Brian Perrino

Brian Perrino, Ph.D.

Associate Professor

Summary

The primary focus of my research is to generate a better understanding of how contractile agonists control the Ca2+ sensitization mechanisms in gastric smooth muscles that manage myosin light chain phosphorylation and adjust the smooth muscle mechanical responses that underlie motility responses. Here in the Dept. of Physiology & Cell Biology at the University of Nevada, Reno School of Medicine, we have developed effective methods of analyzing low abundance signaling proteins in smooth muscles by SDS-PAGE-western blotting, and more recently, by utilizing the high throughput, high sensitivity Wes system from ProteinSimple, and have developed in situ PLA imaging to analyze protein phosphorylation and protein-protein interactions in cryostat sections from gastric smooth muscles. Using human gastric muscles from patients undergoing weight loss surgery, we are now investigating how gastric prokinetics might improve gastric motility be examining how these compounds affect basal CPI-17 and MYPT1 phosphorylation. Increasing basal CPI-17 and MYPT1 phosphorylation would inhibit myosin phosphatase, increase myosin light chain phosphorylation, and augment agonist-evoked contractions. Analyses of the intracellular phosphorylation-dependent signaling pathways in smooth muscles will generate a more complete under-standing of how gastric motor function is generated. These studies may help in developing novel therapeutics for patients suffering from functional dyspepsia and diabetic gastroparesis.

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  • Gastrointestinal

Selected publications

2015

  • An C, Bhetwal BP, Sanders KM, Somlyo AV, Perrino BA. 2015. Telokin phosphorylation and modulation of murine gastric fundus smooth muscle mechanical responses. manuscript under review, PLoS One.

2014

  • Sanders KM, Salter, AK, Hennig GW, Koh SD, Perrino BA, Ward, SM, and Baker, SA. 2014. Responses to enteric motor neurons in the gastric fundus of mice with reduced intramuscular interstitial cells of Cajal. Journal of Neurogastroenterology and Motility. 20:171-84.

2013

  • Bhetwal BP, Sanders KM, An C, Trappanese DM, Moreland RS, Perrino BA. 2013. Ca2+ sensitization pathways accessed by cholinergic neurotransmission in the murine gastric fundus. Journal of Physiology. 591.12:2971-86. Editor’s choice.
  • Bhetwal BP, An C, Baker SA, Lyon KL, Perrino BA. 2013. Impaired contractile responses and altered expression and phosphorylation of Ca2+ sensitization proteins in gastric antrum smooth muscles from ob/ob mice. The Journal of Muscle Research and Cell Motility. 34(2):137-49.

2012

  • Fu K, Mende Y, Bhetwal BP, Baker S, Perrino BA, Wirth B, Fisher SA. 2012. Tra2β protein is required for tissue specific splicing of a smooth muscle myosin phosphatase targeting subunit alternative exon. Journal of Biological Chemistry. 287(20):16575-85.

2011

  • Bhetwal BP, An CL, Fisher SA, Perrino BA. 2011. Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles. Neurogastroenterology & Motility. 23(10):e425-36.
  • Perrino BA. 2011. Regulation of gastrointestinal motility by Ca2+/calmodulin-stimulated protein kinase II. Archives of Biochemistry and Biophysics. 510(2):174-81.

2010

  • Qureshi S, Song J, Lee HT, Koh SD, Hennig GW, Perrino BA. 2010. CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS-colitis. Neurogastroenterology & Motility. 22(2):186-95, e64.

2009

  • Orie NN, Thomas AM, Perrino BA, Tinker A, Clapp LH. 2009. Ca2+/calcineurin regulation of cloned vascular K ATP channels: crosstalk with the protein kinase A pathway. British Journal of Pharmacology. 157(4):554-64.
  • Ayon R, Sones W, Forrest AS, Wiwchar M, Valencik ML, Sanguinetti AR, Perrino BA, Greenwood IA, Leblanc N. 2009. Complex phosphatase regulation of Ca2+-activated Cl-currents in pulmonary arterial smooth muscle cells. Journal of Biological Chemistry. 284(47):32507-21.

2008

  • Kim M, Hennig GW, Park K, Han IS, Smith TK, Koh SD, Perrino BA. 2008. Modulation of murine gastric antrum smooth muscle STOC activity and excitability by phospholamban. Journal of Physiology. 586 (Pt20): 4977-91.
  • Kim M, Hennig GW, Smith TK, Perrino BA. 2008. Phospholamban knockout increases CaM kinase II activity and intracellular Ca2+ wave activity and alters contractile responses of murine gastric antrum. Cell Physiology - American Journal of Physiology. 294(2):C432-41.
  • Chen J, Chen H, Sanders KM, Perrino BA. 2008. Regulation of SRF/CArG-dependent gene transcription during chronic partial obstruction of murine small intestine. Neurogastroenterology & Motility. 20(7):829-42. [ Editorial Viewpoint: MacDonald JA. 2008. Smooth muscle phenotypic plasticity in mechanical obstruction of the small intestine. Neurogastroenterology & Motility. 20(7): 737-40. ].

