Professor Nicholas Casewell

Head of Centre for Snakebite Research & Interventions, Chair in Tropical Disease Biology & Wellcome Trust Research Fellow

Areas of interest

Characterising the functional activity of venoms and developing new treatments to combat pathologies caused by envenoming. Reconstructing the evolutionary history of venom systems and their toxic components to understand the molecular basis for such adaptations and ensuing variation in venom composition. Utilising ‘omic’ data to investigate the relationship between the genome, transcriptomes, and proteomes of venomous animals and how this relates to venom production. Investigating how snake venom variation impacts upon antivenom therapy. Testing the immunological cross-reactivity, safety, stability and efficacy of snake antivenoms and the development of novel methods for their manufacture. Screening, selecting and validating small molecule toxin inhibitors as new snakebite therapies.

Background

Professor Casewell is a graduate of the University of Liverpool (BSc Tropical Disease Biology), during which time he also studied at the Liverpool School of Tropical Medicine. Casewell’s interest in snake venom research developed at this point, ultimately resulting in a PhD studentship at Bangor University where he studied the composition, evolution and immunology of saw-scaled viper venoms and their antivenoms. The result of Professor Casewell’s PhD research saw him nominated as a finalist for the Society for Molecular Biology and Evolution’s young researcher prize, the Walter M. Fitch Award, in 2011. Subsequently, Casewell became Antivenom Manager for the UK manufacturing company MicroPharm Limited, in a commercial and academic collaboration with the Liverpool School of Tropical Medicine.

In 2012, Casewell was awarded an Independent Research Fellowship from the Natural Environment Research Council, UK to investigate the evolution and composition of different fish venoms, returning to Bangor University to conduct the research.

In 2014, Casewell was appointed as a Lecturer at the Liverpool School of Tropical Medicine and, subsequently, as a Senior Lecturer in 2016.

In 2016 Professor Casewell was awarded a Sir Henry Dale Research Fellowship by the Wellcome Trust and Royal Society to develop new treatments for tropical snakebite.

In 2019, Professor Casewell was appointed to a proleptic Chair in Tropical Disease Biology by the Liverpool School of Tropical Medicine.

Professor Casewell has published over 70 scientific papers on venoms and antivenoms, and he serves on the editorial board of the scientific journals Toxins and PLOS Neglected Tropical Diseases. His scientific research is funded by the Wellcome Trust, the Royal Society, the Medical Research Council, DFID, and NIHR.

Research

Professor Casewell’s research focus is to understand the mechanisms by which variation in venom (toxin) composition are generated, and how this variation can be circumvented during the development of new therapeutics for snakebite. Toxin characterisation work involves applying ‘omic’ technologies (genomics, transcriptomics, proteomics) to:

(i) investigate the evolutionary history of venom in different animal lineages,
(ii) detect venom variation at different taxonomic levels and
(iii) investigate the processes that alter the transcription and translation of toxin gene loci.

Such studies have included the publication of the first snake genomes. Professor Casewell’s therapeutic research focuses on using venom compositional information to rationally develop, select and validate the efficacy of new therapeutics for combatting the pathologies caused by medically important snakes. These approaches include the use of conventional antibody therapies, as well as novel approaches using small molecule toxin inhibitors, decoy receptor molecules, and monoclonal antibodies. This therapeutic research is underpinned by the development and application of a variety of bioassays relevant to toxins that cause medically relevant pathologies. Most recently, Professor Casewell has begun using clinical samples from snakebite victims to better understand how snakebite pathology develops over time, and to assess how effective current treatments are

Public engagement/Media 

Featured in the Wellcome Trust’s month of celebrating scientists “advancing ideas”. November 2016.

Wellcome Trust video interview about my science public engagement work. July 2016. 

Assisted BBC Earth Unplugged video short on venom blood clotting. April 2016. 

Interview about antivenom shortages in Africa. BBC News TV, Radio and website. September 2015.

Interview about snakebite for a forthcoming feature TV documentary. September 2015.

