• Room 03.009 - Medical Biology Centre

    United Kingdom

Accepting PhD Students

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.

1990 …2017

Research output per year

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Personal profile

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).

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Projects

Research Output

The cytoplasmic tail of L-selectin interacts with the adaptor-protein complex AP-1 subunit mu1A via a novel basic binding motif

Dib, K., Tikhonova, I. G., Ivetic, A. & Schu, P., 21 Apr 2017, In : The Journal of biological chemistry. 292, 16, p. 6703-6714 12 p.

Research output: Contribution to journalArticle

Open Access
File
  • 5 Citations (Scopus)
    108 Downloads (Pure)

    Vasodilator-Stimulated Phosphoprotein (VASP)-dependent and -independent pathways regulate thrombin-induced activation of Rap1b in platelets

    Benz, P., Laban, H., Zink, J., Günther, L., Walter, U., Gambaryan, S. & Dib, K., 13 Sep 2016, In : Cell communication and signaling : CCS. 14, 21, 12 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 6 Citations (Scopus)
    194 Downloads (Pure)

    The histamine H4 receptor is a potent inhibitor of adhesion-dependent degranulation in human neutrophils

    Dib, K., Perecko, T., Jenei, V., McFarlane, C., Comer, D., Brown, V., Katebe, M., Scheithauer, T., Thurmond, R. L., Chazot, P. L. & Ennis, M., Sep 2014, In : Journal of Leukocyte Biology. 96, 3, p. 411-8 8 p.

    Research output: Contribution to journalArticle

  • 10 Citations (Scopus)

    Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury

    McAuley, D. F., O'Kane, C. M., Craig, T. R., Shyamsundar, M., Herwald, H. & Dib, K., 19 Jul 2013, In : BMC Pulmonary Medicine. 13, 6 p., 47.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 12 Citations (Scopus)
    120 Downloads (Pure)

    EFFECT OF HISTAMINE ON HUMAN NEUTROPHILS

    Ennis, M., Brown, V. & Dib, K., May 2011, In : Inflammation Research. 60, p. S335-S335 1 p.

    Research output: Contribution to journalArticle

    Prizes

    Tailoring the tail of L-selectin

    Karim Dib (Recipient), 01 May 2013

    Prize: Fellowship awarded competitively

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