Avril V. Somlyo, Ph.D.

Professor of Pathology and Physiology

RESEARCH:

Our goal is to understand the signal transduction pathways and the mechanisms of regulation of the contractile proteins leading to contraction or relaxation in normal vascular smooth muscle. Mechanical measurements and photolysis of caged nucleotides are utilized to characterize the kinetics of the mechanical motors or cross-bridges in small muscle bundles. A second major area of research involves light (laser scanning confocal microscopy) and electron optical methods for studies of the structural aspects of cellular signal transduction and ion transport. Electron probe x-ray microanalysis provides compositional information, at high spatial resolution, and addresses questions concerning intracellular transport across cell organelles in situ and the role of membrane-associated calcium. Ultimately, the search for the basis of hypertension, atherosclerosis and other diseases of the vasculature drive the research. Website at www.med.virginia.edu/som-bas/physio.

REFERENCES:

  • Somlyo AV, Bradshaw D, Ramos S. Murphy C. Myers CE, Somlyo AP: Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells. Biochem Biophys Res Commun 2000; 269: 652-659.
  • Read PW, Liu X, Longenecker K, Dipierro CG, Walker LA, Somlyo AV, Somlyo AP, Nakamoto RK: Human RhoA/RhoGDI complex expressed in yeast: GTP exchange is sufficient for translocation of RhoA to liposomes.
  • Shao Z, Shi D, Somlyo AV: Cryoatomic force microscopy of filamentous actin. Biopsy J 2000; 78: 950-958.
  • Somlyo AP, Somlyo AV: Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol (Lond) 2000; 522: 177-185.
  • Longenecker K, Read P, Derewenda U, Dauter Z, Liu X, Garrard S, Walker L, Somlyo AV, Nakamoto RK, Somlyo AP, Derewenda ZS: How RhoGDI binds Rho. Acta Crystallogr D Biol Crystallogr 1999; 55: 1503-1515.
  • Nguyen DH, Catling AD,Webb DJ, Sankovic M, Walker LA, Somlyo AV, Weber MJ, Gonias SL: Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J Cell Biol 1999; 146: 149-164.
  • Somlyo AP, Wu X, Walker LA, Somlyo AV: Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and phosphatases. Rev Physiol Biochem Pharmacol 1999; 134: 201-234.
  • Somlyo AP, Somlyo AV: From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol Scand 1998; 164: 437-448.
  • Somlyo AV, Matthew JD, Wu X, Khromov AS, Somlyo AP: Regulation of the cross-bridge cycle: the effects of MgADP, LC17 isoforms and telokin. Acta Physiol Scand 1998; 164: 381-388.
  • Fu X, Gong MC, Jia T, Somlyo AV, Somlyo AP: The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+sensitization of smooth muscle. FEBS Lett 1998; 440: 183-187.
  • He ZH, Ferenczi MA, Brune M, Trentham DR, Webb MR, Somlyo AP, Somlyo AV: Time-resolved measurements of phosphate release by cycling cross-bridges in portal vein smooth muscle. Biophys J 1998; 75: 3031-3040.
  • Matthew JD, Khromov AS, Trybus KM, Somlyo AP, Somlyo AV: Myosin essential light chain isoforms modulate the velocity of shortening propelled by nonphosphorylated cross-bridges. J Biol Chem 1998; 273: 31289-31296.
  • Khromov AS, Somlyo AV, Somlyo AP: Thiophosphorylation of myosin light chain increases rigor stiffness of rabbit smooth muscle. J Physiol (Lond) 1998; 512: 345-350.
  • Khromov A, Somlyo AV, Somlyo AP: MgADP promotes a catch-like state developed through force-calcium hysteresis in tonic smooth muscle. Biophys J 1998; 75: 1926-1934.
  • Walker LA, Gailly P, Jensen P, Somlyo AV, Somlyo AP: The unimportance of being (protein kinase C) epsilon. FASEB J 1998; 12:813-821.
  • Wu X, Haystead TA, Nakamoto RK, Somlyo AV, Somlyo AP: Acceleration of myosin light chain dephosphorylation and relaxation of smooth muscle by telokin. Synergism with cyclic nucleotide-activated kinase. J Biol Chem 1998; 273: 11362-11369.
  • Horikawa Y, Goel A, Somlyo AP, Somlyo AV: Mitochondrial calcium in relaxed and tetanized myocardium. Biophys J 1998; 74: 1579-1590.
  • Lesh RE, Nixon GF, Fleischer S, Airey JA, Somlyo AP, Somlyo AV: Localization of ryanodine receptors in smooth muscle. Circ Res 1998; 82:175-185.