Interview and venom demonstration for BBC World’s “Health Check” TV programme. Aired August 2015.

Scientific advisor for the science communication animation website  “Stated Clearly”. 2014-present. 

Interviewed by Science for a “news focus” piece entitled “Secrets of Snakes” and by New Scientist for a feature article called “Under the Hood” about my research on snake genomics. December 2013 and January 2014.

Recent publications: 

    Selected publications

    • 2020

      Post Y, Puschhof J, Beumer J, Kerkkamp HM, de Bakker MAG, Slagboom J, de Barbanson B, Wevers NR, Spijkers XM, Olivier T, Kazandijan T, Ainsworth S, Iglesias CL, van de Wetering WJ, Heinz MC, van Ineveld RL, van Kleef RDGM, Begthel H, Korving J, Bar-Ephraim YW, Getreuer W, Rios AC, Westerink RHS, Snippert HJG, van Oudenaarden A, Peters PJ, Vonk FJ, Kool J, Richardson MK, Casewell NR,  Clevers H. 2020. Snake venom gland organoids. Cell. 80(2), 233-247. doi: 10.1016/j.cell.2019.11.038.

      Hamilton BR, Marshall DL, Casewell NR, Harrison RA, Blanksby SJ, Undheim EAB. 2020. Mapping enzyme activity on tissue by functional mass spectrometry imaging. Angew. Chem. Int. Ed. In press. doi: 10.1002/anie.201911390

      2019

      Casewell NR, Petras D, Card DC, Suranse V, Mychajliw AM, Richards D, Koludarov I, Albulescu O-A, Slagboom J, Hempel B-F, Ngum NM, Kennerley RJ, Brocca JL, Whiteley G, Harrison RA, Bolton FMS, Debono J, Vonk FJ, Alföldi J, Johnson J, Karlsson E, Lindblad-Toh K, Mellor IR, Süssmuth RD, Fry BG, Kuruppu S, Hodgson WC, Kool J, Castoe TA, Barnes I, Sunagar K, Undheim EAB, Turvey ST. 2019. Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals. Proc. Natl. Acad. Sci. USA. 116(51), 25745-25755. doi: 10.1073/pnas.1906117.

      Chaisakul J, Alsolaiss J, Charoenpitakchai M, Wiwatwarayos K, Sookprasert N, Harrison RA, Chaiyabutr N, Chanhome L, Tan CH, Casewell NR. Evaluation of the geographical utility of Eastern Russell’s viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity. PLOS Neglected Tropical Diseases. 13(10), e0007338. doi: 10.1371/journal.pntd.0007338.

      Albulescu L-O, Kazandjian T, Slagboom J, Bruyneel B, Ainsworth SA, Al Solaiss J, Wagstaff SC, Harrison RA, Ulens C, Kool J, Casewell NR. 2019. A decoy-receptor approach using nicotinic acetylcholine receptor mimics reveals the potential of AChBPs as therapeutics against neurotoxic snakebite. Frontiers in Pharmacology. 10, 848.doi: 10.3389/fphar.2019.00848.

      2018

      Marshall BM, Casewell NR, Vences M, Glaw F, Andreone F, Rakotoarison A, Zancolli G, Woog F, Wüster W. 2018. Widespread vulnerability of Malagasy predators to the toxins of an introduced toad. Current Biology.28, R654-R655. doi:10.1016/j.cub.2018.04.024.

      Ainsworth S, Slagboom J, Alomran N, Pla D, Alhamdi Y, King SI, Bolton FMS, Gutierrez JM, Vonk FJ, Toh C-H, Calvete JJ, Kool J, Harrison RA, Casewell NR. 2018. The paraspecific neutralisation of snake venom-induced coagulopathy by antivenoms. Communications Biology. 1, 34.doi: 10.1038/s42003-018-0039-1.

