Staff Profile: Robert Harrison
Dr Robert Harrison, B.Sc., M.Sc., Ph.D.
Appointment: Senior Lecturer, Head, Alistair Reid Venom Research Unit
Areas of interest: Molecular structure, evolution and biological activity of snake venom proteins; bioinformatic analysis of venom gland EST databases; rational design of antivenom to treat the systemic effects of snake envenoming; understanding the aetiology of, and identifying potential interventions for, the tissue necrotic effects of local envenoming.
Rob Harrison graduated in Zoology from Nottingham University (1977) and obtained his MSc (Medical Parasitology, 1978) and PhD (Helminthology, 1981) from the London School of Hygiene and Tropical Medicine. His interest in developing schistosome vaccines took him first to the Wellcome Trust Research Laboratory in Nairobi, Kenya, followed by a Wellcome Trust Advanced Training Fellowship in San Francisco (1984-1988) and then to the US Navy Medical Research Unit 3 in Cairo Egypt. He joined the Liverpool School of Tropical Medicine in 1994 on a project pioneering the use of DNA vaccination to engender protective immunity against Onchocerca volvulus and has, since 2000, focussed on snake venom research.
To improve the toxin-specificity and snake species cover of conventional antivenom treatment of systemic snake envenoming, we are constructing synthetic DNA and peptide immunogens. The latter are bioinfomatically designed, using venom gland EST data, to generate antibodies to neutralise the effects of the most pathogenic venom toxins of the most medically important snakes in West Africa. To address the inability of antivenom to reverse the necrotic effects of local envenoming, we are examining the therapeutic potential of (i) toxin-specific camelid VHH "nanobodies" and (ii) synthetic inhibitors of venom toxins. The group is also involved in harnessing the pharmacological potential of snake venom proteins to develop novel drugs for cardiovascular diseases. Our resources (venoms, venom gland EST data, toxin-specific antibodies) have enrolled us in diverse collaborations involving venom toxin evolution, venom proteomics, antivenom production, pre-clinical and clinical assessment of new antivenoms.
BBSRC (2008) Elucidating the transcriptional and post-translational systems that regulate snake venom assembly and that control autolysis and self-toxicity. RA Harrison and S Wagstaff.
MRC (2005) Development and preclinical assessment of recombinant snake venom toxin-specific nanobodies as a therapy against the local effects of envenoming. RA Harrison.
Leverhulme Trust Project Grant (2004) Genetic and morphological diversity in the medically important viper genus Echis. W Wuster, RDG Theakston, RA Harrison and C McCarthy.
Wellcome Trust Project Grant (2003) Bioinformatic and DNA immunisation strategies to generate neutralising antibodies specific to conserved haemostasis-disruptive toxins in African viper venoms. RA Harrison.
Currier, Rachel B, Calvete, Juan J, Sanz, Libia, Harrison, Robert, Rowley, Paul and Wagstaff, Simon (2012) 'Unusual stability of messenger RNA in snake venom reveals gene expression dynamics of venom replenishment.'. PLoS ONE, Vol 7, Issue 8, e41888.
Vaiyapuri, Sakthivel, Hutchinson, E Gail, Ali, Marfoua S, Dannoura, Abeer, Stanley, Ronald G, Harrison, Robert, Bicknell, Andrew B and Gibbins, Jonathan M (2012) 'Rhinocetin, a Venom-derived Integrin-specific Antagonist Inhibits Collagen-induced Platelet and Endothelial Cell Functions.'. The Journal of Biological Chemistry, Vol 287, Issue 31, pp. 26235-26244.
Fahmi, Laila, Makran, Bouchra, Pla, Davinia, Sanz, Libia, Oukkache, Naoual, Lkhider, Mustapha, Harrison, Robert, Ghalim, Noreddine and Calvete, Juan J (2012) 'Venomics and antivenomics profiles of North African Cerastes cerastes and C. vipera populations reveals a potentially important therapeutic weakness.'. Journal of proteomics, Vol 75, Issue 8, pp. 2442-53.
Casewell, Nicholas R., Wagstaff, Simon, Harrison, Robert, Renjifo, Camila and Wüster, Wolfgang (2011) 'Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes.'. Molecular biology and evolution, Vol 28, Issue 9, pp. 2637-2649.
Williams, David J, Gutiérrez, José-María, Calvete, Juan J, Wüster, Wolfgang, Ratanabanangkoon, Kavi, Paiva, Owen, Brown, Nicholas I, Casewell, Nicholas, Harrison, Robert, Rowley, Paul, O'Shea, Mark, Jensen, Simon D, Winkel, Kenneth D and Warrell, David A (2011) 'Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa.'. Journal of proteomics, Vol 74, Issue 9, pp. 1735-67.
Cook DA, Samarasekara CL, Wagstaff SC, Kinne J, Wernery U and Harrison RA (2010). Analysis of camelid IgG for antivenom development: Immunoreactivity and preclinical neutralisation of venom-induced pathology by IgG subclasses, and the effect of heat treatment. Toxicon [Epub ahead of print].
Cook DA, Owen T, Wagstaff SC, Kinne J, Wernery U and Harrison RA (2010). Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology. Toxicon [Epub ahead of print].
