Education, Honors, Awards

  • Henry Dreyfus Teacher-Scholar Award (2018)
  • Associate Professor James Madison University (2017 - present)
  • Assistant Professor James Madison University (2011 - 2017)
  • Postdoctoral Fellow, Johns Hopkins University (2009-2011)
  • Adjunct Instructor, Loyola University (MD) (2010)
  • Postdoctoral Fellow, University of Maryland Baltimore (2008)
  • Ph.D., Biochemistry, University of Maryland Baltimore (2003-2008)
  • M.S., Cellular and Molecular Biology, University of Pennsylvania (2000-2002)
  • B.S., Biology, Haverford College (1996-2000)

Research Interests

  • Protein structure/function relationships
  • NMR and X-ray protein structure determination
  • Protein dynamics
  • Small molecule and peptide agonist/antagonists of proteins

Research Description

Think about how versatile a human muscle cell must be- it has to have the structural integrity to withstand strong forces, yet must be pliable enough to bend and stretch repeatedly without breaking.  Muscles accomplish this contrasting need for strength and motion through a complex lattice of proteins and membranes.  Obscurin, a large protein discovered within the past decade, helps in this feat by linking the muscle contractile apparatus with various cell membranes. This large, highly modular protein is made up of at least 71 discrete domains.  Most of these domains act as either adhesion points for other structural molecules, signaling moieties, or linker regions. Additionally, the protein contains elements that sense stretch, and can promote muscle repair.  Likewise, mutations in these domains are linked to muscle diseases such as cardiomyopathy and several muscular dystrophies.  My lab is focused on studying the structure of the individual domains of obscurin and obscurin-binding partners.  This will help determine the cellular and molecular mechanism of how obscurin performs its job with atomic-scale resolution.  To do this, students in Dr. Wright’s lab with use a variety of structural biochemistry techniques including protein x-ray crystallography and multidimensional heteronuclear NMR analysis.  Insight gained from these studies will allow both better understanding of the molecular basis of human muscle diseases, and potentially novel ways to treat these diseases.

Selected Recent Publications (JMU undergraduates are underlined)

  • Ackermann MA, King B, Perry NA, Bobbili PJ, Rudloff M, Berndsen CE, Wright NT, Hecker PA, Kontrogianni-Konstantopoulos A, Small Obscurins at the Intercalted Disc Mediate Cardiomyocyte Adhesion and Size via the PI3K/AKT/mTOR Pathway J. Cell. Cardiol. 2017 Oct; 111: 27-39
  • Rossi D, Palmio J, Galli L, Barone V, Caldwell TAPolicke RA, Berndsen CE, Wright NT, Romero N, Malfatti E, Brochier G, Stojkovic, Jordanova A, Guergueltcheva A, Hackman P, Romero NB, Eymard B, Udd B, Sorrentino V, Digenic Inheretence of a FLNC frameshift and an OBSCN Variant in a Family with Distal Muscular Dystrophy, PLoS One, 2017 Oct; 12(10) e0186642
  • Hu LR, Ackermann MA, Hecker PA, Prosser BL, King B, O’Connell KA, Asico LD, Jose PA, Meyer LC, Berndsen CE, Wright NT, Lederer WJ, Kontrogianni-Konstantopoulos A, Arrhythmia and deregulated Ca2+cycling underlie the development of hypertrophic cardiomyopathy due to mutant obscurins, Science Advances  2017 Jun 7; 3(6)
  • Santiago AE, Yan MB, Tran MB, Wright NT, Luzader DH, Kendall MM, Ruiz-Perez F, Nataro JP, A large family of anti-activator accompanying XylS/AraC family regulatory proteins, Molecular Microbiology (accepted May 2016)
  • Temple JE, Oehler MC, Wright NT, Chemical shift assignments of the 2domain of human obscurin A, J. Biomolecular NMR Assignments, 2016 Apr; 10(1), 63-5
  • Wright NT, Heteronuclear Multidimensional NMR in a Teaching Laboratory, J. Chem. Educ., 2016; 93(2), 287-91
  • Caldwell CA, Sumner I, Wright NT, Mechanical dissociation of the M-band titin/obscurin complex is directionally dependent, FEBS Letters, 2015 Jul 8; 589(15), 1735-9
  • Putney DR, Todd EA, Berndsen CE, Wright NT, Chemical Shift assignments of Ubc13 from s cerivesia. J. Biomolecular NMR Assignments, 2015 Oct; 9(2), 407-10
  • Rudloff MW, Woosley AN, Wright NT, Biophysical Characterization of naturally occurring titin M10 mutations, Prot. Sci. ,2015 Jun; 24(6): 946-55
  • Meyer LC, Wright NT, Structure of giant muscle proteins, Front. Physiol. 2013 Dec 12; 4:368
  • Liriano MA, Varney KM, Wright NT, Hoffman CL, Toth EA, Ishima R, Weber DJ, Target Binding to S100B Reduces Dynamic Properties and Increases Ca2_-binding Affinity for Wild Type and EF-Hand Mutant Proteins, J Mol Biol 2012 Oct 26; 423(3): 365-85
  • Buller AR, Labonte JW, Freeman MF, Wright NT, Schildbach JF, Townsend CA, Autoproteolytic Activation of ThnT Results in Structural Reorganization Necessary for Substrate Binding and Catalysis, Journal of Molecular Biology 2012 Sep 28;422(4):508-18
  • Wright NT, Hemmis CW, Raththagala M, Edwards S, Curtis JE, Krueger S, Schildbach JF, Solution structure and small angle scattering analysis of TraI (381-569), Proteins, Aug 2012; 80(9) 2250-61
  • Buller AR, Freeman MF, Wright NT, Schildbach JF, Townsend CA, Insights into cis-autoproteolysis reveal a reactive state formed through conformational rearrangement, PNAS 2012 Feb 14; 109(7):2308-13
  • Hernández-Ochoa EO, Prosser BL, Wright NT, Contreras M, Weber DJ, Schneider MF, Augmentation of Cav1 channel current and action potential duration after uptake of S100A1 in sympathetic ganglion neurons, Am J Physiol Cell Physiol 2009 Oct; 97(4):C955-70
  • Wright NT, Cannon BR, Zimmer DB, Weber DJ, Structure and Function of S100A1 (review).  Current Chemical Biology 2009 May; 3(2): 138-145
  • Wright NT, Cannon BR, Morgan MT, Varney KM, Zimmer DB, Weber DJ, Solution structure of S100A1 bound to the CapZ peptide (TRTK12), Journal of Molecular Biology 2009 Mar 13; 386(5): 1265-77
  • Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ, Ca2+-S100A1 and Ca2+-calmodulin compete for the same binding site on the ryanodine receptor, Journal of Biological Chemistry, 2008 Sep 26; 283(39):26676-83
  • Prosser BL*, Wright NT*, Hernãndez-Ochoa EO, Varney KM, Liu Y, Olojo RO, Zimmer DB, Weber DJ, Schneider MF.S100A1 binds to the calmodulin binding site of ryanodine receptor and modulates skeletal muscle EC coupling, Journal of Biological Chemistry, 2007 Feb 22; 283(8):5046-57
  • Wright NT, Varney KM, Ellis KC, Markowitz J, Gitti RK, Zimmer DB, Weber DJ, The three-dimensional solution structure of Ca2+-bound S100A1 as determined by NMR spectroscopy, Journal of Molecular Biology 2005 Oct 21; 353(2):410-26

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