      Ainsworth S, Petras D, Engmark M, Süssmuth RD, Whiteley G, Albulescu L-O, Kazandjian T, Wagstaff SC, Rowley P, Wüster W, Dorrestein PC, Harrison RA, Casewell NR, Calvete JJ. 2018. The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and binding to available antivenoms. Journal of Proteomics.172, 173-189. doi: 10.1016/j.jprot.2017.08.016. 

      2017

      Harrison RA, Oluoch GO, Ainsworth S, Al Solaiss J, Bolton F, Arias A-S, Gutierrez J-M, Rowley P, Kalya S, Ozwara H, Casewell NR. 2017. Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. PLOS Neglected Tropical Diseases.11, e0005969.doi: 10.1371/journal.pntd.0005969.

      Casewell NR*, Visser JC*, Baumann K*, Dobson J*, Han H*, Kuruppu S, Morgan M, Romilio A, Weisbecker V, Ali SA, Debono J, Koludarov I, Que I, Bird GC, Cooke GM, Nouwens A, Hodgson WC, Wagstaff SC, Cheney KL, Vetter I, van der Weerd L, Richardson MK, Fry BG. 2017. The evolution of fangs, venom and mimicry systems in blenny fishes. Current Biology. 27, 1184-1191. doi: 10.1016/j.cub.2017.02.067. *these authors contributed equally.

      Slagboom J, Kool J, Harrison RA, Casewell NR. 2017. Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise. British Journal of Haematology. 177,947-959. doi: 10.1111/bjh.14591.

      Pla D, Sanz L, Whiteley G, Wagstaff SC, Harrison RA, Casewell NR, Calvete JJ. 2017. What killed Karl Patterson Schmidt? Combined venom gland transcriptomic, venomic and antivenomic analysis of the South African green tree snake (the boomslang), Dispholidus typus. Biochimica et Biophysica Acta (BBA) – General Subjects. 1861(4), 814-823. doi: 10.1016/j.bbagen.2017.01.020.

      2016  

      Casewell NR. 2016. Venom evolution: gene loss shapes phenotypic adaptation. Current Biology. 26, R849-R851. doi: 10.1016/j.cub.2016.07.082. Dispatch.

      Simões BF, Sampaio FL, Douglas RH, Kodandaramaiah U, Casewell NR, Harrison RA, Hart NS, Partridge JC, Hunt DM, Gower DJ. 2016. Visual pigments, ocular filters and the evolution of snake vision. Molecular Biology and Evolution. 33(10), 2483-2495. doi: 10.1093/molbev/msw148.

      Whiteley G, Logan RAE, Leung K-YD, Newberry FJ, Rowley PD, Dunbar JP, Wagstaff SC, Casewell NR, Harrison RA. 2016. Stabilising the integrity of snake venom mRNA stored under tropical field conditions expands research horizons. PLOS Neglected Tropical Diseases.10(6), e0004615. doi:10.1371/journal.pntd.0004615.

      2015 

      Ujvari B*, Casewell NR*, Sunagar K*, Arbuckle K, Wüster W, Lo N, O’Meally D, Beckmann C, King GF, Deplazes E, Madsen T. 2015. Widespread convergence in toxin resistance by predictable molecular evolution. Proc. Natl. Acad. Sci. USA. In press. *these authors contributed equally.

      Jouiaei M*, Casewell NR*, Yanagihara AA, Nouwens A, Cribb BW, Whitehead D, Jackson TNW, Ali SA, Wagstaff SC, Koludarov I, Alewood P, Hansen J, Fry BG. 2015. Firing the sting: chemical discharge of cnidae reveals novel proteins and peptides from box jellyfish (Chironex fleckeri) venom. Toxins.7, 936-950. doi: 10.3390/toxins7030936. *these authors contributed equally.

      Junqueira-de-Azevado ILM, Val Bastos CM, Ho PL, Luna MS, Yamanouye N, Casewell NR. 2015. Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom. Molecular Biology and Evolution. 32(3), 754-766. doi: 10.1093/molbev/msu337.