Cook DA, Owen T, Wagstaff SC, Kinne J, Wernery U and Harrison RA (2010). Analysis of camelid IgG for antivenom development: Serological responses of venom-immunised camels to prepare either monospecific or polyspecific antivenoms for West Africa. Toxicon [Epub ahead of print].
Calvete JJ, Cid P, Sanz L, Segura A, Villalta M, Herrera M, León G, Harrison R, Durfa N, Nasidi A, Theakston RD, Warrell DA and Gutiérrez JM (2010). Antivenomic assessment of the immunological reactivity of EchiTAb-Plus-ICP, an antivenom for the treatment of snakebite envenoming in sub-Saharan Africa. American Journal of Tropical Medicine and Hygiene 82: 1194-1201.
Vaiyapuri S, Harrison RA, Bicknell AB, Gibbins JM and Hutchinson G (2010). Purification and functional characterisation of Rhinocerase, a novel serine protease from the venom of Bitis gabonica rhinoceros. PLOS One 5(3): e9687.
Fasoli E, Sanz L, Wagstaff S, Harrison RA, Righetti PG and Calvete JJ (2010). Exploring the venom proteome of the African puff adder, Bitis arietans, using a combinatorial peptide ligand library approach at different pHs. Journal of Proteomics 73: 932-942.
Currier RB, Harrison RA, Rowley PD, Laing GD and Wagstaff SC (2010). Intra-specific variation in venom of the African Puff Adder (Bitis arietans): differential expression and activity of snake venom metalloproteinases (SVMPs). Toxicon 55: 864-873.
Segura A, Villalta M, Herrera M, León G, Harrison RA, Durfa N, Nasidi A, Calvete JJ, Theakston RDGT, Warrell DA and Gutiérrez J-M (2010). Preclinical assessment of the efficacy of a new antivenom (EchiTAb-Plus-ICPÒ) for the treatment of viper envenoming in sub-Saharan Africa. Toxicon 55: 369-374.
Harrison RA, Hargreaves A, Wagstaff SC, Faragher B and Lalloo DG (2009). Snake envenoming: a disease of poverty. PLoS Neglected Tropical Diseases 3: e569.
Casewell NR, Harrison RA, Wüster W and Wagstaff SC (2009). Comparative venom gland transcriptome surveys of the saw-scaled vipers (Viperidae: Echis) reveal substantial intra-family gene diversity and novel venom transcripts. BMC Genomics 10: 564.
Wagstaff SC, Sanz L, Juárez P, Harrison RA and Calvete JJ (2009). Combined snake venomics and venom gland transcriptomic analysis of the ocellated carpet viper, Echis ocellatus. Journal of Proteomics 71: 609-623.
Wagstaff SC, Favreau P, Cheneval O, Laing GD, Wilkinson MC, Miller R, Stocklin R and Harrison RA (2008). Molecular characterisation of endogenous snake venom metalloproteinase inhibitors. Biochemical and Biophysical Research Communications 365: 650-656.
Harrison R A, Ibison F, Wilbraham D, Wagstaff SC, Jones K, Donegan S and Lalloo D. Artesunate Versus Quinine for Treating Severe Malaria. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005967. DOI: 10.1002/14651858.CD005967.pub2.
Bazaa A, Juarez P, Marrakchi N, Bel Lasfer Z, El Ayeb M, Harrison RA, Calvete JJ and Sainz L (2007). Loss of introns along the evolutionary diversification pathway of snake venom disintegrins evidenced by sequence analysis of genomic DNA from Microvipera lebetina transmediterranea and Echis ocellatus. Journal of Molecular Evolution 64: 261-271.
Juarez P, Wagstaff SC, Sanz L, Harrison RA and Calvete J (2006). Molecular cloning of a Bitis arietans disintegrin-like domain, BA-5A, not expressed in the venom proteome. A putative intermediate in the evolution of the long disintegrin bitistatin. Journal of Molecular Evolution 63: 142-152.
Wagstaff SC and Harrison RA (2006). New insights into the mechanisms of Echis ocellatus envenoming by EST sequencing: identification of conserved integrin binding motifs in SVMPs and molecular characterisation of a new group of putative toxins, the renin-like aspartic proteases. Gene 377: 21-32.
Wagstaff SC, Laing GD, Theakston RDG, Papaspyridis C and Harrison RA (2006). Bioinformatics and multiepitope DNA immunization to design rational snake antivenom PLOS Medicine 3: 184.
Harrison RA, Hasson SS, Harmsen M, Laing GD, Conrath K and Theakston RDG (2006). Neutralisation of venom-induced haemorrhage by IgG from camels and llamas immunised with viper venom and also by endogenous, non-IgG components in camelid sera. Toxicon 47: 364-368.
Harrison RA (2004). Development of venom toxin-specific antibodies by DNA immunisation: rationale and strategies to improve therapy of viper envenoming. Vaccine 22: 1648-1655.
Harrison RA and Wernery U (2007). The unique properties of camelid IgG have potential to improve the treatment of snake bite. Journal of Camel Practice and Research 14: 15-16.