51cg

Dr Caroline Barelle

Dr Caroline Barelle
Dr Caroline Barelle
Dr Caroline Barelle

MBA

Honorary Lecturer

51cg
Office Address

Office 22a School of Medical Sciences 51cg Liberty Building Foresterhill AB25 2ZP

School/Department
School of Medicine, Medical Sciences and Nutrition

Biography

I currently lead a team of senior scientists at the 51cg 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 51cg and I am currently completing a MBA at Robert Gordon’s University, Business School.

Research

Research Overview

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.  

Current Research

The VNAR Development team:

Senior Scientists:

Dr Marina Kovaleva (ex-Pfizer, Wyeth, Haptogen)

Mr John Steven (ex-Pfizer, Wyeth, Haptogen)

Dr Laura Ferguson (ex-Pfizer)

Dr Nachiket Shembekar

Mohammed Al Qaraghuli (BSc)

PhD Students:

Obinna Ubah

Magdalena Buschhaus

Publications

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  • A rationally designed novel bi-functional human TNF-α and Janus Kinase targeted soloMER® Drug Conjugate (SDC) with a neutrophil elastase cleavable linker delivering inflammation site-specific release of payload

    Murray, E., Priyanka, S., Martinez Fraile, J., Grygorash, R., Idress, M. S., Brownbridge, L., Glavina, S., Camper, N., Boyd, R., Porter, A., Barelle, C., Ubah, O.
    Journal of Medicinal Chemistry, vol. 69, no. 8, pp. 9664–9679
    Contributions to Journals: Articles
  • The structural basis for the selective antagonism of soluble TNF-alpha by variable new antigen receptors

    Ubah, O., Lake, E. W., Ott, K., Priyanka, S., Celeda, S., Gunaratne, G. S., West, J., Shi, K., Moeller, N. H., Porter, A., Aihara, H., Kosoff, D., LeBeau, A. M., Barelle, C.
    Nature Communications, vol. 17, 256
    Contributions to Journals: Articles
  • Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography

    Ubah, O. C., Lake, E. W., Gunaratne, G. S., Gallant, J. P., Fernie, M., Robertson, A. J., Marchant, J. S., Bold, T. D., Langlois, R. A., Matchett, W. E., Thiede, J. M., Shi, K., Yin, L., Moeller, N. H., Banerjee, S., Ferguson, L., Kovaleva, M., Porter, A. J., Aihara, H., LeBeau, A. M., Barelle, C. J.
    Nature Communications, vol. 12, no. 1, 7325
    Contributions to Journals: Articles
  • Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease

    Fraile, J. M., Palliyil, S., Barelle, C., Porter, A. J., Kovaleva, M.
    Drug design, development and therapy, vol. 15, pp. 3997-4009
    Contributions to Journals: Review articles
  • In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Constructs in a Mouse Model of Human RA: An Encouraging Milestone to Further Clinical Drug Development

    Ubah, O., Porter, A. J., Barelle, C. J.
    Journal of Immunology Research, vol. 2020, pp. 7283239
    Contributions to Journals: Articles
  • Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand

    Pepple, K. L., Wilson, L., Van Gelder, R. N., Kovaleva, M., Ubah, O. C., Steven, J., Barelle, C. J., Porter, A.
    Translational vision science & technology, vol. 8, no. 5, 11
    Contributions to Journals: Articles
  • Oriented attachment of VNAR proteins, Q2 via site-selective modification, on PLGA–PEG nanoparticles enhances nanoconjugate performance

    Nogueira, J. C. F., Greene, M. K., Richards, D. A., Furby, A. O., Steven, J., Porter, A., Barelle, C., Scott, C. J., Chudasama, V.
    Chemical Communications, vol. 55, no. 53, pp. 7671-7674
    Contributions to Journals: Articles
  • An Anti-hTNF-α Variable New Antigen Receptor Format Demonstrates Superior in vivo Preclinical Efficacy to Humira® in a Transgenic Mouse Autoimmune Polyarthritis Disease Model

    Ubah, O. C., Steven, J., Porter, A. J., Barelle, C. J.
    Frontiers in Immunology, vol. 10, 526
    Contributions to Journals: Articles
  • Next-generation flexible formats of VNAR domains expand the drug platform’s utility and developability

    Ubah, O. C., Buschhaus, M. J., Ferguson, L., Kovaleva, M., Steven, J., Porter, A. J., Barelle, C. J.
    Biochemical Society Transactions, vol. 46, no. 6, pp. 1559-1565
    Contributions to Journals: Review articles
  • Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralising Potency and Multifunctionality, Generated for Therapeutic Development

    Ubah, O. C., Steven, J., Kovaleva, M., Ferguson, L., Barelle, C., Porter, A. J. R., Barelle, C. J.
    Frontiers in Immunology, vol. 8, 1780
    Contributions to Journals: Articles
  • Phage Display Derived IgNAR V Region Binding Domains for Therapeutic Development