      Reyes-Velasco J, Card DC, Andrew AL, Shaney KJ, Adams RH, Schield DR, Casewell NR, Mackessy SP, Castoe TA. 2015. Expression of venom gene homologs in diverse python tissues suggests a new model for the evolution of snake venom. Molecular Biology and Evolution. 32(1), 173-183. doi: 10.1093/molbev/msu294.

      Lecht S, Ciaverelli RA, Gerstenhaber J, Calvete JJ, Lazarovici P, Casewell NR, Harrison R, Lelkes PI, Marcinkiewicz C. 2015. Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki. Biochimica et Biophysica Acta (BBA) – General Subjects. 1850(6), 1169-1179. doi: 10.1016/j.bbagen.2015.02.002.

      Ali SA, Jackson TNW, Casewell NR, Low DHW, Rossi S, Baumann K, Fathinia B, Visser J, Nouwens A, Hendrikx I, Jones A, Undheim E, Fry BG. 2015. Extreme venom variation in Middle Eastern vipers: a proteomics comparison of Eristicophis macmahonii, Pseudocerastes fieldi and Pseudocerastes persicus. Journal of Proteomics. 116, 106-113. doi: 10.1016/j.prot.2014.09.003. 

      2014 

      Casewell NR, Wagstaff SC, Wüster W, Cook DAN, Bolton FMS, King SI, Pla D, Sanz L, Calvete JJ, Harrison RA. 2014. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proc. Natl. Acad. Sci. USA. 111(25), 9205-9210. doi: 10.1073/pnas.1405484111. Cover article.

      Archer J, Whiteley G, Casewell NR, Harrison RA, Wagstaff SC. 2014. VTBuilder – a tool for the assembly of variant transcriptomes. BMC Bioinformatics. 15, 389. doi: 10.1186/s12859-014-0389-8.

      Casewell NR, Al-Abdulla I, Smith D, Coxon R, Landon J. 2014. Immunological cross-reactivity and neutralisation of European adder venoms with the monospecific Vipera berus antivenom ViperaTAb. Toxins. 6(8), 2471-2482. doi: 10.3390/toxins6082471.

      Baumann K*, Casewell NR*, Ali SA, Jackson TNW, Vetter I, Dobson JS, Cutmore SC, Nouwens A, Lavergne V, Fry BG. 2014. A ray of venom: combined proteomic and transcriptomic investigation of fish venom composition using barb tissue from the blue-spotted stingray (Neotrygon kuhlii). Journal of Proteomics. 109C, 188-198. doi: 10.1016/j.prot.2014.06.004. *these authors contributed equally.

      Bolton FMS, Casewell NR, Al-Abdulla I, Price-Jones R, Landon J. 2014. Production and assessment of ovine antisera for the manufacture of a veterinary antivenom. Veterinary Record. 174(16), 406. doi: 10.1136/vr.102286.

      Jesupret C, Jackson TNW, Ali SA, Baumann K, Yang D, Greisman L, Kern L, Casewell NR, Undheim EAB, Koludarov I, Debono J, Low DHW, Rossi S, Panagides N, Winters K, Ignjatovic V, Summerhayes R, Jones A, Nouwens A, Dunstan N, Hodgson WC, Winkel K, Monagle P, Fry BG. 2014. Vintage venoms: proteomic and pharmacological stability of snake venoms stored for up to eighty years. Journal of Proteomics. 105, 285-294. doi: 10.1016/j.prot.2014.01.004.

      Al-Abdulla I, Casewell NR, Landon J. 2014. Single-reagent one-step procedures for the purification of ovine IgG, F(ab’)2 and Fab antivenoms by caprylic acid. Journal of Immunological Methods. 402, 15-22. doi: 0.1016/j.jim.2013.11.00119. 

