Professor Richard Lewis

Professorial Research Fellow - GL

Institute for Molecular Bioscience

Affiliate Professor

School of Biomedical Sciences
Faculty of Medicine
r.lewis@uq.edu.au
+61 7 334 62984

Overview

Professor Lewis started working on toxins during his PhD studies at the University of Queensland, where he researched the nature and pharmacology of ciguatoxins responsible for ciguatera fish poisoning. After 10 years with the Queensland Department of Primary Industry following this line of research, he moved back to The University of Queensland to initiate research into the phamacology of conotoxins, small venom peptides produced by carnivorous cone snails. This research led to the isolation and characterisation of several new classes of conotoxins, including two (w-CVID and Xen2174) that were developed clinically. His current research focusses on the discovery, evolution and structure-function of venom peptides, especially those with potential for the treatment of difficult to manage pain.

Research Interests

  • Molecular Pharmacology
    Currently we are investigating conotoxins that selectively target the nicotinic acetylcholine and NMDA receptors, the voltage sensitive calcium and sodium channels, and the noradrenaline transporter. Complimentary interactions between conotoxins and their receptor are being established to better understand where and how they act at the molecular level. The aim of this research is to develop research tools and potential therapeutics for poorly treated diseases such as chronic pain. This research involves assay-guided isolation of venom peptides, peptide synthesis, tissue pharmacology, radioligand binding and electrophysiological studies, as well as receptor mutagenesis, modelling and docking. Specific projects include:
  • Discovery of novel bioactive peptides (conotoxins or conopeptides) from Cone snail venom. The nicotinic acetylcholine receptor is a nonselective cation channel stimulated by acetylcholine and selectively inhibited by �-conotoxins.
  • We have discovered several new �-conotoxins using receptors expressed in oocytes to guide crude venom fractionation. Several had unusual structure and subtype selectivity. Homology modelling and docking studies are allowing us to understand, at the molecular level, how these selectivity differences arise
  • The NMDA receptor, an important non-selective cation channel in the brain, is inhibited by conantokins. Using conantokin analogues, we recently found that specific subtypes of the NMDA receptor are lost in Alzheimer's disease. Currently we are trying to establish their identity to better understand how Alzheimer's disease develops
  • The voltage sensitive N-type calcium channel, a neuronal calcium channel found in pathways involved in the transmission of painful stimuli, is inhibited by �-conotoxins. We recently identified a novel variant of this channel using CVID. This variant is currently under investigation to understand its role in chronic pain
  • The voltage sensitive sodium channels, particularly those found in neurons inhibited by �-conotoxins, are also under investigation. We have established that �-conotoxins selectively target persistent forms of the TTX-sensitive sodium channel. The nature and role of these sodium channels is currently under investigation
  • The noradrenaline transporter (NET) is the primary route of noradrenaline removal from synapses. We have identified �-conotoxins as the first peptide inhibitor of NET, and its effectiveness in treating neuropathic pain and depression. We are presently establishing the complimentary interactions between �-conotoxins and NET to understand where and how they act at the molecular level. Our research has led to the formation of the biotechnology company Xenome Ltd. Xenome is focused on discovering and developing new pharmaceuticals from the venom of Australian animals.

Research Impacts

Professor Lewis' research on novel analgaesics from Australian venomous animals has the potential to change the way severe pain is currently treated. His research on ciguatera has the potential to improve the management of this severe illness associated with the consumption of tropical reef fish that affects ~50,000 people per annum.

Qualifications

  • PhD, The University of Queensland
  • Bachelor of Science, James Cook University

Publications

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Grants

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Supervision

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Publications

Book

  • Wong, Yiu-Chung and Lewis, Richard J. (2017). Analysis of Food Toxins and Toxicants. Oxford United Kingdom: Wiley Blackwell. doi: 10.1002/9781118992685

Book Chapter

  • Inserra, Marco, Lavrukhina, Yelena, Jones, Alun, Lewis, Richard J. and Vetter, Irina (2017). Ciguatoxin detection methods and high-throughput assays. Analysis of food toxins and toxicants. (pp. 469-487) Oxford, United Kingdom: Wiley Blackwell. doi: 10.1002/9781118992685.ch15

  • Lewis, Richard J. and Vetter, Irina (2016). Ciguatoxin and ciguatera. Marine and freshwater toxins. (pp. 71-92) edited by P. Gopalakrishnakone, Vidal Haddad Jr., Aurelia Tubaro, Euikyung Kim and William R. Kem. Dordrecht, The Netherlands: Springer. doi: 10.1007/978-94-007-6419-4_13

  • Dutertre, Sebastien, Griffin, John and Lewis, Richard J. (2016). Phyla Molluska: the venom apparatus of cone snails. Marine and freshwater toxins. (pp. 327-340) edited by P. Gopalakrishnakone, Vidal Haddad Jr., Aurelia Tubaro, Euikyung Kim and William R. Kem. Dordrecht, The Netherlands: Springer. doi: 10.1007/978-94-007-6419-4_8

