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Research & Innovation

McDonnell Laboratory

The McDonnell Laboratory studies the molecules and molecular interactions that control allergic and inflammatory immune responses. The group uses molecular, structural, biophysical and computational methods to elucidate the mechanisms of pathological immune responses. Based on the understanding of interaction mechanisms, the lab designs and develops inhibitors of molecular interactions, employing structure-based design and library screening approaches. Inhibitors are used both as investigative tools and developed further as novel immunotherapeutic agents.

Members

Anna Marie Davies

Research Fellow

James McDonnell

Professor of Molecular Immunology

Immunoglobulin E

Immunoglobulin E: structure, interactions and allostery

Immunoglobulin E (IgE) is the antibody isotype that mediates allergic immune reactions. For many years we have studied the IgE molecule, its three-dimensional structure and its interactions with other molecules. Recently, this work has led to the development of novel anti-IgE drugs for the treatment of allergic disorders.

scientist looking into microscope

The structure and function of immunoglobulin D

Immunoglobulin D (IgD) remains the most enigmatic of all antibody isotypes. Recent evidence indicate activity of IgD in the bronchial mucosa, and potential regulatory roles in allergy.

Immunoglobulin E

Interactions of IgE with parasite antigens

Although IgE is best known for its role in mediating allergic immune responses, its natural role is probably to rapidly rid the body of invading parasites. New research in the lab seeks to better understand the molecular interactions that control IgE-mediated anti-parasite immune responses.

Development of a point‐of‐care test for the detection of MDMA in latent fingerprints using Surface Plasmon Resonance and lateral flow technology
Pollard, C., Hudson, M., Mcdonnell, J. M., Royall, P. G. & Wolff, K., Apr 2022, In: Drug Testing And Analysis. 14, 4, p. 613-621 9 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1002/dta.3196
Reviving lost binding sites: Exploring calcium binding-site transitions between human and murine CD23
Ilkow, V., Davies, A. M., Dhaliwal, B., Beavil, A., Sutton, B. & McDonnell, J., Jul 2021, In: FEBS Open Bio. 11, 7, p. 1827-1840 14 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1002/2211-5463.13214
Nucleolin acts as the receptor for C1QTNF4 and supports C1QTNF4-mediated innate immunity modulation
Vester, S. K., Beavil, R. L., Lynham, S., Beavil, A. J., Cunninghame Graham, D. S., McDonnell, J. M. & Vyse, T. J., 1 Jan 2021, In: Journal of Biological Chemistry. 296, 100513. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1016/j.jbc.2021.100513
Rapid conjugation of antibodies to toxins to select candidates for the development of anticancer Antibody-Drug Conjugates (ADCs)
Hoffmann, R. M., Mele, S., Cheung, A., Larcombe-Young, D., Bucaite, G., Sachouli, E., Zlatareva, I., Morad, H. O. J., Marlow, R., McDonnell, J. M., Figini, M., Lacy, K. E., Tutt, A. J. N., Spicer, J. F., Thurston, D. E., Karagiannis, S. N. & Crescioli, S., 1 Jun 2020, In: Scientific Reports. 10, 1, p. 8869 8869. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1038/s41598-020-65860-x
Rapid conjugation of antibodies to toxins to select candidates for the development of anti-cancer Antibody-Drug Conjugates (ADCs)
Hoffmann, M., Mele, S., Cheung, A., Larcombe-Young, D., Bucaite, G., Sachouli, E., Zlatareva, I., Morad, H., Marlow, R., McDonnell, J., Figini, M., Lacy, K. E., Tutt, A., Spicer, J., Thurston, D., Karagiannis, S. N. & Crescioli, S., 1 Jun 2020, In: Scientific Reports. 10, 1, 22 p., 8869. Research output: Contribution to journal › Article › peer-review
NMR backbone assignment of the Cε4 domain of immunoglobulin E
Benjamin, S. V., Creeke, P. I., Henry, A. J. & McDonnell, J. M., 1 Apr 2020, In: Biomolecular NMR Assignments. 14, 1, p. 151-155 5 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1007/s12104-020-09936-9
Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization
Mitropoulou, A., Ceska, T., Heads, J., Beavil, A., Henry, A. J., McDonnell, J., Sutton, B. & Davies, A. M., 1 Mar 2020, In: Acta Crystallographica Section F:Structural Biology Communications. 76, p. 116-129 14 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1107/S2053230X20001466
Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human Patient–Derived IgE Antibodies
Bucaite, G., Kang-Pettinger, T., Moreira, J., Gould, H. J., James, L. K., Sutton, B. & McDonnell, J. M., 1 Oct 2019, In: Journal of Immunology. 203, 7, p. 1693-1700 8 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.4049/jimmunol.1900509
Anti-IgE Antibodies
Adams, R., Ceska, T. A., Davies, A. M., Henry, A. J., Liu, X., McDonnell, J. M., Sutton, B. J. & Westwood, M. K., 14 Dec 2017, Patent No. WO 2017/211928 A1, 8 Jun 2017, Priority date 10 Jun 2016, Priority No. 1610198.2 Research output: Patent
Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10
Dimeloe, S., Rice, L. V., Chen, H., Cheadle, C., Raynes, J., Pfeffer, P., Lavender, P., Richards, D. F., Nyon, M. P., Mcdonnell, J. M., Kemper, C., Gooptu, B. & Hawrylowicz, C. M., May 2019, In: Journal of Steroid Biochemistry and Molecular Biology. 189, p. 1-9 9 p., SBMB_2018_497. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1016/j.jsbmb.2019.01.014

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Our partners

Medical Research Council

Biotechnology and Biological Sciences Research Council (UKRI)

Asthma UK

Wellcome Trust

UCB Pharma

Asthma UK Centre in Allergic Mechanisms of Asthma

Group leads

Professor James McDonnell

Professor of Molecular Immunology

Contact us

james.mcdonnell@kcl.ac.uk

+44 (0)207 848 6970