Dr. Qu’s general research
interest is to apply dynamical theories to biological systems at the systems
level. The specific research areas are:
- Multi-scale modeling
of cardiac excitation-contraction coupling and arrhythmias. Ventricular
fibrillation (VF) is the leading cause of sudden cardiac death and the only
effective therapy is implantable cardioverter-defibrillators but expensive and
limited in availability worldwide. Developing new effective and economic
anti-arrhythmic drugs and improving the efficacy of defibrillators are
apparently attractive therapeutic strategies, which need a better understanding
of the mechanisms of VF. The cardiac system is extremely complex with nonlinear
interactions, involving many levels of regulation: ion channel à sub-cellular compartment à whole cell à multi-cellular tissue à anatomical heart. Combined with experiments, computer
modeling at all different levels and theories developed according to nonlinear
dynamics are critically useful for the understanding of the mechanisms of VF
and thus for the development of novel therapeutics. My goal is to develop an
integrated computational system with multiple scales of regulation to
understand the excitation-contraction coupling and arrhythmogenesis in the
- Dynamics of cardiac
metabolism. Cell metabolism is regulated by a complex network which not only
controls the energy demand for the cell but can also generate dynamics to
trigger cell death and arrhythmias. The initial research goal is to understand
the dynamics due to the coupling between the glycolytic cycle, the mitochondria
TCA cycle, and the SR/glycogenic cycle and their spatiotemporal dynamics
through mathematical modeling and computer simulation, and to provide
theoretical bases for how cardiac metabolism affects cardiac arrhythmogenesis
and cardioprotection against ischemic injury. The ultimate goal is to develop a
computational model system that will eventually include the interaction
networks of genes, proteins, and metabolites and link the dynamics of the
interactions to cardiac arrhythmogensis and mitochondria-related cell death.
- Cell cycle control
and biological signal transduction. Biological processes are regulated by
complex networks of genes, proteins, and metabolites. Although understanding
the functions of individual genes or proteins provides critical detailed
information, this reductionist approach normally favored by biologists has
limitations and it is far from understanding the whole system, since the
interactions between the building blocks are complex and nonlinear. Due to the
complexity, intuition has limited capability for synthesizing all of the
information gathered from the biological experiments into a cohesive holistic
understanding of the system behavior. Computer modeling and complex system
theory become more and more important for understanding the behaviors of signal
transduction networks in biology. I will use cell cycle control as a specific
working example but I am also interested in generic dynamics arising from
biological signal transduction network.
- Nivala M., Korge P., Nivala M., Weiss J.N., Qu Z., “Linking flickering to waves and whole-cell oscillations in a mitochondrial network model,” Biophys J. 2011 Nov 2;1010(9):2102-22. Epub 2011 Nov 1.
- Madhavni R.V., Xie Y., Pantazis A., Garfinkel A., Qu Z., Weiss J.N., Olcese R., “Shaping a new Ca2+ conductance to suppress early afterdepolarizations in cardiac myocytes,” J Physiol. 2011 Dec 15;589(Pt 24):6081-92. Epub 2011 Oct 24.
- Korge P., Yang L., Yang J.H., Wang Y. Qu Z., Weiss J.N., “Protective role of transient pore openings in calcium handling by cardiac mitochondria,” J Biol Chem. 2011 Oct 7;286(40):34851-7. Epub 2011 Aug 22.
- Chang M.G., Sato D., de Lange E., Lee J.H., Karagueuzian H.S., Garfinkel A., Weiss J.N., Qu Z., “Bi-stable wave propagation and early afterdepolarization-mediated cardiac arrhythmias,” Heart Rhythm. 2012 Jan;9(1):115-22. Epub 2011 Aug 17.
- Qu Z., Garfinkel A., Weiss J.N., Nivala M., “Multi-scale modeling in biology: how to bridge the gaps between scales?” Prog Biophys Mol Biol. 2011 Oct;107(1):21-31. Epub 2011 Jun 23.
- Qu Z., Xie Y., Garfinkel A., Weiss J.N., “T-wave alternans and arrhythmogenesis in cardiac diseases,” Front Physiol. 2010;1:154.
- Morita N., Lee J.H., Xie Y., Sovari A., Qu Z., Weiss J.N., karagueuzian H.S., “Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine,” J Am Coll Cardiol. 2011 Jan 18;57(3):366-75.
- Weiss J.N., Nivala M., Garfinkel A. Qu Z., “Alternans and arrhythmias: from cell to heart,” Circ Res. 2011 Jan 7;108(1):98-112. Review.
- Baher A.A., Uy M., Xie F., Garfinkel A., Qu Z., Weiss J.N., “Bidirectional ventricular tachycardia: ping pong in the His-Purkinje system,” Heart Rhythm. 2011 Apr;8(4)599-605. Epub 2010 Nov 29.
- Qu Z., “Chaos in the genesis and maintenance of cardiac arrhythmias,” Prog Biophys Mol Biol. 2011 May;105(3):247-57. Epub 2010 Nov 13. Review.