  • Lewis, Richard J. (2015). Case Study 1: Development of the Analgesic Drugs Prialt (R) and Xen2174 from Cone Snail Venoms. Venoms to drugs: venom as a source for the development of human therapeutics. (pp. 245-254) edited by Glenn F. King. Cambridge, United States: RSC. doi: 10.1039/9781849737876-00245

  • Lewis, Richard J., Vetter, Irina, Cardoso, Fernanda C., Inserra, Marco and King, Glenn (2015). Does nature do ion channel drug discovery better than us?. Ion channel drug discovery. (pp. 297-313) edited by Brian Cox and Martin Gosling. Cambridge, United Kingdom: Royal Society of Chemistry. doi: 10.1039/9781849735087-00297

  • Dutertre, Sebastien, Undheim, Eivind, Pineda, Sandy S., Jin, Ai-Hua (Jean), Lavergne, Vincent, Fry, Bryan G., Lewis, Richard J., Alewood, Paul F. and King, Glenn F. (2015). Venoms-Based Drug Discovery: Proteomic and Transcriptomic Approaches. Venoms to Drugs. (pp. 80-96) edited by King, Glenn F. London, United Kingdom: Royal Society of Chemistry. doi: 10.1039/9781849737876-00080

  • Vetter, Irina, Zimmermann, Katharina and Lewis, Richard J. (2014). Ciguatera toxins: pharmacology, toxicology and detection. Seafood and freshwater toxins: pharmacology, physiology, and detection. (pp. 925-950) edited by Luis M. Botana. Boca Raton, FL, United States: CRC Press.

  • Amade, Philippe, Mehiri, Mohamed and Lewis, Richard J. (2014). Outstanding marine biotoxins: STX, TTX, and CTX. Outstanding marine molecules: chemistry, biology, analysis. (pp. 23-44) edited by Stéphane La Barre and Jean-Michel Kornprobst. Weinheim, Germany: Wiley Blackwell. doi: 10.1002/9783527681501.ch02

  • Lavergne, Vincent, King, Glenn F., Lewis, Richard J. and Alewood, Paul F. (2014). Peptide therapeutics from venomous creatures. Pain therapeutics: current and future treatment paradigms. (pp. 217-246) edited by Charlotte Allerton. London, United Kingdom: Royal Society of Chemistry. doi: 10.1039/9781849737715-00217

  • Vetter, I. and Lewis, R. J. (2014). Toxicology of ciguatoxins. Toxins and biologically active compounds from microalgae: Volume 2: biological effects and risk management. (pp. xx-xx) Boca Raton, FL, United States: CRC Press.

  • Dutertre, Sebastien and Lewis, Richard J. (2013). Cone snail biology, bioprospecting and conservation. Snails: biology, ecology and conservation. (pp. 85-104) edited by Emil M. Hämäläinen and Sofia Järvinen. New York, NY, United States: Nova Science Publishers.

  • Wingerd, Joshua S., Vetter, Irina and Lewis, Richard J. (2012). Voltage-gated sodium channels as therapeutic targets.. Therapeutic targets: Modulation, Inhibition and Activation.. (pp. 63-122) edited by Luis M. Botana and Mabel Loza. Hoboken NJ, United States: John Wiley and Sons.

  • Vetter, Irina and Lewis, Richard J. (2011). Natural product ligands of TRP channels. Transient receptor potential channels. (pp. 41-85) edited by Md. Shahidul Islam. New York, United States: Springer. doi: 10.1007/978-94-007-0265-3_3

  • Lewis, R. J. (2009). Conotoxins: molecular and therapeutic targets. Marine toxins as research tools (Progress in Molecular and Subcellular Biology). (pp. 45-66) edited by N. Fusetani. Berlin: Springer Verlag.

  • Schroeder, C. I., Lewis, R. J. and Adams, D. J. (2005). Block of voltage-gated calcium channels by peptide toxins. Voltage-Gated Calcium Channels. (pp. 294-308) edited by Gerald W. Zamponi. New York, U.S.A.: Springer US. doi: 10.1007/0-387-27526-6_19

  • Lewis, R. J. (2003). Detection of toxins associated with cigutera fish poisoning. Manual on Harmful Marine Microalgae. (pp. 267-277) edited by Hallegraeff, G M; Anderson, D M; Cembella and A D. Landais, France: UNESCO Publishing.

  • Holmes, M.J. and Lewis, R. J. (2002). Toxin-producting dinoflagellates. Perspectives in Molecular Toxinology. (pp. 39-65) edited by Andre Menez. England: John Wiley & sons Ltd.

  • Fenner, P. and Lewis, R. J. (2001). Ciguatera (fish poisoning). Channelopathies of the nervous sytstem. (pp. 295-307) edited by Michael Rose and Robert C. Griggs. USA: Butterworth Heinemann.

  • Lewis, Richard J., Molgo, Jordi and Adams, David J. (2000). Ciguatera toxins: Pharmacology of toxins involved in Ciguatera and related fish poisonings. Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection. (pp. 419-447) edited by Luis M. Botana. New York: Marcel Dekker Inc..

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

Completed Supervision