Dr. James N. Weiss
Cardiac Biology
3645 MRL
310-825-9029
jweiss@mednet.ucla.edu 

Research Interests:

Our interdisciplinary research group focuses on cardiac systems biology, integrating experimental and mathematical biology to relate molecular events to systems level responses in the following areas: 

Arrhythmia biology.  Our goal is to understand the mechanisms of sudden cardiac death due to ventricular fibrillation. The experimental component uses high resolution optical arrhythmia mapping in intact tissue and monolayers, and patch clamp and fluorescent dye studies in isolated cells.  The mathematical component integrates nonlinear dynamics 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. Viewing cardiac metabolism as a network of interlinked pathways (glycolysis, glycogenolysis and mitochondria) regulated by multiple protein kinase signaling pathways, our goal is understand how these pathways interact to produce global system-wide responses to stresses such as ischemia/reperfusion.  A major focus is on the role of the mitochondrial permeability transition (MPT) in ischemia/reperfusion injury, and the mechanisms by which mitochondrial ATP-sensitive K channels and protein kinase signaling pathways are cardioprotective.  Experimental approaches use biochemical and imaging techniques in isolated mitochondria and cardiac myocytes and tissue, as well as proteomic approaches in collaboration with the Ping and Vondriska laboratories. Mathematical modeling is geared to understand how molecular events lead to emergent behaviors at the systems level, such as metabolic oscillations, and the impact on cell fate. This work is currently supported by an NIH/NHLBI Program Project and an NIH RO1.

Inward rectifier K channels. Using mutagenesis, patch clamp and fluorescent imaging techniques, we study 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:

Chen, B.M. and Grinnell, A.D. (1997) Kinetics, Ca++ dependence, and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor neerve terminals. J. Neurosci.  17:904-916

Yazejian, B.M., Sun, X.-P., and Grinnell, A.D. (2000) Tracking presynaptic Ca++ dynamics during neurotransmitter release with Ca++-activated K+ channels. Nature Neurosci. 3:566-571.

Sun, V.-P., Yazejian, B, and Grinnell, A.D. (2004) Electrophysiological properties of BK channels in Xenopus motor nerve terminals. J. Physiol. 557:207-228

Synapse in Xenopus 
Nerve-muscle cell culture

Freeze-etch of frog nmj