2007

  • Kim, M., and Perrino, B.A. 2007. CaM kinase II activation and phospholamban phosphorylation by SNP in murine gastric antrum smooth muscles. American Journal of Physiology-Gastrointestinal and Liver Physiology. 292.g1045-54.
  • Jabr, R.I., R.I., Wilson, A.J., Riddervold, M.H., Jenkins, A.H., Perrino, B.A., and Clapp. 2007. Nuclear translocation of calcineurin Ab but not Aa by platelet-derived growth factor in rat aortic smooth muscle. American Journal of Physiology - Cell Physiology. 292:C2213-25.

2006

  • Gary-Gouy, H., Sainz-Perez, A., Bismuth, G., Ghadiri, A., Perrino, B.A., and Dalloul, A. 2006. Cyclosporin-A inhibits ERK phosphorylation in B cells by modulating the binding of Raf protein to Bcl2. Biochemical and Biophysical Research Communications 344:134-139.
  • Hicks, G., Perrino, B.A., Marrion, N.V. 2006. Inhibition of BKCa channel activity by association with calcineurin in rat brain. European Journal of Neuroscience. 24:433-41.
  • Kim, M., Han, I.S., Koh, S.D., and Perrino, B.A. 2006. Role of CaM kinase II and phospholamban in SNP-induced relaxation of murine gastric fundus smooth muscle. The American Journal of Physiology - Cell Physiology. 291: C337-47.

2005

  • Kim, M., Cho, S.Y., Han, I.S., Koh, S.D., and Perrino, B.A. 2005. CaM kinase II and phospholamban contribute to caffeine-induced relaxation of murine gastric fundus smooth muscle. American Journal of Physiology - Gastrointestinal and Liver Physiology. 288:C1202-C1210.
  • Leblanc, N., Ledoux, J., Saleh, S., Sanguinetti, A., Angermann, J., O’Driscoll, K., Britton, F., Perrino, B.A., and Greenwood, I.A. 2005. Regulation of Calcium-Activated Chloride Channels in Smooth Muscle Cells–A Complex Picture Is Emerging. Canadian Journal of Physiology and Pharmacology. 83:541-546.
  • Sergeant, G.P., Ohya, S., Rehill, J.R., Perrino, B.A., Koh, S.D., Sanders, K.M., and Horowitz, B. 2005. Regulation of Kv4.3 channels by Ca2+/calmodulin-dependent protein kinase II. The American Journal of Physiology - Cell Physiology. 288:C304-C313.

2004

  • Greenwood, I.A., Ledoux, J., Perrino, B.A., and Leblanc, N. 2004. Calcineurin-dependent dephosphorylation augments IClCa in pulmonary artery smooth muscle cells. Journal of Biological Chemistry. 279:38830-38837.

2002

  • Riddervold, M.H., Lorenz, J.M., Beckett, E.A.H., Baker, S.A., and Perrino, B.A. 2002. Differential autophosphorylation of Ca2+/calmodulin-dependent protein kinase II from phasic and tonic smooth muscle tissues. American Journal of Physiology - Cell Physiology. 283: C1399-C1413.
  • Perrino, B.A., Wilson, A.J., Ellison, P., and Clapp, L.H. 2002. Substrate selectivity and sensitivity to inhibition by immunophilin/immunosuppressant complexes of calcineurin heterodimers composed of the ? or ? catalytic subunit. European Journal of Biochemistry. 269:3540-3548.

2001

  • Martin, B.A.; Oxhorn, B.C.; Rossow, C.R.; and Perrino, B.A. 2001. A cluster of basic residues in calcineurin B participates in the binding of calcineurin to phosphatidylserine vesicles. Journal of Biochemistry. (Tokyo)129:843-849.
  • Perrino, B.A. and Martin, B.A. 2001. Ca2+-and myristoylation-dependent association of calcineurin with phosphatidylserine. Journal of Biochemistry. (Tokyo)129:835-841.
  • Amberg, G., Koh, S.D., Perrino, B.A., Hatton, W.J., and Sanders, K.M. 2001. Regulation of A-type potassium channels in murine colonic myocytes by phosphatase activity. American Journal of Physiology - Cell Physiology. 281:C2020-2028.

2000

  • Perrino, B.A. 2000. Regulation of calcineurin-dependent signaling pathways by protein targeting. Recent Research Developments in Endocrinology. 1:209-232.

1999

  • Koh, S. D.; Perrino, B. A.; Hatton, W. J.; Kenyon, J. L.; and Sanders, K. M. 1999. Novel regulation of the A-type current in murine proximal colon by calcium/calmodulin-dependent protein kinase II. Journal of Physiology. 517 (Part1):75-84.
  • Perrino, B.A. 1999. Regulation of calcineurin phosphatase activity by its autoinhibitory domain. Archives of Biochemistry and Biophysics. 372:159-165.

1998

  • Perrino, B.A. and Soderling, T.R. 1998. Biochemistry and Pharmacology of the Calmodulin-Regulated Phosphatase Calcineurin. Invited chapter for “Calmodulin and Signal Transduction”, Academic Press, Eds: Linda van Eldik and D. Martin Watterson. 169-236.

Education

  • PhD, Cell Biology, Boston University, 1989
  • BS, Biology, Syracuse University