Ronghua Zhuge PhD
|Institution||University of Massachusetts Medical School|
|Department||Microbiology and Physiological Systems|
|Address||University of Massachusetts Medical School|
55 Lake Avenue North
Worcester MA 01655
|Institution||UMMS - Graduate School of Biomedical Sciences|
1983, B.S.,Zhejiang University
1995, 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 (i.e., urinary 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 health and disease.
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.
A Postdoctoral Position is available tostudy in this laboratory. Contact Dr. ZhuGe for additional details firstname.lastname@example.org
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