      2013 

      Vonk FJ*, Casewell NR*, Henkel CV, Heimburg A, Jansen HJ, McCleary RJR, Kerkkamp HME, Vos R, Guerreiro I, Calvete JJ, Wüster W, Woods AE, Logan JM, Harrison RA, Castoe TA, de Koning APJ, Pollock DD, Renjifo C, Currier RB, Salgado D, Pla D, Sanz L, Hyder AS, Ribeiro JMC, Arntzen JW, van den Thillart GEEJ, Boetzer M, Pirovano W, Dirks RP, Spaink HP, Duboule D, McGlinn E, Kini RM, Richardson MK. 2013. The king cobra genome reveals dynamic evolution and adaptation in the snake venom system. Proc. Natl. Acad. Sci. USA. 110(51), 20651-20656. doi: 10.1073/pnas.1314702110. Cover article. *these authors contributed equally.

      Castoe TA, de Koning APJ, Hall KT, Card DC, Schield DR, Fujita MK, Ruggiero RP, Degner JF, Daza JM, Gu W, Reyes-Velasco J, Shaney KJ, Castoe JM, Fox SE, Poole AW, Polanco D, Dobry J, Vandewege MW, Li Q, Schott R, Kapusta A, Minx P, Feschotte C, Uetz P, Ray DA, Hoffman F, Bogden R, Smith EN, Chang BSW, Vonk FJ, Casewell NR, Henkel C, Richardson MK, Mackessy SP, Bronikowski AM, Yandell M, Warren WC, Secor SM, Pollock DD. 2013. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes. Proc. Natl. Acad. Sci. USA. 110(51), 20645-20650. doi: 10.1073/pnas.1314475110.

      Casewell NR, Wüster W, Vonk FJ, Harrison RA, Fry BG. 2013. Complex cocktails: the evolutionary novelty of venoms. Trends in Ecology & Evolution 28, 219-229.doi: 10.1016/j.tree.2012.10.020.  Cover article.

      Brust A, Sunagar K, Undheim EAB, Vetter I, Yang D, Casewell NR, Ruder T, Jackson TNW, Koludarov I, Alewood PF, Hodgson WC, Lewis RJ, King GF, Antunes A, Hendrikx I, Fry BG. 2013. Differential evolution of domains: comparative evolution of Psammophis and Echis snake venom metalloproteinases (SVMP). Molecular & Cellular Proteomics12, 651-663. doi: 10.1074/mcp.m112.023135.

      Sunagar K, Fry BG, Jackson TNW, Casewell NR, Undheim EAB, Vidal N, Ali SA, King GF, Vasudevan K, Vasconcelos V, Antunes A. 2013. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenal. PLoS ONE.8(11), e81827. doi: 10.1371/journal.pone.0081827.

      Al-Abdulla I, Casewell NR, Landon J. 2013. Long-term physicochemical and immunological stability of a liquid formulated intact ovine immunoglobulin-based antivenom. Toxicon 64, 38-42.doi: 10.1016/j.toxicon.2012.12.022.

      Conlon JM, Attoub S, Arafat H, Mechkarska M, Casewell NR, Harrison RA, Calvete JJ. 2013. Cytotoxic activities of [Ser49] phospholipase A2 from the venom of the saw-scaled vipers Echis ocellatus, E. coloratus, E. pyramidum leakeyi, E. carinatus sochureki. Toxicon71, 96-104. doi: 10.1016/j.toxicon.2013.05.017. 

      2012 

      Casewell NR, Huttley GA,Wüster W. 2012. Dynamic evolution of venom proteins in squamate reptiles. Nature Communications 3, 1066. doi: 10.1038/ncomms2065.

      Casewell NR. 2012.On the ancestral recruitment of metalloproteinases into the venom of snakes. Toxicon60(4), 449-454. doi: 10.1016/j.toxicon.2012.02.006.

      Fry BG, Scheib H, Junqueira-de-Azevado ILM, Silva DA, Casewell NR. 2012. Novel transcripts in the maxillary venom glands of advanced snakes. Toxicon 59(7-8), 696-708.

      Fry BG, Casewell NR, Wüster W, Vidal N, Young B, Jackson T. 2012. The structural and functional diversification of the Toxicoferan reptile venom system. Toxicon60(4), 434-448. doi: 10.1016/j.toxicon.2012.02.013. 

