Doju Yoshikami
Professor of School of Biological Sciences
Molecular Neuroscience
Cellular Neuroscience
e-mail: yoshikami@bioscience.utah.edu
B.A. 1965, Reed College; Ph.D. 1970, Cornell University; NIH Postdoctoral Fellow 1970-1971,
Cornell University; NSF Postdoctoral Fellow, 1971-1973, Harvard Medical School
RESEARCH:
Cellular and molecular physiology of ion channels
Dr. Yoshikami's work is focused on the cellular and molecular physiology of voltage-gated and ligand-gated ion channels. In collaboration with Professors B.M. Olivera and J.M. McIntosh, he is identifying and characterizing the ion-channel targets and modes of action of a variety of neuroactive peptides (the conotoxins). In particular, he is studying the five families of conotoxins that target voltage-gated sodium channels (VGSCs), including members of the μ-conotoxin family and the recently discovered μO§-conotoxin GVIIJ. The detailed pharmacology of these conotoxins is being studied using endogenous VGSCs in dissociated neurons and cloned ion channels exogenously expressed in Xenopus oocytes or mammalian cell lines. He is also using the conotoxins to probe the functional roles of given isoforms of VGSCs in intact, isolated tissue preparations.
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., and 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. http://doi.org/10.1074/jbc.M115.697672
Zhang, M.-M., Gajewiak, J., Azam, L., Bulaj, G., Olivera, B.M., and Yoshikami, D. (2015) Probing the Redox States of Sodium Channel Cysteines at the Binding Site of μO§-Conotoxin GVIIJ. Biochemistry, 54(25):3911–3920. http://doi.org/10.1021/acs.biochem.5b00390
Wilson, M.J., Zhang, M.-M., Gajewiak, J., Azam, L., Rivier, J.E., Olivera, B.M., and 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. http://doi.org/10.1152/jn.01004.2014
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. http://doi.org/10.1073/pnas.1324189111
Zhang, M.-M., Wilson, M.J., Gajewiak, J., Rivier, J.E., Bulaj, G., Olivera, B.M., and 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. http://doi.org/10.1111/bph.12119
Zhang, M.-M., Wilson, M.J., Azam, L., Gajewiak, J., Rivier, J.E., Bulaj, G., Olivera, B.M., and 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. http://doi.org/10.1111/bph.12051
Teichert, R.W., Smith, N.J., Raghuraman, S., Yoshikami, D., Light, A.R., and Olivera, B.M. (2012) Functional profiling of neurons through cellular neuropharmacology. Proc Nat'l Acad Sci, 109(5):1388–1395. http://doi.org/10.1073/pnas.1118833109
Wilson, M.J., Zhang, M.-M., Azam, L., Olivera, B.M., Bulaj, G., and 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. http://doi.org/10.1124/jpet.110.178343
Wilson, M.J., Yoshikami, D., Azam, L., Gajewiak, J., Olivera, B.M., Bulaj, G., and Zhang, M.-M. (2011) μ-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. http://doi.org/10.1073/pnas.1107027108
Zhang, M.-M., Gruszczynski, P., Walewska, A., Bulaj, G., Olivera, B. M., and Yoshikami, D. (2010) Cooccupancy of the outer vestibule of voltage-gated sodium channels by μ-conotoxin KIIIA and saxitoxin or tetrodotoxin. J Neurophysiol, 104(1):88–97. http://doi.org/10.1152/jn.00145.2010