Avril V. Somlyo

Education

  • MSc, University of Saskatchewan, Canada
  • PhD, University of Pennsylvania, PA

Primary Appointment

  • Professor, Molecular Physiology and Biological Physics

Contact

Research Interest(s)

Signaling pathways that regulate contractility in smooth muscle tissues and migrating cells in normal and disease states such an coronary artery disease, asthma and hypertension. Structure function studies of the intercalated disk in the heart.

Research Description

Our goal is to identify and characterize the function of molecules participating in signal transduction pathways that modulate contractility of smooth muscle both in adult tissues and smooth muscle cells that migrate, for example, during embryonic development to form the coronary vessels. Studies are carried out at the molecular, cellular, tissue and animal level in order to define the physiological or pathophysiological function of the signaling molecules under study. A particular focus is on regulation of myosin phosphatase activity through the small GTPase, RhoA and through cGMP kinase pathways which inhibit and activate this phosphatase, respectively. Apart from standard biochemical, molecular biological technologies and mouse models, other approaches include the photolysis of caged nucleotides and signaling molecules to characterize the regulation and the kinetics of the myosin motors responsible for force development, confocal microscopy and state of the art electron optical methods for studies of localization and translocation of signaling molecules as well as the structural aspects of cellular signal transduction. Electron probe X-ray microanalysis and electron energy loss analysis, which provide compositional information at high spatial resolution (5nm) are currently being applied to address the hypothesis that alteration of Ca2+ in the intercalated disk space leads to disruption of cadherins junctions and electrical conduction in the heart. Ultimately, the search for the basis of hypertension, atherosclerosis and other diseases of the vasculature, as well as the source of some arrhythmias in the heart, drive the research.

Selected Publications

  • Khromov A, Momotani K, Jin L, Artamonov M, Shannon J, Eto M, Somlyo A. Molecular mechanism of telokin-mediated disinhibition of myosin light chain phosphatase and cAMP/cGMP-induced relaxation of gastrointestinal smooth muscle. The Journal of biological chemistry. 2012;287(25): 20975-85. PMID: 22544752 | PMCID: PMC3375521
  • Momotani K, Somlyo A. p63RhoGEF: A New Switch for G(q)-Mediated Activation of Smooth Muscle. Trends in cardiovascular medicine. 2012;22(5): 122-7. PMID: 22902181 | PMCID: PMC3472095
  • Bielnicki J, Shkumatov A, Derewenda U, Somlyo A, Svergun D, Derewenda Z. Insights into the molecular activation mechanism of the RhoA-specific guanine nucleotide exchange factor, PDZRhoGEF. The Journal of biological chemistry. 2011;286(40): 35163-75. PMID: 21816819 | PMCID: PMC3186380
  • Hoofnagle M, Neppl R, Berzin E, Teg Pipes G, Olson E, Wamhoff B, Somlyo A, Owens G. Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes. American journal of physiology. Heart and circulatory physiology. 2011;300(5): H1707-21. PMID: 21357509 | PMCID: PMC3094091
  • Momotani K, Artamonov M, Utepbergenov D, Derewenda U, Derewenda Z, Somlyo A. p63RhoGEF couples Gα(q/11)-mediated signaling to Ca2+ sensitization of vascular smooth muscle contractility. Circulation research. 2011;109(9): 993-1002. PMID: 21885830 | PMCID: PMC3211138
  • Zieba B, Artamonov M, Jin L, Momotani K, Ho R, Franke A, Neppl R, Stevenson A, Khromov A, Chrzanowska-Wodnicka M, Somlyo A. The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. The Journal of biological chemistry. 2011;286(19): 16681-92. PMID: 21454546 | PMCID: PMC3089510
  • Jin L, Gan Q, Zieba B, Goicoechea S, Owens G, Otey C, Somlyo A. The actin associated protein palladin is important for the early smooth muscle cell differentiation. PloS one. 2010;5(9): e12823. PMID: 20877641 | PMCID: PMC2943901
  • Yoshida T, Gan Q, Franke A, Ho R, Zhang J, Chen Y, Hayashi M, Majesky M, Somlyo A, Owens G. Smooth and cardiac muscle-selective knock-out of Kruppel-like factor 4 causes postnatal death and growth retardation. The Journal of biological chemistry. 2010;285(27): 21175-84. PMID: 20439457 | PMCID: PMC2898332
  • Jin L, Hastings N, Blackman B, Somlyo A. Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury. Journal of muscle research and cell motility. 2009;30(1): 41-55. PMID: 19205907 | PMCID: PMC2852132
  • Jin L, Yoshida T, Ho R, Owens G, Somlyo A. The actin-associated protein Palladin is required for development of normal contractile properties of smooth muscle cells derived from embryoid bodies. The Journal of biological chemistry. 2008;284(4): 2121-30. PMID: 19015263 | PMCID: PMC2629081
  • Momotani K, Khromov A, Miyake T, Stukenberg P, Somlyo A. Cep57, a multidomain protein with unique microtubule and centrosomal localization domains. The Biochemical journal. 2008;412(2): 265-73. PMID: 18294141
  • Feng J, Somlyo A, Somlyo A, Shao Z. Automated electron tomography with scanning transmission electron microscopy. Journal of microscopy. 2007;228 406-12. PMID: 18045335
  • Jin L, Kern M, Otey C, Wamhoff B, Somlyo A. Angiotensin II, focal adhesion kinase, and PRX1 enhance smooth muscle expression of lipoma preferred partner and its newly identified binding partner palladin to promote cell migration. Circulation research. 2007;100(6): 817-25. PMID: 17322171
  • Gorenne I, Jin L, Yoshida T, Sanders J, Sarembock I, Owens G, Somlyo A, Somlyo A. LPP expression during in vitro smooth muscle differentiation and stent-induced vascular injury. Circulation research. 2006;98(3): 378-85. PMID: 16397143
  • Khromov A, Wang H, Choudhury N, McDuffie M, Herring B, Nakamoto R, Owens G, Somlyo A, Somlyo A. Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(7): 2440-5. PMID: 16461919 | PMCID: PMC1413704
  • Sinha S, Wamhoff B, Hoofnagle M, Thomas J, Neppl R, Deering T, Helmke B, Bowles D, Somlyo A, Owens G. Assessment of contractility of purified smooth muscle cells derived from embryonic stem cells. Stem cells (Dayton, Ohio). 2006;24(7): 1678-88. PMID: 16601077