Projects per year
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).
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Collaborations and top research areas from the last five years
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R1778CEM: To evaluate the role of the histamine four recpetor in the clearance of lung pathogens
Dib, K. (PI) & Valvano, M. A. (CoI)
26/05/2017 → 31/12/2020
Project: Research
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R1636CEM: MRC P2D 2015 - Feasibility studies using H4Rantagonists - development of a collaboration with a Clinical Stage Biotech Company
Dib, K. (PI)
06/06/2016 → 30/11/2016
Project: Research
Research output
- 33 Article
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Histamine produced by gram-negative bacteria impairs neutrophil's antimicrobial response by engaging the histamine 2 receptor
Dib, K., El Banna, A., Radulescu, C., Lopez Campos, G., Sheehan, G. & Kavanagh, K., 2023, In: Journal of innate immunity. 15, 1, p. 153–173 21 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile5 Citations (Scopus)104 Downloads (Pure) -
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 journal › Article › peer-review
Open AccessFile7 Citations (Scopus)201 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 Sept 2016, (Early online date) In: Cell communication and signaling : CCS. 14, 21, 12 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile29 Citations (Scopus)495 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., Sept 2014, In: Journal of Leukocyte Biology. 96, 3, p. 411-8 8 p.Research output: Contribution to journal › Article › peer-review
19 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 journal › Article › peer-review
Open AccessFile18 Citations (Scopus)234 Downloads (Pure)
Prizes
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Tailoring the tail of L-selectin
Dib, K. (Recipient), 01 May 2013
Prize: Fellowship awarded competitively
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