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One or more keywords matched the following properties of ZhuGe, Ronghua
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Academic Background  

B.S.,Zhejiang University
Ph.D., Iowa State University

Smooth Muscle in Health and Disease 


Smooth muscle, lining along the walls of virtually all hollow organs, plays pivotal roles in physiological functions such as maintaining blood pressure and regulating bronchial tone. Defects in this type of cell cause congenital and acquired pathological conditions such as hypertension and asthma.Intracellular calcium is a primary signal in mediating smooth muscle function, and ion channels and G-protein coupled receptors are the major molecules to regulate the calcium level in smooth muscle. Research in our laboratory is focused on acquiring a quantitative understanding of the ways Ca² signals, ion channel and receptor activities are controlled and regulated in smooth muscle.Our methods include patch-clamp, intracellular Ca2+ concentration measurement, 2D and 3D visualization of cellular distribution of proteins, in vitro bioassays, molecular biology, computer modeling, animal models of diseases, transgenic knock-in and knock-out mouse models, and high-speed (>500 Hz) wide-field microscopy developed by the Biomedical Imaging Group (http://invitro.umassmed.edu/).

We have been studying highly localized, short-lived Ca2+ transients (Ca2+ sparks) that result from the opening of a few clustered ryanodine receptors (RyRs) in the membrane of sarcoplasmic reticulum (SR). These local Ca2+ signals are the elementary events of precipitating global changes of Ca2+ in striated muscles and neurons. In smooth muscle from airways, corpora cavernosa, and some blood vessels, Ca2+ sparks act in their own right to turn on a cluster of big-conductance Ca2+-activated K+ (BK) channels and Ca2+-activated Cl- (Cl(Ca)) channels in the vicinity of release sites (See Fig. 1)

Activation of these two types of channels produces spontaneous transient outward currents (STOCs) and spontaneous transient inward currents (STICs), respectively, which in turn regulate the activities of Ca2+-permeable channels.We recently discovered that Ca2+ sparks function as stabilizers of membrane potential and control the contractile state of airway smooth muscle, and Cl(Ca) channel TMEM16A is up-regulated in a mouse model of chronic asthma.  We aim to understand the mechanisms by which Ca2+ sparks activate the BK and TMEM16A Cl(Ca) channels, to investigate the structure and function of TMEM16A, and to determine the roles of Ca2+ spark signaling in asthma and other smooth muscle disorders (e.g., fecal incontinence).

A second area of our research is to understand the roles of G-protein coupled bitter taste receptors in regulating smooth muscle pathophysiology. Bitter taste, one of five basic taste qualities, guides organisms to avoid harmful toxins and noxious substances, and thus is critical to animal and human survival. It has long been thought that specialized epithelial cells in the taste buds of the tongue detect bitter tastant and initiate the sensation of bitterness.However, emerging evidence has gradually brought attention to cells in extraoral tissues where bitter tastants can generate different biological responses tailored to the location. We and others recently discovered that bitter tasting compounds relax airway smooth muscle more completely than the most commonly used bronchodilator ß2 agonists. Thus, We are interested in studying the cellular and molecular mechanisms by which bitter tasting compounds relax smooth muscle, and the roles of bitter taste receptors and their downstream signaling in controlling smooth muscle function in normal and disease states (e.g., asthma and preterm labor).

 

Rotation Projects

Rotation projects are available to study (1) the pathophysiology of Cl- channel TMEM16A in smooth muscle, (2) molecular mechanisms by which bitter tasting compounds relax smooth muscle, and (3) the role of bitter taste receptors in the pathogenesis of smooth muscle disorders.

Summary Focus: The ZhuGe lab studies the molecular mechanisms by which Ca2+ signals and ion channels control neurotransmitter release and smooth muscle contractility. We also exploit new physiological functions of bitter taste receptors in extra-oral tissues and organs. We aim to find novel molecular targets for new therapies to manage asthma, fecal incontinence, preterm labor and adenomyosis.
One or more keywords matched the following items that are connected to ZhuGe, Ronghua
Item TypeName
Academic Article Spontaneous transient outward currents arise from microdomains where BK channels are exposed to a mean Ca(2+) concentration on the order of 10 microM during a Ca(2+) spark.
Academic Article The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and spontaneous transient outward currents in single smooth muscle cells.
Academic Article Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca(2+) sparks in airway myocytes.
Academic Article Activation of BK channels may not be required for bitter tastant-induced bronchodilation.
Academic Article The transmembrane protein 16A Ca(2+)-activated Cl- channel in airway smooth muscle contributes to airway hyperresponsiveness.
Academic Article The cellular and molecular basis of bitter tastant-induced bronchodilation.
Academic Article Ca(2+) spark sites in smooth muscle cells are numerous and differ in number of ryanodine receptors, large-conductance K(+) channels, and coupling ratio between them.
Academic Article A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle.
Academic Article Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle.
Concept Muscle Contraction
Concept Muscle Relaxation
Concept Muscle, Smooth
Concept Muscle Hypotonia
Concept Myocytes, Smooth Muscle
Concept Muscle Cells
Concept Muscle, Skeletal
Academic Article The molecular basis of the genesis of basal tone in internal anal sphincter.
Academic Article Extraoral bitter taste receptors in health and disease.
Academic Article Airway smooth muscle dysfunction in Pompe (Gaa-/- ) mice.
Academic Article Bitter taste receptors as targets for tocolytics in preterm labor therapy.
Academic Article Inflammatory mediators mediate airway smooth muscle contraction through a G protein-coupled receptor-transmembrane protein 16A-voltage-dependent Ca2+ channel axis and contribute to bronchial hyperresponsiveness in asthma.
Academic Article Azithromycin inhibits muscarinic 2 receptor-activated and voltage-activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction.
Academic Article Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+ signaling, uterine contraction, gestation length, or litter size in mice?.
Academic Article Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.
Academic Article Genetic deletion of the Tas2r143/Tas2r135/Tas2r126 cluster reveals that TAS2Rs may not mediate bitter tastant-induced bronchodilation.
Academic Article TMEM16A in smooth muscle cells acts as a pacemaker channel in the internal anal sphincter.
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