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Doju Yoshikami Back to Faculty

Doju Yoshikami

Professor Emeritus

Ph.D. Cornell University

Office/Building: Biol 217A
Phone: 801-581-3084
Email: yoshikami@bioscience.utah.edu

Research Statement

Ion channels perform critical roles in intra- and intercellular communication in nerve and muscle. Their importance can be readily appreciated by considering the multitude of neurotoxins that target them. Our laboratory collaborates closely with the Olivera and McIntosh laboratories and studies ion channels by exploiting toxins from a bountiful source, namely venomous snails in the genus Conus. Of particular interest are �- and μO�-conotoxins, which are small disulfide-bridged peptides that block voltage-gated sodium channels (VGSCs). Mammals have several genes encoding VGSCs, and one goal of our research is to identify conotoxins, or engineered derivatives thereof, that discriminate among the different isoforms of VGSCs. We use electrophysiological methods to examine VGSCs exogenously expressed in Xenopus oocytes as well as those expressed by autonomic, sensory and motor neurons and skeletal muscle in different species of animals.

Specific Interests
  • Ligand- and voltage-gated ion channels
  • Neurotoxins that target ion channels, including those involved in nociception

Selected Publications

  • Green, B.R., Gajewiak, J., Chhabra, S., Skalicky, J. J., Zhang, M.-M., Rivier, J. E., Bulaj, G., Olivera, B. M., Yoshikami, D., & Norton, R. S. (2016). Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO�-GVIIJ. J Biol Chem, 291(13), 7205�7220.
  • Zhang, M.-M., Gajewiak, J., Azam, L., Bulaj, G., Olivera, B. M., & Yoshikami, D. (2015). Probing the Redox States of Sodium Channel Cysteines at the Binding Site of μO�-Conotoxin GVIIJ. Biochemistry, 54(25), 3911�3920.
  • Wilson, M. J., Zhang, M.-M., Gajewiak, J., Azam, L., Rivier, J. E., Olivera, B. M., & Yoshikami, D. (2015). α- And β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO�-conotoxin GVIIJ. J Neurophysiol, 113(7), 2289�2301.
  • Gajewiak, J, et al. (2014). A disulfide tether stabilizes the block of sodium channels by the conotoxin μO�-GVIIJ. Proc Nat�l Acad Sci, 111(7), 2758�2763.
  • Zhang, M.-M., Wilson, M. J., Gajewiak, J., Rivier, J. E., Bulaj, G., Olivera, B. M., & Yoshikami, D. (2013). Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins. Brit J Pharmacol, 169(1), 102�114.
  • Zhang, M.-M., Wilson, M. J., Azam, L., Gajewiak, J., Rivier, J. E., Bulaj, G., Olivera, B. M., & Yoshikami, D. (2013). Co-expression of NaV β subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking μ-conotoxins. Br J Pharmacol, 168(7), 1597�1610.
  • Teichert, R. W., Smith, N. J., Raghuraman, S., Yoshikami, D., Light, A. R., & Olivera, B. M. (2012). Functional profiling of neurons through cellular neuropharmacology. Proc Nat�l Acad Sci, 109(5), 1388�1395.
  • Wilson, M. J., Zhang, M.-M., Azam, L., Olivera, B. M., Bulaj, G., & Yoshikami, D. (2011). Navβ subunits modulate the inhibition of Nav1.8 by the analgesic gating modifier μO-conotoxin MrVIB. J Pharmacol Exp Therap, 338(2), 687�693.
  • Wilson, M. J., Yoshikami, D., Azam, L., Gajewiak, J., Olivera, B. M., Bulaj, G., & Zhang, M.-M. (2011). {micro}-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Nat�l Acad Sci, 108(25), 10302�10307.
  • Zhang, M.-M., Gruszczynski, P., Walewska, A., Bulaj, G., Olivera, B. M., & Yoshikami, D. (2010). Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxin. J Neurophysiol, 104(1), 88�97. http://doi.org/10.1152/jn.00145.2010