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Thomas Jefferson University - Masumi Eto, Ph.D.
Masumi Eto, Ph.D.

Molecular Physiology and Biophysics
Associate Professor of Molecular Physiology and Biophysics
Member, Kimmel Cancer Center
Mailing Address
1020 Locust Street, 436 JAH
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-7891
Fax: 215-503-2073
masumi.eto@jefferson.edu
Qualifications
Ph. D., Hokkaido University, Chemistry, 1996
Expertise and Research Interests
>> SIGNAL TRANSDUCTION IN THE REGULATION OF CELL MOTILITY <<

RESEARCH OVERVIEW:

Regulation of cell motility is a fundamental process for every aspect in biology. The long-term goal of our research is to understand the regulatory circuits and rationales of the dysregulation of the process. Cellular stimulation, such as released chemical substances and physical stresses, triggers sequential activation and inhibition of multiple signaling molecules that drive reorganization of cytoskeletons, such as force generation, morphological change, transportation, and migration. Not surprisingly, dysfunctions in the cytoskeletal reorganization have been linked to various diseases, as well as served as a therapeutic target to normalize pathological situations.

A main focus of our research involves understanding the pathophysiology of smooth muscles, such as artery, airway, stomach, intestine and urinary bladder. Smooth muscle contraction/relaxation/proliferation are triggered in response to stimuli with a plethora of chemical substances and physical stresses, although the underlying mechanisms are largely unknown. Contractile malfunctions and remodeling of smooth muscle have been linked to various diseases, such as hypertension, asthma, gastroparesis, bowel diseases, and urinary dysfunctions. To develop new strategies for clinical interventions we must fully understand molecular basis of the signaling pathways regulating each smooth muscle. Furthermore, smooth muscle contraction is a synchronized process of actin-myosin regulation, which is a good model to solve the complexed process in cell motility. We use a multidisciplinary approach in protein chemistry, microscopy, molecular biology, structural biology and physiology for dissecting the signaling pathways at atomic, molecular, cellular, and in-vivo levels.

Highlights of our research involve:
1. Discovery of a new signaling molecule (CPI-17) that governs the force development of smooth muscles.
2. Characterization of the molecular basis of the signaling that regulates myosin light chain phosphatase.
3. Discovery and characterization of a new protein family of protein phosphatase regulator.


RESEARCH KEYWORDS:
Cell motility; Smooth muscle contraction; Proliferation; Hypertension; Dyspepsia; Incontinence; Cancer; Signal Transduction; G-protein; Myosin; Actin; Cytoskeleton; Protein Kinase C; Rho-kinase; Myosin Phosphatase; Protein Phosphatase; CPI-17; PHI-1; Filamin; Phosphorylation; Protein Interaction; Gene Regulation; Fluorescence
Microscopy; Biosensor; Protein Chemistry; NMR spectroscopy; Computer modeling; Proteome


