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437 Clinical
Research Building |
Research interests are in the area of tumor suppressor genes, transcription factors, drug resistance in cancer and novel cancer therapies including TRAIL and mutant p53 modifying drugs. The major effort in the lab involves efforts to understand the role of the p53 tumor suppressor and its transcriptional target genes in chemo- and radio-sensitivity. There is an interest in molecular in vivo imaging of gene expression and high throughput applications for drug discovery. One area of focus has involved the biochemical purification of p53 protein from drug-treated cells and the identification of modifications by mass-spec analysis. We are attempting to characterize a novel mechanism of p53 wild-type conformational stabilization that has implications for cancer therapy. Another area of focus has involved the identification and characterization of cell cycle dependent changes in the phosphorylation and function of the p21WAF1 cell cycle inhibitor. Other ongoing areas of relevance include chromatin immunoprecipitation and characterization of protein interactions that can influence the selectivity of p53 under different circumstances, and the characterization of a novel family of caspase-specific ubiquitin ligases that may regulate cell death though proteolysis or sub-cellular trafficking. Selected Publications: Fei, P., Bernhard, E.J., and El-Deiry, W.S. (2002) Tissue-specific induction of p53 targets in vivo. Cancer Res. (in press). Sax, J.K., Fei, P., Murphy, M.E., Bernhard, E.J., Korsmeyer, S.J., and El-Deiry, W.S. (2002) BID transcriptional regulation by p53 contributes to chemosensitivity. Nature Cell Biology 4:842-849. MacLachlan, T.K., and El-Deiry, W.S. (2002) Apoptotic threshold is lowered by p53 activation of caspase 6. Proc. Natl. Acad. Sci. USA 99:9492-9497. MacLachlan, T.K., Takimoto,
R. and El-Deiry, W.S. (2002) BRCA1 directs a selective p53-dependent transcriptional
response towards growth arrest and DNA repair targets. Mol. Cell. Biol.
22:4280-4292. Burns, T.F. and El-Deiry, W.S. (2001) Identification of Inhibitors of TRAIL-Induced Death (ITIDs) in the TRAIL sensitive colon carcinoma cell line, SW480, using a genetic approach. J. Biol. Chem. 276:37879-37886. |
