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Link to CV
Research Interests:
We study a line of knockout mice that are missing the pertussis
toxin sensitive G-protein alpha subunit, Giα2. These mice spontaneously
develop severe chronic inflammation of the colon at an early age.
Left unchecked, they go on to develop mucinous, non-polypoid adenocarcinomas
of the colon. Mice missing other Gi alpha subunits, including Giα1
and Giα3, do not become sick. Our overall goal is to understand
how changes in G-protein signaling affect other signaling pathways
in such a way as to effect the colitis and cancer phenotype.
In general, our ongoing studies involve 1) Determining how the loss of Giα2 in
different cellular compartments (epithelial, stromal, and hematopoietic) contribute
to the development of colitis and colon cancer, and 2) Identifying cancer-relevant
downstream signaling pathways whose activities are affected by the loss of Giα2.
Specifically, we have found that the loss of Giα2 leads to defects in mucosal
prostaglandin production which may contribute to the colitogenic phenotype. We
have also shown that Giα2-/- colonic epithelium is hyperproliferative and resistant
to apoptosis, and so we are trying to determine the mechanisms by which changes
in TGFβ and/or Wnt signaling may contribute to this phenotype.
Keywords:
Mucosal Immunology
Pertussis toxin-sensitive G-proteins
Arachidonic Acid and Prostaglandin Metabolism
Colitis - Associated Colon Cancer
Selected Publications:
Edwards, R.A., and Bryan, J. Fascins, a family of actin bundling
proteins. Cell Motil. Cytoskeleton.
32:1-9, 1995.
Dickason, R.R., Edwards R.A., Bryan, J., and Huston, D.P.
Versatile E. coli thioredoxin specific monoclonal antibodies afford convenient analysis and purification of prokaryote expressed soluble fusion protein. J. Immunol. Methods. 185:237-44,
1995.
Zhang, Y., Schlossman, S.F., Edwards, R.A., Ou, C.N., Gu, J., and Wu, M.X. Robotic impaired apoptosis, extended effector-phase of immune responses, and autoimmunity in IEX-1-Transgenic mice. Proc. Natl. Acad. Sci. U.S.A., 99:878-883, 2002.
Wu, J.Y., Zhang, Y., Edwards, R.A., Finegold, M.J., Jin, Y., and Wu, M.X.
Impairment of TGF-beta signaling in T cells of Giα2-/- mice. J. Immunol.
174(10):6122-6128, 2005.
Edwards, R.A., and Smock, A.Z. Defective arachidonate release and PGE2
production in Giα2-Deficient Intestinal and Colonic Subepithelial
Myofibroblasts. Inflammatory Bowel Diseases. 12(3):153-165, 2006.
Stiles, L.N., Hosking, M.P., Edwards, R.A., Strieter, R.M., and Lane,
T.E. Differential roles for CXCR3 in CD4+ and CD8+ T cell trafficking
following viral infection of the CNS. Eur J. Immunol. 36(3):613-22, 2006.
Hoang, B., Trinh, A., Birnbaumer, L. and Edwards, R.A. Decreased MAPK- and PGE2-dependent
IL-11 production in Giα2-/- colonic myofibroblasts. Am J Physiol Gastrointest
Liver Physiol. 292:G1511-G1519, 2007.
Edwards, R.A. Laser capture microdissection of mammalian tissue. J. Vis. Exp. (8):309, Epub 2007 Oct. 1.
Edwards, R.A., Wang, K., Davis, J.S. and Birnbaumer, L. A role for epithelial dysregulation in early onset colitis-associated colon cancer in GI2-alpha-/-mice. Inflamm. Bowel Dis. 14(7):898-907, 2008.
Tirotta, E., Fontaine, V., Picetti, R., Lombardi, M., Samad, T.A., Oulad-Abdelghani, M., Edwards, R.A., and Borrelli, E. Dopamine regulates D2 receptors presence at the plasma membrane by activation of sGia2. Cell Cycle. 14:2241-8
Chen, P-C., Kuraguchi, M., Velasquez, J., Wang, Y., Yang, K., Edwards, R.A., Gillen, D., Edelmann, W., Kucherlapati, R., and Lipkin, S.M. Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression. PLoS Genet. 13;4(6):e1000092, 2008.
Edwards, R.A., Witherspoon, M., Wang, K., Afrasiabli, K., Pham, T., Birnbaumer, L., and Lipkin, S.M. Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer. Cancer Research 2009, in press.
List
of Publications via PubMed (NIH National Library of Medicine)
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