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email: yoshikami@bioscience.utah.edu |
Professor of Biology The Yoshikami Lab home page Molecular Neuroscience Cellular Neuroscience |
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 of a variety of neuroactive peptides (the conotoxins). These peptides can block specific subtypes of ligand-gated channels (e.g., acetylcholine or glutamate receptors) while others target specific isoforms of voltage-gated sodium, calcium or potassium channels. The detailed pharmacology of the conotoxins is being studied in dissociated neurons and in Xenopus oocytes expressing cloned ion channels. He is also using the conotoxins to probe the functional roles of given isoforms of ion channels in intact, isolated tissue preparations. For example, he is examining the involvement of tetrodotoxin-resistant sodium channels in nociception with recently discovered conotoxins that blocks these channels (see Bulaj et al., 2005 and Zhang et al., 2006).
Selected Publications
Bulaj, G., Zhang, M.M., Green, B.R., Fiedler, B., Layer, R.T., Wei, S., Nielsen, J.S., Low, S.J., Klein, B.D., Wagstaff, J.D., Chicoine, L., Harty, T.P., Terlau, H., Yoshikami, D., and Olivera, B.M. (2006) Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity. Biochemistry, 45:7404-7414.
Zhang, M.M., Fiedler, B., Green, B.R., Catlin, P., Watkins, M., Garrett, J.E., Smith, B.J., Yoshikami, D., Olivera, B.M., and Bulaj, G. (2006) Structural and functional diversities among mu-conotoxins targeting TTX-resistant sodium channels. Biochemistry, 45:3723-3732.
Buczek, O., Yoshikami, D., Bulaj, G., Jimenez, E.C., and Olivera, B.M. (2005) Post-translational amino acid isomerization: a functionally important D-amino acid in an excitatory peptide. The Journal of Biological Chemistry, 280:4247-4253.
West, P.J., Bulaj, G., and Yoshikami, D. (2005) Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian sympathetic nervous system. Journal of Neurophysiology, 94:3916-3924.
Dowell, C., Olivera, B.M., Garrett, J.E., Staheli, S.T., Watkins, M., Kuryatov, A., Yoshikami, D., Lindstrom, J.M., and McIntosh, J.M. (2003) a-conotoxin PIA is selective for a6 subunit-containing nicotinic acetylcholine receptors. J. Neurosci., 23:8445-8452.
Keizer, D.W., West, P.J., Lee, E.F., Yoshikami, D., Olivera, B.M., Bulaj, G., and Norton, R.S. (2003) Structural basis for tetrodotoxin-resistant sodium channel binding by m-conotoxin SmIIIA. J. Biol. Chem. 278:46805-46813.
Jimenez, E.C., Shetty, R.P. Lirazan, M., Rivier, J., Walker, C., Abogadie, F.C., Yoshikami, D., Cruz, L.J., and Olivera, B. M. (2003) Novel excitatory Conus peptides define a new conotoxin superfamily. J. Neurochem., 85:610-621.
West, P.J., Bulaj, G., Garrett, J.E., Olivera, B.M., and Yoshikami, D. (2002) m-conotoxin SmIIIA, a potent inhibitor of tetrodotoxin-resistant sodium channels in amphibian sympathetic and sensory neurons. Biochemistry, 41:15388-15393.
McIntosh, J.M., Dowell, C., Watkins, M., Garrett, J.E., Yoshikami, D., and Olivera, B.M. (2002) a-Conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors. J. Biol. Chem., 277:33610-33615.
Bulaj, G., DeLaCruz, R., Azimi-Zonooz, A., West, P., Watkins, M., Yoshikami, D., and Olivera, B. M. (2001) g-Conotoxin structure/function through a cladistic analysis. Biochemistry 40:13201-13208.
Kulak, J.M., McIntosh, J.M., Yoshikami, D., and Olivera, B.M. (2001) Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels. J. Neurochem., 77:1581-1589.
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