Office Phone: 318-675-5668
Laboratory Phone: 318-675-5188
Office Fax: 318-675-5180
B.S., 1979, Bar Ilan University, Israel
Ph.D., 1985, State University of New York at Albany
Altered protein synthesis in solid tumors; gene expression; radioresistance by the protein kinase Tousled; gene therapy
Dr. De Benedetti's major research interests include understanding the regulation and functions of the protein synthesis initiation factor eIF4E (cap-binding protein), altered protein synthesis in solid tumors, and radioresistance conferred by the protein kinase Tousled.
The protein synthesis initiation factor eIF4E can transform cells in tissue culture. Moreover, eIF4E is overexpressed in a variety of solid tumors. The potential clinical implications are being investigated. The principal goals of our work include: 1) to establish the importance of dysregulation of protein synthesis in cancer etiology; 2) to determine the chain of events and the components which, in response to increased eIF4E activity, mediate these alterations in growth regulation, proliferation, and differentiation; 3) to identify critical oncogene transcripts upregulated by eIF4E; 4) to look for possible strategies to eradicate prostate and breast metastases taking advantage of the high expression of eIF4E in cancer cells to selectively express a suicide gene; and 5) to utilize a cDNA library we have constructed of mRNAs that require elevated eIF4E for translation. We then plan to use this library for the identification of novel potential oncogenes. From this library we have recently cloned the mRNA for a translationally regulated protein kinase called Tousled. We found that Tousled is involved in aspects of chromatin remodeling during repair of DNA damage and confers a high degree of resistance to radiation when overexpressed. This resistance occurs via its interaction with the chromatin assembly factor Asf1 that remodels chromatin during repair and via its interaction with the radiation repair protein Rad9. We have recently identified chemical inhibitors and activators of TLK1B, and are using them as potential radio- chemo-sensitizers, as well as probes to dissect the molecular activities of these kinases.
All Publications: PubMed