Karim Dib

    Karim Dib

    Senior Lecturer

    Phone: 028 90 972634, +44 (0)28 9097 2634

    For media contact email comms.office@qub.ac.uk
    or call +44(0)2890 973091.

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    Interests

    I am interested in signalling in Neutrophils

    Other

    I am a regular reviewer for various journals (Journal of Immunology, Journal of Leukocyte Biology, Journal of Biological Chemistry, Blood ...) providing my expertise in Leukocyte Biology.

    I also review grant proposals for UK-based funding bodies (MRC, BBSRC and The Wellcome Trust).

    Research Statement

    I lead a research group in Leukocyte Biology with a particular interest in neutrophils. We made the following discoveries:

    1- By using VASP KO mice, we found that VASP was a key regulator of Rap1 in neutrophils and platelets.  The regulation of Rap1 was controlled by phosphorylation of VASP by both cGMP-dependent kinases (cGKI) and cAMP-dependent protein kinase (PKA). In platelets, we idenfied the docking protein CrKL (which recruits C3G, a GEF for Rap1) as a novel binding partner of VASP. This finding challenged the concept of an exclusive calcium/CalDAG-dependent activation of Rap1 in platelets. We demonstarted that phosphorylation of VASP by PKA regulated the association between VASP and CrKL thus providing an explanation for the inhibition of Rap1 and platelet aggregation by agonists acting through PKA activation.

    2- We identified a novel protein interacting with L-selectin cytoplasmic tail, namely, the medium chain of the trans-Golgi network clathrin-associated protein complex AP1-mu1A. This protein is one of the four adaptin subunits of the adaptor-protein 1 (AP-1) complex. We proposed that phosphorylation of L-selectin tail on serine 364 (which occurs during in the inflammatory response) blocks AP-1-dependent retrograde transport of L-selectin (EE to TGN route of transport). Hence accumulation and clustering of L-selectin in endosomes and subsequently on the tips of microvilli to facilitate leukocyte tethering and rolling along the inflammed endothelium. This work was supported by the 7th Framework programme for Research of the European Commission (individual award).

     3- My group opened-up a new field of investigation by the discovery of a functional histamine four receptor (H4R) in human neutrophils with anti-inflammatory properties. This seminal work has been instrumental in securing an MRC-industry Asset Sharing Initiative grant to investigate whether bacterially produced histamine could represent a previously unappreciated evolutionarily conserved molecular dialog between bacteria and the host, whereby production of histamine would help infecting bacteria to counteract neutrophil anti-microbial functions. By using a cystic fibrosis animal model of disease, we are investigating whether blocking the H4R with a specific antagonist improves bacterial clearance in lungs.

     

    Teaching

    I teach Immunology for various course programmes.

    I am the coordinator of the SSC module entitled " conversational and Medical French". I teach medical students to take a medical history in French and to discuss medical articles in French.

    I am running practical classes in Immunology (ELISA, Western Blot, Immune cell isolation).

    Willingness to take PhD students

    Yes

    PhD projects

    Title of the project: To investigate the role of the histamine four receptor in the pathogenesis of chronic lung infections.
    We would like to test the hypothesis that accumulation of histamine in lung fluids impairs airways neutrophils in chronic lung diseases by engaging the histamine four receptor (H4R) in neutrophils. Engagement of the H4R may block the ability of neutrophils to kill pathogens. We will investigate whether H4R antagonists can be used to boost the anti-microbial functions of pulmonary neutrophils during chronic lung infections.

    Frequent Journals

    • Journal of Biological Chemistry

      ISSNs: 0021-9258

      Additional searchable ISSN (Electronic): 1083-351X

      American Society for Biochemistry and Molecular Biology Inc.

      Scopus rating (2018): CiteScore 3.92 SJR 2.403 SNIP 1.064

      Journal

    • Molecular and Cellular Endocrinology

      ISSNs: 0303-7207

      Elsevier Ireland Ltd

      Scopus rating (2018): CiteScore 3.62 SJR 1.362 SNIP 1.035

      Journal

    • Biochemical and Biophysical Research Communications

      ISSNs: 0006-291X

      Additional searchable ISSN (Electronic): 1090-2104

      Academic Press Inc.

      Scopus rating (2018): CiteScore 2.69 SJR 0.973 SNIP 0.706

      Journal

    • Journal of Leukocyte Biology

      ISSNs: 0741-5400

      FASEB

      Scopus rating (2018): CiteScore 3.69 SJR 1.929 SNIP 1.003

      Journal

    • Journal of Immunology

      ISSNs: 0022-1767

      Additional searchable ISSN (Electronic): 1550-6606

      American Association of Immunologists

      Scopus rating (2018): CiteScore 4.41 SJR 2.521 SNIP 1.04

      Journal

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