Staff Profile

General Profile Information
Staff Name Dr Karim Dib
Job Title Senior Lecturer
Location Medical Biology Centre Block 97 MBC Site
Room Number 03.009
School School of Medicine, Dentistry and Biomedical Sciences
Contact Details
Telephone +44 (0)28 9097 2634
I am a Member of the British Society for Immunology

I teach on the B.Med.Sci Immunology Module

Research Statement

GTP-binding proteins of the Ras superfamily (RhoA, Rac, Cdc42, Ras, Rap) are key intermediaries between cell surface receptors and effectors which regulate several cellular functions such as proliferation, differentiation and migration.  A hallmark of monomeric GTPases is their ability to dynamically cycle between a GDP-bound inactive to a GTP-bound active form.

I have initially focused my attention on the regulation of Rho GTPases (RhoA, Rac, Cdc42) by integrins in human polymorphonuclear neutrophils (PMN).  PMN represent an ideal model in which to study regulation of monomeric GTPases because most inflammatory functions of PMN are dependent on dynamic rearrangement of the actin-based cytoskeleton, a process which is well known to be regulated by Rho family GTPases. Their importance in the regulation of PMN functions is further emphasized by the fact that some monomeric GTPases such as Rac1 and Rac2 are part of the multi-component NADPH oxidase and thus play an important role in the regulation of the respiratory burst.  Thus, it is of great importance to elucidate the mechanisms by which integrins and pro-inflammatory cytokines regulate monomeric GTPases in human PMN to better understand how inflammatory functions of PMN are regulated during episodes of infection.

Recently, I also developed a research project aimed at understanding how e3B1, the human homologue of the Abi1 gene, couples growth factor receptors, such as EGFR, to activation of monomeric GTPases in fibroblasts.

Other Information

I am a regular referee for peer reviewed Journals (Journal of Immunology, Journal of Leukocyte Biology and Journal of Biological Chemistry).

I also am a regular referee for funding bodies (MRC, BBSRC and The Wellcome Trust)

TitleJournal NameYear
Exchange protein directly activated by cAMP 1 (Epac1) is expressed in human neutrophils and mediates cAMP-dependent activation of the monomeric GTPase Rap1 Journal of Leukocyte Biology Vol 90 (741-749)  DOI   2011
USP17 Regulates Ras Activation and Cell Proliferation by Blocking RCE1 Activity Journal of Biological Chemistry Vol 284 (9587-9595)  DOI   2009
Beta2 integrins target Rap GTPases to the plasma membrane by means of degranulation. Biochemical and Biophysical Research Communications Vol 376(4) (642-646)  DOI   2008
Nitric Oxide Produced in Response to Engagement of beta 2 Integrins on Human Neutrophils Activates the Monomeric GTPases Rap1 and Rap2 and Promotes Adhesion Journal of Biological Chemistry Vol 281(46) (35008-35020)  DOI   2006
E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor. Experimental Cell Research Vol 310(2) (463-473)  DOI 2005
Engagement of beta2 integrins recruits 14-3-3 proteins to c-Cbl in human neutrophils. Biochemical and Biophysical Research Communications Vol 317(4) (1000-1005)  DOI 2004
Fgr but not Syk tyrosine kinase is a target for beta2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils The Biochemical Journal Vol 370(2) (687-694)  DOI   2003
Down-regulation of Rac Activity during beta 2 Integrin-mediated Adhesion of Human Neutrophils Journal of Biological Chemistry Vol 278(26) (24181-24188)  DOI   2003
Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion. International journal of cancer. Journal international du cancer Vol 103(3) (344-351)  DOI 2003
Role of p190RhoGAP in beta2 Integrin Regulation of RhoA in Human Neutrophils Journal of Immunology Vol 166 (10) (6311-6322)    2001
Modification of adipocyte membrane adenylyl cyclase activity by NAD: evidence against NAD-induced endogenous ADP-ribosylation of Gsalpha protein. Biochemical and Biophysical Research Communications Vol 270(1) (203-208)  DOI 2000
BETA 2 integrin signaling in leukocytes. Frontiers in bioscience : a journal and virtual library Vol 5 (D438-D451)  2000
Cyclic AMP regulates G(omicronalpha) protein and mRNA levels by modulating the transcriptional rate of G(omicronalpha) gene. Molecular and Cellular Endocrinology Vol 156(1-2) (35-43)  1999
Cyclic AMP regulation of G(i alpha2) and G(i alpha3) mRNAs and proteins in astroglial cells. Journal of Neurochemistry Vol 71(6) (2271-2277)  1998
Impaired activation of phosphoinositide 3-kinase by insulin in fibroblasts from patients with severe insulin resistance and pseudoacromegaly. A disorder characterized by selective postreceptor insulin resistance. The Journal of clinical investigation Vol 101(5) (1111-1120)  DOI 1998
Expression of the putative inhibitor of the insulin receptor tyrosine kinase PC-1 in dermal fibroblasts from patients with syndromes of severe insulin resistance. Clinical Endocrinology Vol 47(1) (65-70)  1997
Sodium saccharin inhibits adenylyl cyclase activity in non-taste cells. Cellular Signalling Vol 9(6) (431-438)  1997
Two naturally occurring mutant insulin receptors phosphorylate insulin receptor substrate-1 (IRS-1) but fail to mediate the biological effects of insulin. Evidence that IRS-1 phosphorylation is not sufficient for normal insulin action. The Journal of biological chemistry Vol 271(12) (7134-7140)  1996
Effects of sodium saccharin diet on fat-cell lipolysis: evidence for increased function of the adenylyl cyclase catalyst. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity Vol 20(1) (15-20)  1996
12-O-tetradecanoyl-phorbol-13-acetate (TPA) counteracts the cAMP up-regulation of the expression of the stimulatory guanine nucleotide binding protein (Gs alpha) and Gs alpha messenger RNA in cultured pig thyroid cells. Molecular and Cellular Endocrinology Vol 99(2) (229-235)  1994
Cyclic AMP regulation of messenger RNA level of the stimulatory GTP-binding protein Gs alpha. Isoproterenol, forskolin and 8-bromoadenosine 3':5'-cyclic monophosphate increase the level of Gs alpha mRNA in cultured astroglial cells. European journal of biochemistry / FEBS Vol 219(1-2) (529-537)  1994
Modification of the amounts of G proteins and of the activity of adenylyl cyclase in human benign thyroid tumours. The Journal of endocrinology Vol 132(3) (477-485)  1992
The effect of glycosyl inositol-phosphate on cAMP production in isolated rat fat-cells is transduced by a pertussis toxin sensitive G-protein. FEBS Letters Vol 286(1-2) (105-109)  1991
Alteration of the functional activity of Gs protein in thyrotropin-desensitized pig thyroid cells. Molecular and Cellular Endocrinology Vol 75(2) (123-131)  1991
Cyclic AMP regulation of Gs protein. Thyrotropin and forskolin increase the quantity of stimulatory guanine nucleotide-binding proteins in cultured thyroid follicles. The Journal of biological chemistry Vol 265(32) (19942-19946)  1990