Dr Caroline Barelle
I currently lead a team of senior scientists at the University of Aberdeen developing shark single chain domains from initial lead isolation through to clinical candidate identification. Having successfully secured substantial pre-commercialisation funding, the focus is to take the lead VNAR domain, E06 (developed as a bio-tool for half-life extension) into the clinic and to strengthen the pipeline portfolio of oncology and anti-inflammatory products. Prior to setting up this team, I was Head of Shark IgNAR Development in Pfizer and Wyeth where I was responsible for establishing robust platforms for the isolation of these binding domains and progressing pipeline candidates. My first experience of developing shark domains was during my time with the antibody engineering spin-out company, Haptogen, where I was Programmes and Alliance manager. I obtained a PhD in biochemistry at the University of Aberdeen and I am currently completing a MBA at Robert Gordon’s University, Business School.
My research very much focuses on early stage biologic drug development from hit generation through to clinical candidate identification exploiting a naturally occurring single chain binding domain known as VNAR. These domains exist naturally in cartilaginous fish and play a role in the adaptive immune system of these animals. As such they can be isolated against specific disease targets both through immunization and semi-synthetic routes of selection. Their small size, high affinity for target, inherent solubility and stability make them very attractive as clinical drug candidates and the team are currently exploiting these attributes to build a strong pipeline portfolio of products.
The VNAR Development team:
Dr Marina Kovaleva (ex-Pfizer, Wyeth, Haptogen)
Mr John Steven (ex-Pfizer, Wyeth, Haptogen)
Dr Laura Ferguson (ex-Pfizer)
Dr Gerard Donohoe (ex-DCU, Merk-Millipore)
Dr Weili Guo (ex-DCU)
Contributions to Journals
- Kovalenko, OV., Olland, A., Piché-Nicholas, N., Godbole, A., King, D., Svenson, K., Calabro, V., Müller, MR., Barelle, CJ., Somers, W., Gill, DS., Mosyak, L. & Tchistiakova, L. (2013). 'Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis'. The journal of biological chemistry, vol 288, no. 24, pp. 17408-17419.
[Online] DOI: 10.1074/jbc.M112.435289
- Smith, LE., Crouch, K., Cao, W., Müller, MR., Wu, L., Steven, J., Lee, M., Liang, M., Flajnik, MF., Shih, HH., Barelle, CJ., Paulsen, J., Gill, DS. & Dooley, H. (2012). 'Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias)'. Developmental and Comparative Immunology, vol 36, no. 4, pp. 665-679.
[Online] DOI: 10.1016/j.dci.2011.10.007
- Müller, MR., Saunders, K., Grace, C., Jin, M., Piche-Nicholas, N., Steven, J., O'Dwyer, R., Wu, L., Khetemenee, L., Vugmeyster, Y., Hickling, TP., Tchistiakova, L., Olland, S., Gill, D., Jensen, A. & Barelle, CJ. (2012). 'Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain'. mAbs, vol 4, no. 6, pp. 673-685.
[Online] DOI: 10.4161/mabs.22242
- Douglass, A., Wallace, K., Koruth, M., Barelle, C., Porter, AJ., Wright, MC. & Barelle, CJ. (2008). 'Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy'. Hepatology International, vol 2, no. 4, pp. 405-15.
[Online] DOI: 10.1007/s12072-008-9093-y
- Barelle, CJ., Duncan, VMS., Brown, AJP., Gow, NAR. & Odds, FC. (2008). 'Azole antifungals induce up-regulation of SAP4, SAP5 and SAP6 secreted proteinase genes in filamentous Candida albicans cells in vitro and in vivo'. Journal of Antimicrobial Chemotherapy, vol 61, no. 2, pp. 315-322.
[Online] DOI: 10.1093/jac/dkm456
- Barelle, CJ., Richard, ML., Gaillardin, C., Gow, NAR. & Brown, AJP. (2006). 'Candida albicans VAC8 is required for vacuolar inheritance and normal hyphal branching'. Eukaryotic Cell, vol 5, no. 2, pp. 359-367.
[Online] DOI: 10.1128/EC.5.2.359-367.2006
- Barelle, C., Priest, CL., MacCallum, DM., Gow, NAR., Odds, FC. & Brown, AJP. (2006). 'Niche-specific regulation of central metabolic pathways in a fungal pathogen'. Cellular Microbiology, vol 8, no. 6, pp. 961-971.
[Online] DOI: 10.1111/j.1462-5822.2005.00676.x
[Online] AURA: Barelle_et_al_Niche_specific_regulation_2006.pdf
- Copping, VMS., Barelle, CJ., Hube, B., Gow, NAR., Brown, AJP. & Odds, FC. (2005). 'Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes'. Journal of Antimicrobial Chemotherapy, vol 55, no. 5, pp. 645-654.
[Online] DOI: 10.1093/jac/dki088
- Barelle, CJ., Manson, CL., MacCallum, DM., Odds, FC., Gow, NAR. & Brown, AJP. (2004). 'GFP as a quantitative reporter of gene regulation in Candida albicans'. Yeast, vol 21, no. 4, pp. 333-340.
[Online] DOI: 10.1002/yea.1099
- Murad, AMA., Lee, PR., Broadbent, ID., Barelle, CJ. & Brown, AJP. (2000). 'CIp10, an efficient and convenient integrating vector for Candida albicans'. Yeast, vol 16, no. 4, pp. 325-327.
[Online] DOI: 10.1002/1097-0061(20000315)16:4<325::AID-YEA538>3.0.CO;2-#
- Brown, AJ., Barelle, CJ., Budge, S., Duncan, J., Harris, S., Lee, PR., Leng, P., Macaskill, S., Abdul Murad, AM., Ramsdale, M., Wiltshire, C., Wishart, JA. & Gow, NA. (2000). 'Gene regulation during morphogenesis in Candida albicans'. Contributions to microbiology, vol 5, pp. 112-25.
- McWilliam, NA., Robbie, LA., Barelle, CJ., Adey, G., Prasad, S., Bennett, B. & Booth, NA. (1996). 'Evidence for an active fibrinolytic system in normal human bone marrow'. British Journal of Haematology, vol 93, no. 1, pp. 170-6.
Chapters in Books, Reports and Conference Proceedings
- Müller, MR., O'Dwyer, R., Kovaleva, M., Rudkin, F., Dooley, H. & Barelle, CJ. (2012). 'Generation and isolation of target-specific single-domain antibodies from shark immune repertoires'. in P Chames (ed.), Methods in Molecular Biology: Antibody Engineering. vol. 907, Methods and Protocols, Humana Press, pp. 177-194.
[Online] DOI: 10.1007/978-1-61779-974-7_9
- Barelle, C., Gill, DS. & Charlton, K. (2009). 'Shark novel antigen receptors: the next generation of biologic therapeutics?'. in CA Guzman & GZ Feuerstein (eds), Pharmaceutical Biotechnology. vol. 655, Advances in Experimental Medicine and Biology, vol. 655, Springer, New York, pp. 49-62.
[Online] DOI: 10.1007/978-1-4419-1132-2_6
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