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Ronghua ZhuGe PhD

TitleAssociate Professor
InstitutionUniversity of Massachusetts Medical School
DepartmentMicrobiology and Physiological Systems
AddressUniversity of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-3793
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentNeuroscience


    Collapse Overview 
    Collapse overview

    Academic Background  

    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 (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).

     



    Collapse 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.



    Collapse Post Docs

    Postdoctoral Positions are available in this laboratory. Contact Dr. ZhuGe for additional details at ronghua.zhuge@umassmed.edu

     




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Wang P, Zhao W, Sun J, Tao T, Chen X, Zheng YY, Zhang CH, Chen Z, Gao YQ, She F, Li YQ, Wei LS, Lu P, Chen CP, Zhou J, Wang DQ, Chen L, Shi XH, Deng L, ZhuGe R, Chen HQ, Zhu MS. 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. J Allergy Clin Immunol. 2018 Apr; 141(4):1259-1268.e11. PMID: 28754608.
      View in: PubMed
    2. Zheng K, Lu P, Delpapa E, Bellve K, Deng R, Condon JC, Fogarty K, Lifshitz LM, Simas TAM, Shi F, ZhuGe R. Bitter taste receptors as targets for tocolytics in preterm labor therapy. FASEB J. 2017 May 30. PMID: 28559440.
      View in: PubMed
    3. Keeler AM, Liu D, Zieger M, Xiong L, Salemi J, Bellve K, Byrne BJ, Fuller DD, ZhuGe R, ElMallah MK. Airway smooth muscle dysfunction in Pompe (Gaa-/-) mice. Am J Physiol Lung Cell Mol Physiol. 2017 Mar 23; ajplung.00568.2016. PMID: 28336814.
      View in: PubMed
    4. Lu P, Zhang CH, Lifshitz LM, ZhuGe R. Extraoral bitter taste receptors in health and disease. J Gen Physiol. 2017 Jan 04. PMID: 28053191.
      View in: PubMed
    5. Zhang CH, Wang P, Liu DH, Chen CP, Zhao W, Chen X, Chen C, He WQ, Qiao YN, Tao T, Sun J, Peng YJ, Lu P, Zheng K, Craige SM, Lifshitz LM, Keaney JF, Fogarty KE, ZhuGe R, Zhu MS. The molecular basis of the genesis of basal tone in internal anal sphincter. Nat Commun. 2016 Apr 22; 7:11358. PMID: 27101932.
      View in: PubMed
    6. Lefkowitz JJ, DeCrescenzo V, Duan K, Bellve KD, Fogarty KE, Walsh JV, ZhuGe R. Catecholamine exocytosis during low frequency stimulation in mouse adrenal chromaffin cells is primarily asynchronous and controlled by the novel mechanism of Ca2+ syntilla suppression. J Physiol. 2014 Nov 1; 592(21):4639-55. PMID: 25128575.
      View in: PubMed
    7. Zhang CH, Lifshitz LM, Uy KF, Ikebe M, Fogarty KE, ZhuGe R. The cellular and molecular basis of bitter tastant-induced bronchodilation. PLoS Biol. 2013; 11(3):e1001501. PMID: 23472053.
      View in: PubMed
    8. Zhang CH, Li Y, Zhao W, Lifshitz LM, Li H, Harfe BD, Zhu MS, ZhuGe R. The transmembrane protein 16A Ca(2+)-activated Cl- channel in airway smooth muscle contributes to airway hyperresponsiveness. Am J Respir Crit Care Med. 2013 Feb 15; 187(4):374-81. PMID: 23239156.
      View in: PubMed
    9. Zhang CH, Chen C, Lifshitz LM, Fogarty KE, Zhu MS, ZhuGe R. Activation of BK channels may not be required for bitter tastant-induced bronchodilation. Nat Med. 2012 May 04; 18(5):648-50; author reply 650-1. PMID: 22561814.
      View in: PubMed
    10. Lifshitz LM, Carmichael JD, Lai FA, Sorrentino V, Bellvé K, Fogarty KE, ZhuGe R. Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca(2+) sparks in airway myocytes. J Gen Physiol. 2011 Aug; 138(2):195-209. PMID: 21746845.
      View in: PubMed
    11. Zhuge R, Bao R, Fogarty KE, Lifshitz LM. Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle. J Biol Chem. 2010 Jan 15; 285(3):2203-10. PMID: 19920135.
      View in: PubMed
    12. Lefkowitz JJ, Fogarty KE, Lifshitz LM, Bellve KD, Tuft RA, ZhuGe R, Walsh JV, De Crescenzo V. Suppression of Ca2+ syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells. J Gen Physiol. 2009 Oct; 134(4):267-80. PMID: 19786582.
