BALDOMERO M OLIVERA portrait
  • Distinguished Professor, Biology
  • HCI Experimental Therapeutics Group Member , Huntsman Cancer Institute

Research Summary

Our research has focused on venomous marine snails, in particular, those that belong to the genus Conus ("cone snails"). Cone snails are highly specialized venomous predators. The major research project in our laboratory is the discovery and characterization of their venom components, identification of their molecular targets, and an exploration of potential biomedical applications.

Education

  • B.S., Chemistry, Univ. of the Philippines, Quezon City, PI
  • Ph.D., Biophysical Chemistry, California Inst. of Technology, Pasadena, CA
  • Post-doc, Biochemistry, Stanford University, Palo Alto, CA

Biography

Baldomero (“Toto”) Olivera grew up in the Philippines; he received his B.S. degree in Chemistry from the University of the Philippines, his Ph.D. working on the Biophysical Chemistry of DNA at Caltech, followed by postdoctoral work in Biochemistry at Stanford. His early research contributions include the discovery and biochemical characterization of E. coli DNA ligase, a key enzyme of DNA replication and repair that is widely used in recombinant DNA technology. He is presently a Distinguished Professor of Biology at the University of Utah.

 

Toto Olivera initiated the characterization of the venoms of the predatory cone snails.  A large number of peptide neurotoxins ("conopeptides") are present in these venoms, and their characterization led Olivera’s research group to a broad involvement with molecular neuroscience.  Conus venom components are used to investigate the function of individual ion channels and receptors.  The cone snail project has raised wide-ranging biological questions, from mechanisms of protein folding and post-translational modification, to gene organization and mechanisms of speciation.  Several peptides discovered in Olivera’s laboratory reached human clinical trials and one (Prialt) has been approved for the treatment of intractable pain. He is a member of the American Philosophical Society, the U.S. National Academy of Science, and the Institute of Medicine.  He was given the Outstanding Alumni Award of Caltech, the Redi Award from the International Society for Toxinology and the Harvard Foundation Scientist of the Year 2007 Award. As an HHMI professor, Dr. Olivera has implemented an outreach program to instill an interest in science in young students by educating them about scientific principles they can observe in the organisms that they see every day.

HCI Experimental Therapeutics

 

HCI Experimental Therapeutics Group-Member

Olivera lab, recent publications

            The enclosed list of publications (last 5 years) are selected for being particularly relevant to the HCI mission. Olivera’s lab works on finding non-opioid molecular targets for severe pain, particularly intractable pain that is no longer relieved by morphine or other opioids. The 16 publications are relevant to this work (total number of publications of the lab in the last 5 years, 55). A particularly important direction is work done by our collaborative group on a peptide that appears to prevent neuropathic pain resulting from chemotherapy; potentially, this could not only alleviate neuropathy as a side effect, but could allow a change in the dose and duration of the chemotherapy to make it significantly more effective. The manuscripts that are directly relevant to these developments are marked with an asterisk.

Olivera, B.M., Showers Corneli, P., Watkins, M., and Fedosov, A. (2014). Biodiversity of Cone Snails and other Venomous Marine Gastropods: Evolutionary Success Through Neuropharmacology., Annual Review of Animal Biosciences 2:487 -513.

Raghuraman, S., Garcia, A., III, Anderson, T., Twede, V., Curtice, K.J., Ramirez, J.-M., Olivera, B.M., and Teichert, R.W. (2014) Defining modulatory inputs into CNS neuronal subclasses through functional pharmacological profiling, PNAS 111(17):6449-54.

Teichert RW, Memon T, Aman JW, Olivera BM. (2014) Using Constellation Pharmacology to define comprehensively a somatosensory neuronal subclass. PNAS USA, 111(6):2319-24.

Christensen SB, Bandyopadhyay PK, Olivera BM, McIntosh JM. (2015) αS-conotoxin GVIIIB potently and selectively blocks α9α10 nicotinic acetylcholine receptors. Biochem Pharmacol. 96(4):349-56.

