Contact information
Graham Davies
Head of Chemokine Technology Development
My research is focussed on discovering and developing new drugs that can be used to treat heart diseases where inflammation plays a major role. Through employing yeast surface display, a number of small proteins called evasins have been identified from tick saliva. These evasins have a unique “one-to-many” mechanism of action, i.e. they bind multiple chemokines, and potently block inflammation. The “one-to-many” action of the evasins overcomes the robustness of the chemokine system, which is unaffected by traditional anti-chemokine drugs that work on a “one-to-one” basis. Chemokines are produced by the body in response to injury/pathogens, resulting in the migration of white blood cells that can lead to inflammation. I have developed a number of techniques utilising high throughput flow cytometry to functionally validate the evasins. These include fluorescent ligand binding/competition assays and a raft of human and mouse primary cell migration assays. My current work is focussed on the development of the delivery of the evasins to sites of inflammation and the development of a phage peptide display technique to enable identification of evasin derived peptides that interact with chemokines.
Recent publications
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Discovery and pharmacophoric characterization of chemokine network inhibitors using phage-display, saturation mutagenesis and computational modelling
Journal article
Vales S. et al, (2023), Nature Communications, 14
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Transcriptomic Analysis of Inflammatory Cardiomyopathy Identifies Molecular Signatures of Disease and Informs in silico Prediction of a Network-Based Rationale for Therapy.
Journal article
Singh K. et al, (2021), Front Immunol, 12
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Engineered anti-inflammatory peptides inspired by mapping an evasin-chemokine interaction.
Journal article
Darlot B. et al, (2020), J Biol Chem, 295, 10926 - 10939
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A knottin scaffold directs the CXC-chemokine-binding specificity of tick evasins
Journal article
LEE A. et al, (2019), Journal of Biological Chemistry
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Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets.
Journal article
Alenazi Y. et al, (2018), Scientific reports, 8, 6333 - 6333
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The N-terminal domain of a tick evasin is critical for chemokine binding and neutralization and confers specific binding activity to other evasins
Journal article
Eaton J. et al, (2018), Journal of Biological Chemistry
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Yeast surface display identifies a family of evasins from ticks with novel polyvalent CC chemokine-binding activities.
Journal article
Singh K. et al, (2017), Sci Rep, 7, 4267 - 4267