      View in: PubMed
    13. Bao R, Lifshitz LM, Tuft RA, Bellvé K, Fogarty KE, ZhuGe R. 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. J Gen Physiol. 2008 Jul; 132(1):145-60. PMID: 18591421.
      View in: PubMed
    14. De Crescenzo V, Fogarty KE, Zhuge R, Tuft RA, Lifshitz LM, Carmichael J, Bellvé KD, Baker SP, Zissimopoulos S, Lai FA, Lemos JR, Walsh JV. Dihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals. J Neurosci. 2006 Jul 19; 26(29):7565-74. PMID: 16855084.
      View in: PubMed
    15. ZhuGe R, DeCrescenzo V, Sorrentino V, Lai FA, Tuft RA, Lifshitz LM, Lemos JR, Smith C, Fogarty KE, Walsh JV. Syntillas release Ca2+ at a site different from the microdomain where exocytosis occurs in mouse chromaffin cells. Biophys J. 2006 Mar 15; 90(6):2027-37. PMID: 16387759.
      View in: PubMed
    16. Zhuge R, Fogarty KE, Baker SP, McCarron JG, Tuft RA, Lifshitz LM, Walsh JV. 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. Am J Physiol Cell Physiol. 2004 Dec; 287(6):C1577-88. PMID: 15306542.
      View in: PubMed
    17. De Crescenzo V, ZhuGe R, Velázquez-Marrero C, Lifshitz LM, Custer E, Carmichael J, Lai FA, Tuft RA, Fogarty KE, Lemos JR, Walsh JV. Ca2+ syntillas, miniature Ca2+ release events in terminals of hypothalamic neurons, are increased in frequency by depolarization in the absence of Ca2+ influx. J Neurosci. 2004 Feb 4; 24(5):1226-35. PMID: 14762141.
      View in: PubMed
    18. Zhuge R, Fogarty KE, Tuft RA, Walsh JV. 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. J Gen Physiol. 2002 Jul; 120(1):15-27. PMID: 12084772.
      View in: PubMed
    19. ZhuGe R, Fogarty KE, Tuft RA, Lifshitz LM, Sayar K, Walsh JV. Dynamics of signaling between Ca(2+) sparks and Ca(2+)- activated K(+) channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca(2+) current. J Gen Physiol. 2000 Dec; 116(6):845-64. PMID: 11099351.
      View in: PubMed
    20. ZhuGe R, Tuft RA, Fogarty KE, Bellve K, Fay FS, Walsh JV. The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and spontaneous transient outward currents in single smooth muscle cells. J Gen Physiol. 1999 Feb; 113(2):215-28. PMID: 9925820.
      View in: PubMed
    21. ZhuGe R, Sims SM, Tuft RA, Fogarty KE, Walsh JV. Ca2+ sparks activate K+ and Cl- channels, resulting in spontaneous transient currents in guinea-pig tracheal myocytes. J Physiol. 1998 Dec 15; 513 ( Pt 3):711-8. PMID: 9824712.
      View in: PubMed
    22. ZhuGe R, Li S, Chen TH, Hsu WH. Alpha2-adrenergic receptor-mediated Ca2+ influx and release in porcine myometrial cells. Biol Reprod. 1997 May; 56(5):1343-50. PMID: 9160737.
      View in: PubMed
    23. Zhuge R, Hsu WH. The caffeine- and ryanodine-sensitive Ca++ store in porcine myometrial cells: its heterogeneity of all-or-none Ca++ release. J Pharmacol Exp Ther. 1995 Dec; 275(3):1077-83. PMID: 8531066.
      View in: PubMed
    24. Zhuge R, Li S, Chen TH, Hsu WH. Oxytocin induced a biphasic increase in the intracellular Ca2+ concentration of porcine myometrial cells: participation of a pertussis toxin-insensitive G-protein, inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, and Ca2+ channels. Mol Reprod Dev. 1995 May; 41(1):20-8. PMID: 7619502.
      View in: PubMed
    25. Yu H, Zhuge R, Hsu WH. Lysine vasopressin-induced increases in porcine myometrial contractility and intracellular Ca2+ concentrations of myometrial cells: involvement of oxytocin receptors. Biol Reprod. 1995 Mar; 52(3):584-590. PMID: 7756452.
      View in: PubMed
    26. ZhuGe R, Li S, Lee B, Hsu WH. Characterization of freshly dispersed porcine myometrial cells: evidence for voltage-dependent Ca2+ channels and regulatory receptors. J Reprod Fertil. 1994 Sep; 102(1):49-55. PMID: 7799325.
      View in: PubMed
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