Saleet Jafri, George Mason University, “Computational Studies of Cardiac Excitation-Contraction Coupling: From Molecule to Arrhythmia”

March 4, 2013 @ 12:00 pm – 1:00 pm

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“Computational Studies of Cardiac Excitation-Contraction Coupling: From Molecule to Arrhythmia”

Prof. M. Saleet Jafri is currently a Professor in the School of Systems Biology and Department of Molecular Neuroscience at George Mason University. His research uses computational models to understand the molecular and cellular basis of disease. He received his BS in mathematics from Duke University, a MS in mathematics from the Courant Institute of Mathematical Science at New York University, and a PhD in Biomathematical Sciences from the Mount Sinai School of Medicine/City University of New York. He did his postdoctoral training with Joel Keizer at the University of California Davis followed by a Research Assistant Professorship at the Johns Hopkins University in the Department of Biomedical Engineering. He served as an Assistant Professor in the Department of Mathematical Sciences at the University of Texas at Dallas before joining George Mason University in 2002.



“Computational Studies of Cardiac Excitation-Contraction Coupling: From Molecule to Arrhythmia”

Calcium dynamics in the cardiac myocyte links the electrical excitation of the heart to contraction in a process known as excitation-contraction coupling. Dysfunction of critical calcium signaling proteins in heart is associated with lethal inherited cardiac arrhythmias. However, how the altered proteins lead to arrhythmias remains both unknown and controversial. We have used computational models to investigate fundamental mechanisms that underlie calcium-dependent arrhythmias, the same class of arrhythmias that follow myocardial infarction, heart failure and diverse genetic arrhythmic diseases. Even very common arrhythmias (one episode of sudden cardiac death in a month) are rare when normalized to the events occurring within a single cell over the period of a typical long experiment (e.g. one hour). Stochastic modeling, however, with the powerful computer clusters available and with our recent advances in computational algorithms, enable us to examine stochastic model systems over prolonged periods without missing the rare events. We start with the most elementary event of cardiac calcium release, the calcium spark, and construct stochastic models that explain mechanisms of calcium release termination, calcium homeostasis and the sarcoplasmic reticulum calcium leak, and the generation of arrhythmias from defects in calcium signaling. These insights begin to provide insight in to the normal and abnormal physiology of cardiac excitation-contraction coupling.

Note: Light lunch will be served starting at 11:30am.


JHU - Institute for Computational Medicine