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Research Interests
Dysregulated intestinal beta-catenin signaling is associated with developmental abnormalities and colon cancer, a leading cause of morbidity and mortality. In Apcmin/+ mice, a commonly-used intestinal neoplasia model wherein Apc gene mutation results in increased nuclear translocation of beta-catenin, we observed that reduced expression and activation of type-3 muscarinic receptors (M3R) decreased both tumor number and size. Rac and Cdc42, small Rho family GTPases, regulate cytoskeletal reorganization, and cell invasion and migration. In colon cancer cells, increased Rac1 activation contributes to aberrant activation of canonical Wnt/β-catenin signaling. Our research objective is to identify and determine the role of betaPix,Cdc42/Rac-GEF, in the regulation of beta-catenin signaling unduced by MR activation in human colon cancer cells.Publications
A. Belo, K. Cheng, A. Chahdi, J. Shant, G. Xie, S. Khurana and J-P Raufman. Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion. American Journal of Physiology- Gastrointestinal and Liver Physiology. 300(5):G749-60, 2011.T.S. Pavlov, A. Chahdi, D.V. Vachugova, A. Vandewalle, O. Pochynyuk, A. Sorokin, and A. Staruschenko. Endothelin-1 inhibits the epithelial Na+ channel through betaPix/14-3-3/Nedd4-2. J. Am. Soc. Nephrol. 5:833-843, 2010.
A. Chahdi and A. Sorokin. The role of ï¢1Pix/caveolin-1 interaction in endothelin signaling through G ï¡ subunits. Biochem. Biophys. Res. Commun. 391:1330-1335, 2010
A. Chahdi and A. Sorokin. Endothelin-1 induces p66Shc activation through EGF receptor transactivation: Role of ï¢1Pix/Gï¡i3 interaction. Cell. Signal. 22:325-329, 2010
A. Chahdi and A. Sorokin. Endothelin-1 couples ï¢Pix to p66Shc: Role of ï¢Pix in cell proliferation through FOXO3a phosphorylation and p27kip1 down regulation independently of Akt. Mol. Biol. Cell. 19:2609-2619, 2008.
A. Chahdi and A. Sorokin. PKA-dependent phosphorylation modulates ï¢1Pix-GEF activity through 14-3-3ï¢ binding. Mol. Cell. Biol. 28:1679-1687, 2008.
A. Chahdi and A. Sorokin. Endothelin 1 stimulates ï¢1Pix-dependent activation of Cdc42 through the Gï¡s pathway. Exp. Biol. Med. 231: 761-765, 2006.
A. Chahdi, B. Miller and A. Sorokin. Endothelin 1 induces ï¢1Pix translocation and Cdc42 activation via protein kinase A-dependent pathway. J. Biol. Chem. 280: 578-584, 2005.
W.S. Choi, T. Hiragun, Y.M. Kim, H.P. Kim, A. Chahdi, E. Her, J.W. Han and M. A. Beaven. Activation of mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr. Mol. Cell. Biol. 24: 6980-6992, 2004.
A. Chahdi, A. Sorokin, M.J. Dunn and Y. Landry. The Rac/Cdc42 guanine nucleotide exchange factor ï¢1Pix enhances mastoparan-activated Gi-dependent pathway in mast cells. Biochem. Biophys. Res. Commun. 317: 384-9, 2004.
A. Chahdi, W.S. Choi, Y.M. Kim and M.A. Beaven. Mastoparan selectively activates phospholipase D2 in cell membranes. J. Biol. Chem. 278:12039-45, 2003.
A. Chahdi, W.S. Choi, Y.M. Kim and M.A. Beaven. Serine/threonine protein kinases synergistically regulate phospholipase D1 and 2 and secretion in RBL-2H3 mast cells. Mol. Immunol. 38: 1269-1276, 2002.
W.S. Choi, A. Chahdi, Y.M. Kim, P.F. Fraundorfer and M.A. Beaven. Regulation of phospholipase D and secretion in mast cells by protein kinase A and other protein kinases. Ann. N. Y. Acad. Sci. 968:198-212, 2002.
A. Chahdi, P.F. Fraundorfer and M.A. Beaven. Compound 48/80 activates mast cell phospholipase D via hetrotrimeric GTP-binding proteins. J. Pharmacol. Exp. Ther. 292: 122-130, 2000.
L. Daeffler, A. Chahdi, J.P. Gies and Y. Landry. Inhibition of GTPase activity of Gi proteins and decreased agonist affinity of M2 muscarinic acethylcholine receptors by spermine and methoctramine. Br. J. Pharmacol. 127: 1021-1029, 1999.
A. Chahdi, L. Daeffler, J.L. Bueb, J.P. Gies and Y. Landry. The M2 muscarinic receptor antagonist methoctramine activates mast cells via pertussis toxin-sensitive G proteins. Naunyn-Schmiedeberg's Arch. Pharmacol. 357: 357-362, 1998.
A. Chahdi, M. Mousli and Y. Landry. Substance P-related inhibitors of mast cell exocytosis act on G-proteins or on the cell surface. Eur. J. Pharmacol. 341: 329-335, 1998.
A. Chahdi, L. Daeffler, J.P.Gies and Y. Landry. Drugs interacting with G protein ï¡ subunit: selectivity and perspectives. Fundam. Clin. Pharmacol. 12: 121-132, 1998.
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