Using Physics to Understand the Heart

Zhen Song
Ph.D., Physics
Advisor: Prof. Alain Karma
Song was the recipient of a prestigious American Heart Association pre-doctoral fellowship
First Job: Cardiovascular Research Laboratories, David Geffen School of Medicine, at UCLA (post-doc)

“The American Heart/Stroke Association is committed to identifying and supporting specific science areas deemed vital to achieving their mission and strategic objectives,” says Song. “The Association has established partnerships with various organizations to fund critical-need, high-impact, and focused research programs. I currently hold an American Heart Association (AHA) pre-doctoral fellowship, which aims at helping students initiate careers in cardiovascular and stroke research by providing research assistance and training.”

Song received the AHA pre-doctoral fellowship in July 2011. “Under the guidance of Professor Karma, I proposed a project using computer models to study arrhythmogenic effects of calsequestrin mutations,” he says. “Triggered activity often causes life-threatening reentrant cardiac arrhythmias. Various forms of triggered activity have been linked with mutations of one or several cardiac membrane ion channels in the setting of the inherited Long QT (LQT) syndrome, or with mutations of calcium cycling proteins as in the setting of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), which is an inherited life-threatening electrical disturbance of the heart. Carriers of LQT mutations are at risk for polymoriphic ventricular tachycardias such as torsade de pointes (TdP) and/or sudden cardiac arrest.”

Song says considerable progress has been made in the molecular characterization of various cardiac gene mutations in several congenital diseases, but arrhythmogenic mechanisms of triggered activity are varied and complex and remain not completely understood, even at a cellular level.

“A main reason is that triggered activity at this level results from the complex interaction of a very large number of cardiac membrane ion channels and calcium cycling proteins,” he says. “Thus, it is generally extremely difficult, if not impossible, to predict the effect of one defective gene-coded functional protein, taken in isolation, without considering its interaction with all the other normally-functioning cardiac proteins. From this standpoint, in-silico electrophysiological computer models of cardiac activity provide a powerful tool to study this complex interaction in order to gain basic mechanisms of triggered activity and arrhythmias. The overarching goal of my proposed doctoral research is to further develop and use a new physiologically detailed in-silico electrophysiology model of the ventricular myocyte to gain basic insights into calcium-mediated cellular mechanisms of triggered activity.”

Overall, Song says his research goal is to understand the basic arrhythmogenic mechanisms of CPVT. CPVT occurs in genetically-predisposed individuals without structural cardiac abnormalities.

“It is typically manifested as syncope in the setting of physical activity or acute emotion,” Song says. “Even though CPVT is a rare disorder, it is estimated to account for roughly 15 percent of all sudden cardiac deaths in young people. Even though we focus specifically on a rare genetic disorder, the insights derived from this study are also expected to be relevant for other diseases such as the LQT syndrome and heart failure. Also, while this investigation is limited to a cellular level, we expect the insights to provide a basis to understand mechanisms of triggered activity at the organ level where they become even more complex.

Lastly, ventricular fibrillation remains a major cause of sudden death in the US and worldwide. The novel insights into mechanisms of triggered activity from the study should provide an improved basis for risk stratification in a broad population and the development of reliable antifibrillatory drug therapies.”

Song began a postdoctoral fellowship this spring at Cardiovascular Research Laboratories, David Geffen School of Medicine, at UCLA.

This entry was posted in Uncategorized. Bookmark the permalink. Both comments and trackbacks are currently closed.