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:
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.
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.
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.
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.