      2011 

      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 & Evolution 28(9), 2637-2649. doi: 10.1093/molbev/msr091.

      Casewell NR, Wagstaff SC, Harrison RA, Wüster W. 2011. Gene tree parsimony of multi-locus snake venom protein families reveals species tree conflict as a result of multiple parallel gene loss. Molecular Biology & Evolution 28(3), 91-110. doi: 10/1093/molbev/msq302. 

      Harrison RA, Cook DA, Renjifo C, Casewell NR, Currier RB, Wagstaff SC. 2011. Research strategies to improve snakebite treatment: challenges and progress. Journal of Proteomics 74(9), 1768-1780. doi: 10.1016/j.jprot.2011.06.019.

      Williams DJ, Gutiérrez J-M, Calvete JJ, Wüster W, Ratanabanangkoon K, Paiva O, Brown N, Casewell NR, Harrison RA, Rowley P, Jensen SD, Winkel KD, Warrell DA. 2011. Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa.  Journal of Proteomics 74(9), 1735-1767. doi: 10.1016/j.jprot.2011.05.027. 

      2010 

      Casewell NR, Cook DAN, Wagstaff SC, Nasidi A, Durfa N, Wüster W, Harrison RA. 2010. Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom. PLoS Neglected Tropical Diseases 4(10),e851. doi:10.1371/journal.pntd.0000851. 

      2009 

      Casewell NR, Harrison RA, Wüster W, 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 Genomics10, 564. doi:10.1186/1471-2164-10-564. 

      Book Chapters:

      Casewell NR, Sunagar K, Takacs Z, Calvete JJ, Jackson TNW, Fry BG. 2015. Snake venom metalloprotease enzymes. pp. 347-363. In: Fry BG (Editor), Venomous reptiles & their toxins: evolution, pathophysiology and biodiscovery. Oxford University Press, New York, USA. ISBN: 978-0199309399.

      Fry BG, Sunagar K, Casewell NR, Kochva E, Roelants K, Scheib H, Wüster W, Vidal N, Young B, Burbrink F, Pyron RA, Vonk FJ, Jackson TNW. 2015. The origin and evolution of the Toxicofera reptile venom system. pp. 1-31. In: Fry BG (Editor), Venomous reptiles & their toxins: evolution, pathophysiology and biodiscovery. Oxford University Press, New York, USA. ISBN: 978-0199309399.

      Fry BG, Undheim EAB, Jackson TNW, Georgieva D, Vetter I, Calvete JJ, Scheib H, Cribb BW, Yang DC, Daly NL, Manchadi MLR, Gutiérrez JM, Roelants K, Lomonte B, Nicholson GM, Dziemborowicz S, Lavergne V, Ragnarsson L, Rash LD, Mobli M, Hodgson WC, Casewell NR, Nouwens A, Wagstaff SC, Ali SA, Whitehead DL, Herzig V, Monagle P, Kurniawan ND, Reeks T, Sunagar K. 2015. Research methods. pp. 153-214. In: Fry BG (Editor), Venomous reptiles & their toxins: evolution, pathophysiology and biodiscovery. Oxford University Press, New York, USA. ISBN: 978-0199309399.

      Fry BG, Koludarov I, Jackson TNW, Holford M, Terrat Y, Casewell NR, Undheim EAB, Vetter I, Ali SA, Low DHW, Sunagar K. 2015. Seeing the woods for the trees: understanding venom evolution as a guide for biodiscovery. pp. 1-36. In: King GF (Editor), Venoms to drugs: venom as a source for the development of human therapeutics. Royal Society of Chemistry, Cambridge, UK. ISBN: 978-1849736633.

      Sunagar K, Casewell NR, Varma S, Kolla R, Antunes A, Moran Y. 2014. Deadly innovations: unraveling the molecular evolution of animal venoms. In: Gopalkrishnakone P (Editor), Calvete JJ (Section Editor), Venom Genomics and Proteomics, Handbooks of Toxinology. Springer Netherlands. doi: 10.1007/978-94-007-6649-5_27-1.