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Faculty
 Lixia Yue
Assistant Professor of Cell Biology
Center for Cardiology and Cardiovascular Biology
lyue@uchc.edu
- Ph.D., McGill University
- Post Doctoral Fellow: HHMI, Children's Hospital (Boston), Harvard
Medical School
- Cell Biology Graduate
Program
- Accepting Lab Rotation Students: Summer '08, Fall '08,
Spring '09
Areas of Interest:
We are interested in Ca2+ signaling mechanisms and their potential
roles under physiological and pathological conditions. Calcium is the
most common signal transduction element in virtually all cells ranging
from bacteria to neurons. Recent studies have demonstrated the
importance of transient receptor potential (TRP) channels in mediating
calcium signals. The mammalian TRP channel superfamily consists of a
diverse group of Ca2+ permeable nonselective cation channels that may
play a role in pain transduction, thermo-sensation, mechanotransduction,
tumor suppression, vasodilatation, and neurodegenerative disorder. More
than 25 mammalian TRP channel genes have been cloned since the first TRP
channel protein was identified in Drosophila, yet their physiological
functions are to be revealed.
We apply a multi-disciplinary approach to study the potential
physiological and pathological functions of the Ca2+-permeable TRP
channels. We use molecular biology and biochemistry approaches to
identify channel proteins and the associated partners; we use
patch-clamp to study channel functions and gating mechanisms; and we use
in vivo animal models with disrupted or modified channel genes to
investigate physiological or pathological functions of the TRP channels.
We currently focus on two major projects. First, we will investigate TRP
channels and Ca2+ signaling mechanisms in cardiac fibrogenesis. Cardiac
fibrosis is detrimental and is associated with a variety of heart
diseases including arrhythmia, hypertrophy, and heart failure. However,
Ca2+ signaling mechanism in cardiac fibrogenesis is unknown. This
project will reveal potential roles of TRP channels in mediating Ca2+
signals in the cardiac fibroblast’s proliferation, differentiation, and
fibrogenesis. Second, we are interested in the gating mechanisms and
physiological functions of TRPM7 and TRPM6, the two channel-kinase
proteins that exhibit both channel functions and protein kinase
activities.
Lab Rotation Projects:
Project #1: Potential physiological functions of TRPM7. We have
recently found that TRPM7 is abundantly expressed in the heart (Nat.
Cell. Biol. 2002). The goal of this project is to study how TRPM7
contributes to cardiac fibrogenesis, a pathological process that is
involved in a variety of heart diseases including hypertrophy, heart
failure and sudden cardiac death. For this project, the rotation student
will start with studying how TRPM7 affects cardiac fibroblasts’
proliferation and differentiation.
Project #2: Gating mechanisms of TRPM7. A recent study showed
that TRPM7 is responsible for neuronal cell death caused by anoxia. We
have found that TRPM7 activity can be dramatically potentiated by
ischemia related conditions (JGP, 2005. in press). This project is to
identify the amino acid residues which determine the permeability,
selectivity and gating mechanisms of TRPM7. Recombinant TRPM7 will be
expressed in over-expression system and site-directed mutagenesis will
be applied in this study. The ultimate goal of this project is to reveal
the mechanism by which TRPM7 contributes to ischemic neuronal cell death
and stroke.
Project #3: TRPV6 and Ca2+ signaling mechanism. TRPV6 (or
CaT1) is the most Ca2+ selective ion channel in the TRP superfamily
(Nature, 2001). Activation of TRPV6 requires lowered intracellular Ca2+
concentration. The objective of this project is to study how TRPM6 is
gated under physiological conditions and potential roles of TRPV6 in
Ca2+ signaling mechanism. Looking for interacting proteins with TRPV6
will be the first step for this project.
Selected Publications:
Li M, Jiang J, Yue L. Distinct properties between TRPM6 and TRPM7.
2005. In preparation.
Jiang J, Li M, Yue L. Potentiation of TRPM7 inward currents by protons.
Journal of General Physiology. 2005. In press.
Dessaint J, Yu W, Krause JE, Yue L. Yohimbine inhibits firing
activities of rat dorsal root ganglion neurons by blocking Na+ channels
and vanilloid VR1 receptors. Eur J Pharmacol. 2004; 6:485(1-3):11-20.
*Runnels L, *Yue L, Clapham D. The TRP-PLIK channel is inactivated by
PIP2 hydrolysis. Nature Cell Biology. 2002; 4(5):329-36. *Co-first
author
Yue L, Navarro B, Ren D, Clapham D. The cation selectivity filter of
the bacterial sodium channel, NaChBac. Journal of General Physiology.
2002; 120 (6): 845-53.
Yue L, Peng J-B, Hediger M A, Clapham D.E. CaT1 Manifests the pore
properties of the calcium release activated calcium channel. Nature.
2001; 410, 705 – 709. [see News and Views. Nature 2001 410:648-9].
*Ren D, *Navarro B, *Xu H, *Yue L, Shi Q, Clapham. A prokaryotic
voltage-gated sodium channel. Science. 2001; 294(5550):2372-5. [see News
and Views. Science 2001 294: 2306-2308]. *Co-first author.
Runnels L, Yue L, Clapham D. TRP-PLIK, a bifunctional protein with
kinase and ion channel activities (Originally published in Science
Express as 10.1126/science.1058519 on January 18, 2001). Science.
2001;291 (5506): 1043-1047.
Yue L, Wang Z, Rindt H, Nattel S. Molecular evidence for a role of
Shaw (Kv3) potassium channel subunits in potassium currents of dog
atrium. Journal of Physiology. 2000; 527 (3): 467-478.
Yue L, Feng J, Wang Z, Nattel S. Effects of ambasilide, quinidine,
flecainide and verapamil on ultra-rapid delayed rectifier potassium
currents in canine atrial myocytes. Cardiovasc Res. 2000
Apr;46(1):151-61.
Nattel S, Li D, Yue L. "Basic mechanisms of atrial fibrillation-very
new insights into very old ideas. Annual Review of Physiology. 2000; 62:
51-77.
Nattel S, Matthews C, De Blasio E, Han W, Li D, Yue, L.
Dose-dependence of 4-aminopyride concentrations and electrophysiological
effects in dogs: potential relevance to ionic mechanisms in vivo.
Circulation. 2000; 101 (10): 1179-1184. |