CURRENT LAB MEMBER
> Noopur Advant, MS student

PREVIOUS MEMBERS
> Jason A. Kirkbride, Senior Research Associate
> Garbo D. Young, Lab Specialist/MS student
> Jee In Kim, Postdoc Fellow
> Archana Verma, Postdoc Fellow
> Yongtong Zhao, Senior Research Associate
> Shawna Dougherty, MS student
> Megumi Tsuda, Summer Intern
> Mark Urban, Lab Specialist
> Mukta Khasnis, Lab Specialist/MS student
> Kristyn Gumpper, Lab Specialist/MS Student
> Rishika Chugh, Summer Intern
> Nana Karikari, MS Student
Keywords
Cell motility; Smooth muscle contraction; Artery; Airway; GI; Bladder; Hypertension; Dyspepsia; Incontinence; Cancer; Signal Transduction; G-protein; Myosin; Actin; Phosphorylation; Cytoskeleton; Protein Kinase C; Rho-kinase; Myosin Phosphatase; Protein Phosphatase; CPI-17; PHI-1; Filamin; Biochemistry; Molecular Physiology: Molecular Biology; Cell Biology; Fluorescence microscopy; Biosensor; Structural biology; NMR spectroscopy; Computer modeling; Proteome
Publications
  • VISIT:
  • - Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/?term=masumi+eto
  • - Google Scholar: http://scholar.google.com/citations?hl=en&user=VzfkNrwAAAAJ
  • ----------------------------------------------
  • SOME ARTICLES CAN BE DOWNLOADED AT:
  • - Research Gate: https://www.researchgate.net/profile/Masumi_Eto/
  • - Jefferson Digital Common: http://jdc.jefferson.edu/physfp/
  • ----------------------------------------------
  • SELECTED PUBLICATIONS (2009 - present)
  • 45. Freitas, M. R., Eto, M., Kirkbride, J. A., Schott, C., Sassard, J., and Stoclet, J. C. (2009) Y27632, a Rho-activated kinase inhibitor, normalizes dysfunction in alpha1-adrenergic receptor-induced contraction of Lyon hypertension rat artery smooth muscle. Fund. Clin. Pharm. 23, 169-178, PMID 19298234.
  • 46. Neppl, R. L., Lubomirov, L. T., Momotani, K., Pfitzer, G., Eto, M., and Somlyo, A. V. (2009) Thromboxan A2 induced bi-directional regulation of serebral arterial tone. J. Biol. Chem., 284, 6348-6360, PMID 19095646.
  • 47. Kim, J. I., Young, G. D., Jin, L., Somlyo, A. V., and Eto, M. (2009) Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation. Histochem. Cell Biol. 132, 191-198.
  • 48. Kitazawa, T., Semba, S., Huh, Y. H., Kitazawa, K., and Eto, M. (2009) Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1. J. Physiol. 587, 3587-3603. Highlighted in "perspectives" of the Journal
  • 49. Choudhury, N., Stevenson, A. S., Somlyo, A. V., and Eto, M. (2009) Phosphorylation-dependent autoinhibition of myosin phosphatase controls Ca2+-sensitivity of smooth muscle contraction. J. Biol. Chem., 284, 21569-21579.
  • 50. Xiao, L., Eto, M., and Kazanietz, M. G. (2009) ROCK mediates phorbol ester-induced apoptosis in prostate cancer cells via p21CIP up-regulation and JNK. J. Biol. Chem., 284, 21569-21579
  • 51. Mori, S., Iwaoka, R., Eto, M., and Ohki, S. (2009) Solution structure of the inhibitory phosphorylation domain of myosin phosphatase targeting subunit 1. Proteins, 77, 732-735
  • 52. Eto, M., (2009) Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C kinase-activated PP1 inhibitors. J. Biol. Chem. 284, 35273-35277 (Minireview)
  • 53. Kim, J.I., Jung, S.W., Yang, E., Park, K.M., Eto, M., and Kim*, I.K. (2010) Heat shock augments angiotensin II induced vascular contraction through increased production of reactive oxygen species. Biochem. Biophys. Res. Comm. 399, 452-457
  • 54. Grindrod, S., Suy, S., Fallen, S., Eto, M., Toretsky, J., and Brown*, M. L., (2011) Effects of a fluorescent myosin light chain phosphatase inhibitor on prostate cancer cells. Frontiers in Cancer Molecular Targets and Therapeutics, 1:27.
  • 55. Terai, M., Eto, M., Young, G. D., Berd, D., Mastrangelo, M. J., Tamura, Y., Harigaya, K., and Sato*, T., (2012) Interleukin 6 mediates production of interleukin 10 in metastatic melanoma. Cancer Immunology and Immunotherapy, 61 (2) 145-155.
  • 56. Kim, JI., Urban, M., Young, G. D., and Eto*, M. Reciprocal regulation controlling the expression of CPI-17, a specific inhibitor protein for the myosin phosphatase in vascular smooth muscle cells. (2012) Am J Physiol- Cell Physiol. 303, C58-68
  • 57. Khromov, AS., Momotani, K., Jin, L., Artamonov, MV., Shannon, J., Eto, M., and Somlyo*, AV., Molecular mechanism of telokin mediated disinhibition of myosin light chain phosphatase and cAMP/cGMP-induced relaxation of gastrointestinal smooth muscle (2012) J Biol Chem, 287, 20975-20985
