Position

Assistant Professor

University Education

1999-2001    FRSQ Postdoctoral fellow, University of Western Ontario
1995-1998    Ph.D. (Pharmacology), University of Montreal
1990-1994    M.Sc. (Pharmacology), Al-Arab Medical University, Libya
1985-1990    B.Sc (Pharmacy), Al-Fateh Medical University, Libya

Research Interests

Research in our lab is focused on two specific areas:

1. Understanding (i) how the inflammatory reaction modulates the AHR-regulated genes, and (ii) the role of coregulatory (coactivator and corepressor) proteins and the interaction between inflammation and the AHR in the regulation of AHR-regulated genes. These studies will a) increase our knowledge about the regulation of the AHR-regulated genes during inflammation and shall detail the signaling pathways and mechanisms underlying the modulation of the AHR-regulated genes, and b) provide information that will make drug usage safer by decreasing the incidence of adverse effects. This will help to diminish health care costs, as well as to design strategies that improve treatment of inflammation-dependent illnesses and disorders.

2. Understanding (i) the potential interaction between heavy metals and AHR ligands which are common in the environment on the regulation of AHR-regulated genes, and (ii) investigate the effects of AHR ligand/metal mixtures on AHR ligands-mediated mutagenicity and carcinogenicity. These studies will a) increase our knowledge about the effect of heavy metals on the AHR-regulated genes, and b) provide the information that will help to design strategies to improve treatment of AHR ligands mediated mutagenicity and carcinogenicity.

AHR signaling pathways. In the absence of a ligand, AHR is found bound to the chaperone protein HSP90 in the cytoplasm. Upon ligand binding, the HSP90 is displaced from the AHR, which now enters the nucleus and complexes with ARNT. The heterodimer then binds to its response elements (xenobiotic response element) to alters expression of a number of genes including; CYP1A1, CYP1A2, CYP1B1, NAD(P)H quinone oxidoreductase, glutathione S-transferase Ya subunit, aldehyde dehydrogenase-3 and UDP-glucuronosyltransferase 1A6. In addition, ARNT forms a heterodimer with hypoxia inducible factor-1a (HIF-1a) to regulate hypoxia-inducible genes (Whitlock, J.P., Jr. Annu. Rev. Pharmacol. Toxicol. 39:103-125, 1999).

Link to our lab home page [click here]

Selected Publications:

1. Seubert, J.M., Darmon, A., El-Kadi, A.O.S., D’Souza, S., Bend, J.R. Apoptosis in murine Hepa 1c1c7 WT, C12 and C4 cells mediated by bilirubin. Molecular Pharmacology 62:257-264, 2002.  [Abstract]
2. Barakat, M., El-kadi, A.O.S., du Souich P. L-NAME prevents in vivo the inactivation but not the down-regulation of hepatic cytochrome P450 caused by an acute inflammatory reaction. Life Sciences, 69:1559-1571, 2001. [Abstract]
3. Bleau, A-M., Fradette, C., El-Kadi, A.O.S., Côté, M-C., du Souich, P. Cytochrome P450 down-regulation by serum from humans with a viral infection and from rabbits with an inflammatory reaction. Drug Metabolism and Disposition, 29:1007-1012, 2001. [Abstract]
4. El-Kadi, A.O.S., Bleau A.M., Dumont, I., Maurice, H., du Souich, P. Role of reactive oxygen intermediates in the decrease of hepatic cytochrome P450 activity by serum of humans and rabbits with an acute inflammatory reaction. Drug Metabolism and Disposition, 28:1112-20, 2000.  [Abstract]
5. Kurdi, J., Maurice, H., El-Kadi, A.O.S., Ong, H., Kobusch, A.B., Dalkara, S., Belanger, P.M., du Souich, P. Effect of hypoxia alone or combined with inflammation and 3-methylcholanthrene on hepatic cytochrome P450 in conscious rabbits. British Journal of Pharmacology, 128:365-373, 1999. [Abstract]
6. Serrar, H., El-Kadi, A.O.S., du Souich, P., Haddad, P. Cytochrome P-450 content and activity after cold storage of rat hepatocytes in University of Wisconsin and sodium-lactobionate-sucrose solutions. Liver Transplantation, 5:1-7, 1999.[Abstract]
7. El-Kadi, A.O.S., du Souich, P. Depression of the hepatic cytochrome P450 by an acute inflammatory reaction: characterization of mediators in human and animal serum and in the liver. Life Sciences, 63:1361-1370, 1998. [Abstract]
8. El-kadi, A.O.S, Maurice, H., Ong, H., du Souich, P. Down-regulation of the hepatic cytochrome P450 by an acute inflammatory reaction: implication of mediators in human and animal serum and in the liver. British Journal of Pharmacology, 121:1164-1170, 1997. [Abstract]
9. Barakat, M., El-kadi, A.O.S., du Souich P. In vivo and ex vivo and in vitro effect of l-arginine and l-NAME on the metabolism of theophylline in the rabbit. Drug Metabolism and Disposition, 25:191-195, 1997. [Abstract]