Curriculum Vitae 
Lectures

Research Interest

Dr. Weiss' current research in systems biology ranges from the molecular to the integrated systems level, with a particular emphasis on integrating experimental and mathematical biology. They include:

1. Arrhythmia biology (with Peng-Sheng Chen, MD, Alan Garfinkel, PhD, Zhilin Qu, PhD, Yohannes Shiferaw, PhD, Boris Kogan, PhD, Riccardo Olcese, PhD, Lai-Hua Xie, PhD, Aman Mahajan, MD). The mechanism of sudden cardiac death due to ventricular 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, Tom Yang, PhD, Zhilin Qu, PhD). Viewing cardiac metabolism as a network of interlinked pathways (glycolysis, glycogenolysis and mitochondria) 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 ischemic preconditioning, using biochemical and imaging techniques in isolated mitochondria and isolated cardiac myocytes, as well as proteomic approaches in collaboration with the Ping and Vondriska laboratories. 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 mitochondrial depolarization waves triggering MPT in cardiac myocyte and thereby accelerating cell death. Mathematical modeling is geared to identify emergent properties at the system-wide level which act as switches determining cell fate. We are also studying the mechanisms of cellular K and Na imbalance in heart during myocardial ischemia and hypoxia. This work is currently supported by an NIH/NHLBI Program Project.

3. Inward rectifier K channels (with Scott John, PhD, Bernard Ribalet, PhD, and Lai-Hua Xie, PhD). Using mutagenesis, patch clamp and fluorescent imaging techniques, we are studying the structure-function and regulation of two classes of inward rectifier K channels: ATP-sensitive K channels (Kir6 + SUR), metabolic sensors coupling metabolism to excitability in many tissue types, and classic inward rectifier K channels Kir2 (IRK1), which regulate basal excitability in excitable tissues. This work is currently supported by an NIH/NHLBI R37 Merit Award.

Representative Publications

P. Korge, H.M. Honda and J.N. Weiss. Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning. Proc Natl Acad Sci. USA 99:3312-3317, 2002.

J.N. Weiss, P. Korge, H. Honda, P. Ping. Role of the mitochondrial permeability transition in myocardial disease. Circ. Res. 93:292-301, 2003.

L-H. Xie, S.A. John, B. Ribalet, J.N. Weiss. Long polyamines act as co-factors in PIP2 activation of inward rectifier potassium (Kir2.1) channels. J. Gen. Physiol. 126:541-549, 2005.

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.

J.N. Weiss, L. Yang, Z. Qu. Network perspective of cardiovascular metabolism. J. Lipid Res. In press, 2006.