Staff Profile: Dr Robert Harrison, B.Sc., M.Sc., Ph.D.
Appointment: Senior Lecturer, Head, Alistair Reid Venom Research Unit
Areas of interest: Rational design of new therapies to improve the treatment of the systemic effects of snake envenoming. Understanding the aetiology of, and identifying potential interventions for, the tissue necrotic effects of local envenoming. Molecular structure, evolution, biological activity and drug-discovery of snake venom proteins.
Born in Kenya, and a graduate of Nottingham University (BSc Zoology) and the London School of Hygiene and Tropical Medicine (MSc-Medical Parasitology; PhD-immunology of schistosomiasis), Harrison’s interests in the development of vaccines against schistosomiasis and onchocerciasis took him on various postdoctoral scientific adventures to Kenya, California and Egypt before he found a more permanent home in Liverpool. Now, leading the Alistair Reid Venom Research Unit and Senior Lecturer at the Liverpool School of Tropical Medicine, Harrison and his team conduct a variety of research activities with the objective to ‘improve the treatment of snakebite’. This includes the provision of antivenom to treat rural snakebite victims in Nigeria through a collaboration (the EchiTAb Study Group) with the Nigerian Federal Ministry of Health, the University of Oxford and antivenom producers in UK and Costa Rica. This collaboration has resulted in the provision of 34,000 vials of new antivenoms (17,000 life-saving treatments) to resolve the crisis in antivenom supply to Nigeria. Harrison is also am a member of the executive committee of the Global Snakebite Initiative which aims to raise the awareness of, and stimulate new funding to address the neglected problem of snakebite that primarily affects the most impoverished and geopolitically disadvantaged rural communities of Africa and Asia - who rarely have affordable access to effective healthcare.
Harrison’s research focus is to exploit advances in ‘high volume-high throughput’ gene and protein technologies to develop new antivenoms that are (i) more toxin-specific (to improve efficacy), (ii) more cross-generically effective (to improve geographical clinical utility), (iii) clinically safer and, for the first time, (iv) effective against the local tissue-destructive effects of envenoming. The intent is to design an antivenom-production system whose clinical and logistic improvements provide compelling incentives to international health agencies and commercial antivenom manufacturers to improve the delivery of effective, safe and affordable snakebite therapies to the rural poor African and Asian communities that most need it.
The group is also keen to harness the pharmacological potential of snake venom proteins to develop novel drugs for cardiovascular, cancer and neurological diseases. Our resources (venoms, venom gland EST data, toxin-specific antibodies) have also enrolled us in diverse collaborations involving venom toxin evolution, venom proteomics, antivenom production, pre-clinical and clinical assessment of new antivenoms.
- Secretary, European Section, International Society of Toxinology
- Member of Editorial Boards of Toxicon, J Venom Research, Guest Editor PLoS NTD
- Member, Antivenom Advisory Committee for the Public Health England
- Member, Scientific Steering Committee, Global Snakebite Initiative
- Expert Advisor, WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins
2014-2018 MRC Project Grant (MR/L01839X/1) “Novel immuno-proteomic strategies to develop a polyspecific, non-cold chain liquid snake antivenom with unparalleled sub-Saharan African efficacy” £771,224.RA Harrison (PI), Casewell, Calvete (Valencia), Gutierrez (San Jose).
2012-2015 Leverhulme Trust Project Grant (RPG-2012-627) “Has defence dictated the evolution of venom composition in spitting cobras” £209,171. RA Harrison, W Wuster (University of Bangor)
2012-2015 NC3R PhD Studentship “Refining, Reducing and Replacing in vivo WHO-standard preclinical assays of snake venom pathology and antivenom efficacy” £90,000. RA Harrison
2012-2015 Leverhulme Trust Project Grant (RPG-377) “Understanding the presence and prolonged stability of mRNA in venom” £183,000. SC Wagstaff, RA Harrison
2008-2011 BBSRC Project Grant “Elucidating the transcriptional and post-translational systems that regulate snake venom assembly and that control autolysis and self-toxicity” £316,000 RA Harrison, SC Wagstaff
Gutiérrez, José María, Burnouf, Thierry, Harrison, Robert, Calvete, Juan J, Kuch, Ulrich, Warrell, David A and Williams,, David J (2014) 'A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming'. Bulletin of the World Health Organization, Vol 92, Issue 7, pp. 526-532.
Casewell, Nicholas, Wagstaff, Simon, Wuster, W., Cook, Darren, Bolton, Fiona, King, Sarah, Pla, D., Sanz, L., Calvete, J. J. and Harrison, Robert (2014) 'Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms'. Proceedings of the National Academy of Sciences, Vol 111, Issue 25, pp. 9205-9210.
Vonk, F. J., Casewell, Nicholas, Henkel, C. V., Heimberg, A. M., Jansen, H. J., McCleary, R. J. R., Kerkkamp, H. M. E., Vos, R. A., Guerreiro, I., Calvete, J. J., Wuster, W., Woods, A. E., Logan, J. M., Harrison, Robert, Castoe, T. A., de Koning, A. P. J., Pollock, D. D., Yandell, M., Calderon, D., Renjifo, C., Currier, Rachel B., Salgado, D., Pla, D., Sanz, L., Hyder, A. S., Ribeiro, J. M. C., Arntzen, J. W., van den Thillart, G. E. E. J. M., Boetzer, M., Pirovano, W., Dirks, R. P., Spaink, H. P., Duboule, D., McGlinn, E., Kini, R. M. and Richardson, M. K. (2013) 'The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system'. Proceedings of the National Academy of Sciences, Vol 110, Issue 51, pp. 20651-20656.