  • 58. Eto, M. and Brautigan, D.L., (2012) Endogenous inhibitor proteins that connect Ser/Thr kinases and phosphatases in cell signaling IUBMB Life (Invited Critical Review), 64, 732-739. The figure of this article was selected for the Journal cover.
  • 59. Tazzeo, T., Bates, G., Roman, HN., Lauzon, AM., Khasnis, MD., Eto, M., and Janssen, LJ. (2012) Caffeine relaxes smooth muscle through actin depolymerization Am J Physiol-Lung, 303, L334-L342. Selected in Editors Choice of the Journal.
  • 60. Eto, M., Kirkbride, J.A., Chugh, R., Karikari, N.K., and Kim, J.I. (2013) Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells. Biochem Biophys Res Comm, 434, 137-142
  • -------------------------------
  • OTHER BREAKTHROUGH PUBLICATIONS (before 2007)
  • Eto, M., Ohmori, T., Suzuki, M., Furuya, K. and Morita*, F. (1995) A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J. Biochem. 118: 1104 1107.
  • Eto, M., Senba, S., Morita, F. and Yazawa*, M. (1997) Molecular cloning of a novel Phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle. FEBS Lett. 410: 356-360. Discovery of CPI 17
  • Kitazawa*, T., Takizawa, N., Ikebe, M. and Eto, M. (1999) Reconstitution of protein kinase C-induced contractile Ca2+ sensitization in Triton X-100-demembraned rabbit arterial smooth muscle. J. Physiol.(London) 520: 139-152. Highlighted in "Perspectives" of the Journal.
  • Eto, M., Karginov, A. and Brautigan*, D. L. (1999) A novel phosphoprotein inhibitor of protein type-1 phosphatase holoenzyme. Biochemistry 38: 16952-16957 Discovery of PHI-1
  • Kitazawa*, T., Eto, M., Woodsome, T. P. and Brautigan, D. L. (2000) Agonists trigger G protein-mediated activation of CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J. Biol. Chem. 275: 9897-9900.
  • Eto, M., Wong, L., Yazawa, M. and Brautigan, D. L. (2000) Inhibition of myosin/moesin phosphatase by expression of the phosphoinhibitor protein CPI-17 alters microfilament organization and retards cell spreading. Cell Motil.Cytoskel. 46: 222-234. Contributed image for journal cover.
  • Ohki, S., Eto, M., Kariya, E., Hayano, T., Hayashi, Y., Yazawa, M., Brautigan, D. L. and Kainosho, M. (2001) Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation. J. Mol. Biol. 314: 839-849.
  • Eto, M., Bock, R., Brautigan, D. L. and Linden*, D. J. (2002) Cerebellar long-term synaptic depression requires protein-kinase-C mediated inhibition of CPI-17, a myosin/moesin phosphatase inhibitor. Neuron, 36, 1145-1158.
  • Eto, M., Kitazawa, T., and Brautigan, D. L. (2004) Phosphoprotein inhibitor CPI-17 specificity depends on allosteric regulation of the protein phosphatase-1 catalytic subunit by regulatory subunits. Proc. Natl. Acad. Sci. USA. 101, 8888-8893. (Track II, direct submission)
  • Dimopoulous, G. J., Semba, S., Kitazawa, K., Eto, M., and Kitazawa, T., (2007) Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. Circ. Res., 100, 121-129. Highlighted in "Editorials" of the Journal.
  • Eto, M., Kirkbride, J., Elliott, E., Lo, S. H., and Brautigan, D. L., (2007) Association of the tensin N-terminal PTP domain with alpha isoform of protein phosphatase-1 in focal adhesions. J. Biol. Chem, 282, 17806-17815.
  • Eto, M., Kitazawa, T., Matsuzawa, F., Aikawa, S., Kirkbride, J. A., Isozumi, N., Nishikawa, Y., Brautigan, D. L., and Ohki, S. (2007) Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor. Structure,15, 1591-1602.
  • ----------------------------------
  • REVIEW ARTICLES:
  • 1. Ohki, S., Eto, M., Matsuzawa, F., and Kainosho, M. (2005) Structural basis of a myosin phosphatase inhibitory protein, CPI-17. Seibutsu Butsuri, 45 (2) 72-77
  • 2. Eto, M., and Yazawa, M. (2005) Function and regulation of Ser/Thr-specific protein phosphatase-1 (PP1). Seikagaku, 77 (10), 1308-1316
  • 3. Eto, M. (2008) Mechanism underlying myosin phosphatase regulation. Vascular Biology and Medicine, 9 (3), 213 221
  • 4. Eto, M., (2009) Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C kinase-activated PP1 inhibitors. J. Biol. Chem. 284, 35273-35277 (Minireview)
  • 5. Eto, M. and Brautigan, D.L., (2012) Endogenous inhibitor proteins that connect Ser/Thr kinases and phosphatases in cell signaling IUBMB Life (Invited Critical Review), 64, 732-739. The figure of this article was selected for the Journal cover.

Individual Expertise profile of Masumi Eto, Ph.D., Copyright © Masumi Eto, Ph.D..
Last Updated by Masumi Eto, Ph.D. : Thursday, May 2, 2013 2:03:58 PM



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