BALDOMERO M. OLIVERA
|Distinguished Professor of Biology
The Olivera Lab Home Page and Olivera Lab
Neurobiology of Disease
Ion channels, membrane receptors and sensory transduction
Dr. Olivera and colleagues are interested in the ion channels and receptors, which mediate signaling in the nervous system. They have isolated neurotoxins from the venoms of the predatory cone snails, Conus that target specific molecular isoforms of ion channels and receptors, and are characterizing the targets of some of these peptide toxins. Present work is focused on both ligand-gated and voltage-activated ion channels. Dr. Olivera's laboratory has characterized a set of unique toxins, the omega-conotoxins, which irreversibly bind (and block) these calcium channels; an ω-conotoxin discovered in the Olivera lab is now an approved drug for pain. The venom for a single Conus species contains more than 80 active peptides, which fall into over 15 classes. The long-range goal is to use these toxins as an entree for studying key molecules in the CNS. The fact that these toxins can be synthesized and radiolabeled will permit characterization of the key CNS molecules that are the targets of these peptides.
Twede, V.D., Teichert, R.W., Walker, C.S., Gruszczynski, P., Kazmierkiewicz, R., Bulaj, G., and Olivera, B.M. (2009) Conantokin-Br from Conus brettinghami and selectivity determinants for the NR2D subunit of the NMDA receptor. Biochemistry, 48(19):4063-4073.
Olivera, B. M., Quik, M., Vincler, M., and McIntosh, J.M. (2008) Subtype-selective conopeptides targeted to nicotinic receptors: Concerted discovery and biomedical applications. Channels (Austin), 2(2):143-152.
Olivera, B.M. (2006) Conus peptides: biodiversity-based discovery and exogenomics. J Biol Chem, 281:31173-31177.
Vincler, M., Wittenauer, S., Parker, R., Ellison, M., Olivera, B.M., and McIntosh, J.M. (2006) Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A, 103:17880-17884.
Terlau, H., and Olivera, B.M. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol Rev, 84:41-68.
Ferber, M., Sporning, A., Jeserich, G., DeLaCruz, R., Watkins, M., Olivera, B.M., and Terlau, H. (2003) A novel Conus peptide ligand for K+ channels. J. Biol. Chem., 278:2177-2183.
White, H.S., McCabe, R.T., Armstrong, H., Donevan, S.D., Cruz, L.J., Abogadie, F.C., Torres, J., River, J.E., Paarmann, I., Hollmann, M., and Olivera, B.M. (2000) In vitro and in vivo characterization of conantokin-R, a selective NMDA receptor antagonist isolated from the venom of the fish-hunting snail Conus radiatus. J. Pharmacol. Exp. Therapeu. 292:425-432.
England, L.J., Imperial, J., Jacobsen, R., Craig, A.G., Gulyas, J., Akhtar, M., Rivier, J., Julius, D., and Olivera, B.M. (1998) Inactivation of a serotonin-gated ion channel by a polypeptide toxin from marine snails. Science 281:575-578.
Olivera, B.M., Miljanich, G., Ramachandran, J., and Adams, M.E. (1994) Calcium channel diversity and neurotransmitter release: The omega-conotoxins and omega-agatoxins. Ann. Rev. Biochem. 63: 823-867.
Olivera, B.M., Rivier, J., Scott, J.K., Hillyard, D.R., and Cruz, L.J. (1991) Conotoxions. J. Biol. Chem. 266: 22067-22070.
Olivera, B.M., River, J., Clark, C., Ramilo, C.A., Corpuz, G.P., Abogadie, F.C., Mena, E.E., Woodward, S.R., Hillyard, D.R., and Cruz, L.J. (1990) Diversity of Conus neuropeptides. Science 249: 257-263.