Curriculum
Vitae
Research Summary
Dr. Qu’s general
research interest is to apply dynamical theories to biological
systems at the systems level. The specific research areas are:
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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 sub-cellular compartment
whole cell multi-cellular tissue 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 heart.
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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.
Representative
Publications
Zhilin Qu,
Alan Garfinkel, Peng-Sheng Chen, James N. Weiss: Mechanisms of
discordant alternans and induction of reentry in a simulated cardiac
tissue. Circulation 102, 1664-1670(2000).
Ohara, T,
Zhilin
Qu, Lee M-H, Ohara K, Omichi C, Mandel WJ, Chen P-S,
Karagueuzian HS: Increased Vulnerability to Inducible Atrial
Fibrillation Caused by partial cellular uncoupling with heptanol.
Am. J. Physiol. 283, H1116-H1122 (2002).
Ling Yang, Robb
MacLellan, Zhangang Han, James N. Weiss, Zhilin Qu:
Multi-site phosphorylation and network dynamics of cyclin-dependent
kinase signaling in the eukaryotic cell cycle. Biophys. J.
86, 3432-3443 (2004).
Fagen Xie,
Zhilin
Qu, Junzhong Yang, James N. Weiss, and Alan Garfinkel: A
simulation study of the effects of cardiac anatomy in ventricular
fibrillation. J. Clin. Invest. 113, 686-693 (2004).
Zhilin Qu,
James N. Weiss and Robb MacLellan: Coordination of cell growth and
cell division: a mathematical modeling study. J. Cell Sci.
117, 4199(2004).
Zhangang Han, Ling
Yang, Robb MacLellan, James N. Weiss, Zhilin Qu: Hysteresis
and Cell cycle transitions: How crucial is it? Biophys. J.
88, 1626-1634(2005).
Zhilin Qu: The
critical mass hypothesis revisited: the effect of dynamical wave
stability on spontaneous termination of cardiac fibrillation, Am.
J. Physiol. 290, H255-263 (2006).
James N. Weiss, Alain
Karma, Peng-Sheng Chen, Alan Garfinkel, Zhilin Qu: From
pulsus to pulseless – the saga of cardiac alternans, Circ. Res.
98, 1244-1253 (2006).
Ling Yang, Zhangang
Han, W. Robb MacLellan, James N. Weiss, Zhilin Qu: Linking
cell division to cell growth in a spatiotemporal model of the cell
cycle. J. Theor. Biol. 2006 (in press)
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