (University of Iowa) related to caveolae, microdomains on the cardiac cell membrane. The Shibata lab discovered that caveolae serve as reservoirs of “recruitable” sodium ion channels that open in response to certain hormonal stimuli. As such, caveolae constitute a previously unrecognized source of electric current that may may influence the action potential, the electrical event responsible for the contraction of heart cells, thereby modifying overall heart function.
The main goal of this research is to gain insight, via mathematical modeling, into the role that caveolae-associated ion currents play in determining cardiac action potential morphology and contributing to arrhythmogenesis.
Simulations using my caveolae-inclusive models suggest that stochasticity in caveolar opening can delay cell repolarization and initiate early afterdepolarizations which are both electrophysiological hallmarks of a serious form or cardiac arrhythmia known as Long-QT Syndrome (LQTS). Interestingly, mutations in the gene that encodes for caveolin-3, the primary scaffolding protein for cardiac caveolae, are known to be associated with a type of LQTS, but so far the precise link between caveolae and LQTS has remained elusive. My findings, which were published in the journal Frontiers in Physiology, suggest that mutation-induced caveolar stochasticity would be sufficient to produce this type of arrhythmia.
Thus far my work has focused primarily on modeling single-cell dynamics using systems of nonlinear, coupled ordinary differential equations. However, in his senior capstone project, one of my students used the spatially-extended version (in one spatial dimension) of a relatively simple cardiac model to began an exploration of caveolar sodium’s effects on excitatory wave propagation. Future work will continue to build upon these results.