Curriculum Vitae

Research Interest

Dr. Weiss's current research utilizes systems approaches integrating experimental biology at the molecular to organ levels with mathematical modeling and nonlinear dynamics to investigate the following areas:

1. Arrhythmia biology (with Peng-Sheng Chen, MD, Alan Garfinkel, PhD, Zhilin Qu, PhD, H. Karagueuzian, PhD, Boris Kogan, PhD, Riccardo Olcese, PhD, Lai-Hua Xie, PhD). The mechanism of ventricular and atrial fibrillation is being studied using interdisciplinary experimental and mathematical approaches. The experimental component uses high resolution multielectrode and optical arrhythmia mapping in intact tissue and monolayers, and patch clamp and fluorescent dye studies in isolated cells. The theoretical component integrates nonlinear dynamics (including chaos theory) with computer simulations of spiral and scroll wave reentry in 2D and 3D cardiac tissue. The goal is to use insights from nonlinear dynamics to develop novel gene-, pharmacologic- and pacing-based therapeutic strategies. This work is currently supported by an NIH/NHLBI Program Project.

2. Ischemia biology and cardioprotection (with Paavo Korge, PhD, Henry Honda, MD, Jun-Hai Yang, PhD, Zhilin Qu, PhD). Viewing cardiac metabolism as a network of interlinked pathways (glycolysis, glycogenolysis and oxidative phosphorylation) regulated by multiple protein kinase signaling pathways, our goal is to integrate experimental and mathematical approaches to understand global system-wide responses of metabolism to stresses such as ischemia/reperfusion. A major focus is on the role of the mitochondrial permeability transition (MPT) in ischemia/reperfusion injury and cardioprotection, using biochemical and imaging techniques in isolated mitochondria and cardiac myocytes, as well as proteomic approaches in collaboration with the Ping laboratory. Major goals are to understand the mechanism by which mitochondrial ATP-sensitive K channel agonists and protein kinase signaling pathways are cardioprotective, and to investigate the role of metabolic oscillations in accelerating cell death. Mathematical modeling is geared to identify properties at the system-wide level which act as switches determining cell fate. This work is currently supported by an NIH/NHLBI Program Project and an R01.

Representative Publications

J.N. Weiss, A. Karma, Y. Shiferaw, P-S. Chen, A. Garfinkel, Z. Qu. From pulsus to pulseless: the saga of cardiac alternans. Circ. Res. 98;1244-1253, 2006.

L. Xie, F. Chen, H. Karagueuzian, J.N. Weiss. Oxidative stress-induced afterdepolarizations and Calmodulin kinase II signaling. Circ. Res. 104: 79-86, 2009.

D. Sato, L-H. Xie, D.X. Tran, F. Xie, A. Garfinkel, J.N. Weiss, Z. Qu. Synchronization of chaotic early afterdepolarization in the genesis of cardiac arrhythmias. Proc Natl Acad Sci U.S.A. In press, 2009.

J.N. Weiss, L. Yang, Z. Qu. Network perspective of cardiovascular metabolism. J. Lipid Res. 47:2355-2366, 2006.

P. Korge, P. Ping, J.N. Weiss. Reactive oxygen species production and suppression by nitric oxide in energized cardiac mitochondria subjected to hypoxia/reoxygenation. Circ Res. 103:873-880, 2008.

J-H. Yang, L. Yang, Z. Qu, J.N. Weiss. Glycolytic oscillations in isolated rabbit ventricular myocytes. J Biol Chem. 283:36321-36327, 2008.