Lee, H. K., L. Zhang, M. D. Smith, A. Walewska, N. A. Vellore, R. Baron, J. M. McIntosh, H. S. White, B. M. Olivera, and G. Bulaj. (2015) A marine analgesic peptide, Contulakin-G, and neurotensin are distinct agonists for neurotensin receptors: uncovering structural determinants of desensitization properties. Front Pharmacol 6:11.

Teichert, R. W.; Olivera, B. M.; McIntosh, J. M.; Bulaj, G.; Horvath, M. P. (2015) The Molecular Diversity of Conoidean Venom Peptides and their Targets: From Basic Research to Therapeutic Applications In Venom to Drugs: Venom as a Source for the Development of Human Therapeutics. King, G. F., Ed. RSC Publishing: London, Vol. RSC Drug Discovery, pp 163-203.

Teichert, R. W.; Schmidt, E. W.; Olivera, B. M., (2015) Constellation Pharmacology: A new paradigm for drug discovery. Ann. Rev. Pharmacology and Toxicology, (55)573-589.

Wilson, M. J., M. M. Zhang, J. Gajewiak, L. Azam, J. E. Rivier, B. M. Olivera, and D. Yoshikami. (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.

 Zhang MM, Gajewiak J, Azam L, Bulaj G, Olivera BM, Yoshikami D. (2015) Probing the Redox States of Sodium Channel Cysteines at the Binding Site of μO§-Conotoxin GVIIJ. Biochemistry. 54(25):3911-20.

Green BR, Gajewiak J, Chhabra S, Skalicky JJ, Zhang MM, Rivier JE, Bulaj G, Olivera BM, Yoshikami D, Norton RS. (2016) Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO§-GVIIJ. J Biol Chem. 291(13):7205-20.

Green BR & Olivera BM. (2016) Venom Peptides from Cone Snails: Pharmacological Probes for Voltage-gated Sodium Channels. In R. French, S. Noskov CTM 78 Na Channels Across Phyla and Function. Chennai, India: Elsevier. 78:65-86.

Memon T, Chase K, Leavitt LS, Olivera BM, Teichert RW. (2017) TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons. Neuroscience. 353:76-86.

Olivera, B.M., H. Safavi-Hemami, Raghuraman S., Teichert R.W. (2017) Cone Snail Venom Peptides and Future Biomedical Applications of Natural Products In Chemical Biology of Natural Products. Editors: Newman, Cragg.

**Romero HK, Christensen SB, Di Cesare Mannelli L, Gajewiak J, Ramachandra R, Elmslie KS, Vetter DE, Ghelardini C, Iadonato SP, Mercado JL, Olivera BM, McIntosh JM. (2017) Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Proc Natl Acad Sci U S A. 114(10)E1825-E1832.
Giacobassi MJ, Leavitt LS, Raghuraman, S, Alluri R, Chase K, finol-Urdaneta RK, Terlau H, Teichert RW, Olivera BM. (2019) An integrative approach to the facile functional classification of DRG neuronal subclasses Proc Natl Acad Sci U S A. (in press).
Memon T, Yarishkin O, Reilly CA, Kri┼żaj D, Olivera BM, Teichert RW.  (2019) trans-Anethole of Fennel Oil is a Selective and Nonelectrophilic Agonist of the TRPA1 Ion Channel. Mol Pharmacol. 95(4):433-441.
**Safavi-Hemami H, Brogan SE, Olivera BM. (2019) Pain therapeutics from cone snail venoms: From Ziconotide to novel non-opioid pathways. J Proteomics. 190:12-20.
van Hout M, Valdes A, Christensen SB, Tran PT, Watkins M, Gajewiak J, Jensen AA, Olivera BM, McIntosh JM. (2019) α-Conotoxin VnIB from Conus ventricosus is a potent and selective antagonist of α6β4* nicotinic acetylcholine receptors. Neuropharmacology. 157:107691. doi: 10.1016/j.neuropharm.2019.107691. Epub 2019 Jun 28.