Conlon, J Michael, Attoub, Samir, Arafat, Hama, Mechkarska, Milena, Casewell, Nicholas, Harrison, Robert and Calvete, Juan J (2013) 'Cytotoxic activities of [Ser⁴⁹]phospholipase A₂ from the venom of the saw-scaled vipers Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus.'. Toxicon, Vol 71, pp. 96-104.
Gutiérrez, José María, Warrell, David A, Williams, David J, Jensen, Simon, Brown, Nicholas, Calvete, Juan J and Harrison, Robert (2013) 'The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward.'. PLoS Neglected Tropical Diseases, Vol 7, Issue 6, e2162.
Casewell NR, Wagstaff SC, Wuster W, Cook DA, Bolton FM, King SI, Pla D, Sanz L, Calvete J, Harrison RA (2014) Medically important differences in snake venom composition are dictated by distinct post-genomic mechanisms. Proc. Natl. Acad. Sci. USA. 111(25):9017-9326.
Gutiérrez J-M, Burnouf T, Harrison RA, Calvete JJ, Kuch U, Warrell DA & Williams DJ, (2014) A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming, Bull WHO, In Press BLT.13.132431.
Vonk FJ, Casewell NR, Henkel CV, Heimburg A, Jansen HJ, McCleary RJR, Kerkkamp HME, Vos R, Guerreiro I, Calvete JJ, Wuster W, Woods AE, Logan JM, Harrison RA, et al. (2013) The king cobra genome reveals dynamic evolution and adaptation in the snake venom system. Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1313702110.
Conlon JM, Attoub S, Arafat H, Mechkarska M, Casewell NR, Harrison RA, Juan J. Calvete. (2013) Cytotoxic activities of [Ser49]phospholipase A2 from the venom of the saw-scaled vipers Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus Toxicon 71:96-104
Gutierrez J-M, Warrell DA, Williams DJ, Jensen S, Brown N, Calvete JJ, and Harrison RA. (2013) The need for full integration of snakebite envenoming within a global strategy to combat the Neglected Tropical Diseases: The way forward. PLoS Neglected Tropical Diseases, 7(6) e2162.
Casewell, NR, Wuster W, Vonk FJ, Harrison RA, Fry BG. (2013) Complex cocktails: the evolutionary novelty of venoms. Trends in Ecology and Evolution 28 (4):219-229.
Sanz L, Harrison RA, Calvete JJ. (2012) First draft of the genomic organization of a PIII-SVMP gene. Toxicon 60(4):455-69.
Harrison RA,Cook DA, Renjifo C,Casewell NR, Currier RB and Wagstaff SC. (2011) Research strategies to improve snakebite treatment: challenges and progress. Journal of Proteomics 74:1768-1780.
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.
Casewell NR, Wagstaff SC, Harrison RA, Renjifo C, Wüster W. (2011) Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes. Molecular Biology and Evolution. Doi:10.1093/molbev/msr091.
Petras, D., Sanz, L., Segura, A., Herrera, M., Villalta, M., Solano, D., Vargas, M., Leon, G., Warrell, D.A., Theakston, R.D.G., Harrison, R.A., Durfa, N., Nasidi, A., Gutierrez, J-M., Calvete, J.J. (2011) Snake venomics of the African spitting cobras: Toxin composition and assessment of congeneric cross-reactivity of the Pan-African EchiTAb-Plus-ICP antivenom by antivenomics and neutralization approaches. Journal of Proteomic Research 10:1266-1280.
Vaiyapuri S., Wagstaff, S.C., HarrisonR.A., Watson, K.A., GibbinsJ.M., and Hutchinson G. E. (2011) Evolutionary analysis of novel serine proteases in the venom gland transcriptome of Bitis gabonica rhinoceros. PLoS One 6(6):e21532.
Casewell NR, Wagstaff SC, Harrison RA, Wüster W (2010): Gene tree parsimony of multi-locus snake venom protein families reveals species tree conflict as a result of multiple parallel gene loss. Molecular Biology and Evolution,doi:10.1093/molbev/msq302.
Casewell, N.R., Cook, D.A.N., Wagstaff, S.C., Nasidi, A., Durfa, N., Wuster, W., and Harrison R.A. (2010) “Pre-clinical assays predict pan African Echis viper efficacy for a species-specific antivenom. PLoS Neglected Tropical Diseases, 4(10) e851.
Vaiyapuri S., Wagstaff, S.C., HarrisonR.A., Watson, K.A., GibbinsJ.M., and Hutchinson G. E. (2010) Purification and Functional Characterization of Rhiminopeptidase A, a Novel Aminopeptidase from the Venom of Bitis gabonica rhinoceros. PLOS Neglected Tropical Diseases 4(8):e796.
CalveteJ.J., Cid, P., Sanz, L., Segura A., Villalta M., Herrera M., León G., HarrisonR.A., Durfa N., NasidiA., CalveteJ.J., TheakstonR.D.G.T., Warrell D.A. and Gutiérrez J-M. (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(6):1194-1201
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.
Casewell, NR, Wuster W, Vonk FJ, Harrison RA, Fry BG. (2013) Complex cocktails: the evolutionary novelty of venoms. Trends in Ecology and Evolution 28 (4):219-229.
Harrison RA, Cook DA, Renjifo C,Casewell NR, Currier RB and Wagstaff SC. (2011) Research strategies to improve snakebite treatment: challenges and progress. Journal of Proteomics 74:1768-1780.
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.
Harrison, R.A. (2004) Development of venom toxin-specific antibodies by DNA immunisation: rationale and strategies to improve therapy of viper envenoming. Vaccine, Vol 22:1648-1655.