    Ubah, O. C., Barelle, C. J., Buschhaus, M. J., Porter, A. J.
    Current Pharmaceutical Design, vol. 22, no. 43, pp. 6519-6526
    Contributions to Journals: Articles
  • VNARs: An Ancient and Unique Repertoire of Molecules That Deliver Small, Soluble, Stable and High Affinity Binders of Proteins

    Barelle, C., Porter, A.
    Antibodies, vol. 4, no. 3, pp. 240-258
    Contributions to Journals: Articles
  • Structural insights and biomedical potential of IgNAR scaffolds from sharks

    Zielonka, S., Empting, M., Grzeschik, J., Könning, D., Barelle, C., Kolmar, H.
    mAbs, vol. 7, no. 1, pp. 15-25
    Contributions to Journals: Articles
  • ISOLATION OF THERAPEUTIC TARGET SPECIFIC VNAR DOMAINS TO ICOSL

    Barelle, C., Finlay, J. J. W., Darmanin-Sheehan, A.
    Patents: Patents
  • Shark variable new antigen receptor biologics: a novel technology platform for therapeutic drug development

    Kovaleva, M., Ferguson, L., Steven, J., Porter, A., Barelle, C.
    Expert opinion on biological therapy, vol. 14, no. 10, pp. 1527-1539
    Contributions to Journals: Articles
  • SINGLE DOMAIN BINDING MOLECULE

    Barelle, C., Muller, M., Calabro, V., Bikker, J., Steven, J., Tchistiakova, L., Kovalenko, O. V., Olland, A.
    Patents: Patents
  • Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis

    Kovalenko, O. V., Olland, A., Piché-Nicholas, N., Godbole, A., King, D., Svenson, K., Calabro, V., Müller, M. R., Barelle, C., Somers, W., Gill, D. S., Mosyak, L., Tchistiakova, L.
    The Journal of Biological Chemistry, vol. 288, no. 24, pp. 17408-17419
    Contributions to Journals: Articles
  • Generation and isolation of target-specific single-domain antibodies from shark immune repertoires

    Müller, M. R., O'Dwyer, R., Kovaleva, M., Rudkin, F., Dooley, H., Barelle, C.
    Methods in Molecular Biology: Antibody Engineering. Chames, P. (ed.). Humana Press, pp. 177-194, 18 pages
    Chapters in Books, Reports and Conference Proceedings: Chapters
  • Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias)

    Smith, L. E., Crouch, K., Cao, W., Müller, M. R., Wu, L., Steven, J., Lee, M., Liang, M., Flajnik, M. F., Shih, H. H., Barelle, C., Paulsen, J., Gill, D. S., Dooley, H.
    Developmental and Comparative Immunology, vol. 36, no. 4, pp. 665-679
    Contributions to Journals: Articles
  • Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain

    Müller, M. R., Saunders, K., Grace, C., Jin, M., Piche-Nicholas, N., Steven, J., O'Dwyer, R., Wu, L., Khetemenee, L., Vugmeyster, Y., Hickling, T. P., Tchistiakova, L., Olland, S., Gill, D., Jensen, A., Barelle, C.
    mAbs, vol. 4, no. 6, pp. 673-685
    Contributions to Journals: Articles
  • Shark novel antigen receptors: the next generation of biologic therapeutics?

    Barelle, C., Gill, D. S., Charlton, K.
    Pharmaceutical Biotechnology. Guzman, C. A., Feuerstein, G. Z. (eds.). Springer, pp. 49-62, 14 pages
    Chapters in Books, Reports and Conference Proceedings: Chapters
  • Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy

    Douglass, A., Wallace, K., Koruth, M., Barelle, C., Porter, A. J., Wright, M. C.
    Hepatology International, vol. 2, no. 4, pp. 405-15
    Contributions to Journals: Articles
  • Azole antifungals induce up-regulation of SAP4, SAP5 and SAP6 secreted proteinase genes in filamentous Candida albicans cells in vitro and in vivo

    Barelle, C., Duncan, V. M. S., Brown, A. J. P., Gow, N. A. R., Odds, F. C.
    Journal of Antimicrobial Chemotherapy, vol. 61, no. 2, pp. 315-322
    Contributions to Journals: Articles
  • Niche-specific regulation of central metabolic pathways in a fungal pathogen

    Barelle, C., Priest, C. L., MacCallum, D. M., Gow, N. A. R., Odds, F. C., Brown, A. J. P.
    Cellular Microbiology, vol. 8, no. 6, pp. 961-971
    Contributions to Journals: Articles
  • Candida albicans VAC8 is required for vacuolar inheritance and normal hyphal branching

    Barelle, C., Richard, M. L., Gaillardin, C., Gow, N. A. R., Brown, A. J. P.
    Eukaryotic Cell, vol. 5, no. 2, pp. 359-367
    Contributions to Journals: Articles
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