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)

Novel signal transduction pathways in smooth muscles that regulate contractility and impact diseases of the vasculature, airway and gastrointestinal tract.

Research Description

Our goal is to identify and characterize the function of molecules participating in signal transduction pathways that modulate contractility of smooth muscle (SM) both in adult tissues and smooth muscle cells that migrate.We continue our long term interests in the basic properties of the contractile apparatus and myosin crossbridges that reflect the special SM phenotype. Our laboratory was amongst the first to recognize the involvement of the small GTPase RhoA, it’s coupling to G-proteins coupled receptors and its ability to increase myosin regulatory light chain phosphorylation and force through inhibition of myosin phosphatase, and coined the term Ca2+ sensitization. Our current goal is to understand the physiological relevance, structure/function relationships and the mechanism of activation of the many RhoA GTP exchange factors (GEFS) and GTP activating proteins (GAPs) in SM, their crosstalk and their coupling to the plethora of agonists that stimultae SM, through different G-protein coupled receptors. These molecules may serve as more selective targets for therapies.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. Ultimately, the search for the basis of hypertension, atherosclerosis and other diseases of the vasculature drive the research.

Selected Publications

  • Lakshmikanthan S, Zieba B, Ge Z, Momotani K, Zheng X, Lund H, Artamonov M, Maas J, Szabo A, Zhang D, Auchampach J, Mattson D, Somlyo A, Chrzanowska-Wodnicka M. Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure. Arteriosclerosis, thrombosis, and vascular biology. 2014;34(7): 1486-94. PMID: 24790136
  • Artamonov M, Momotani K, Utepbergenov D, Franke A, Khromov A, Derewenda Z, Somlyo A. The p90 ribosomal S6 kinase (RSK) is a mediator of smooth muscle contractility. PloS one. 2013;8(3): e58703. PMID: 23516539 | PMCID: PMC3596281
  • 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
  • Derewenda U, Oleksy A, Stevenson A, Korczynska J, Dauter Z, Somlyo A, Otlewski J, Somlyo A, Derewenda Z. The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle. Structure (London, England : 1993). 2004;12(11): 1955-65. PMID: 15530360
  • Somlyo A, Somlyo A. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiological reviews. 2003;83(4): 1325-58. PMID: 14506307
  • Wei Y, Zhang Y, Derewenda U, Liu X, Minor W, Nakamoto R, Somlyo A, Somlyo A, Derewenda Z. Crystal structure of RhoA-GDP and its functional implications. Nature structural biology. 1997;4(9): 699-703. PMID: 9302995
  • Gong M, Iizuka K, Nixon G, Browne J, Hall A, Eccleston J, Sugai M, Kobayashi S, Somlyo A, Somlyo A. Role of guanine nucleotide-binding proteins--ras-family or trimeric proteins or both--in Ca2+ sensitization of smooth muscle. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(3): 1340-5. PMID: 8577766 | PMCID: PMC40082
  • Somlyo A, Somlyo A. Signal transduction and regulation in smooth muscle. Nature. 1994;372(6503): 231-6. PMID: 7969467
  • Somlyo A, Bond M, Somlyo A, Scarpa A. Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proceedings of the National Academy of Sciences of the United States of America. 1985;82(15): 5231-5. PMID: 2991913 | PMCID: PMC390534
  • Somlyo A, Butler T, Bond M, Somlyo A. Myosin filaments have non-phosphorylated light chains in relaxed smooth muscle. Nature. 1981;294(5841): 567-9. PMID: 6895544