User:GarabetToby

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Background: B.Sc. in Biology (Haigazian University, Beirut, Lebanon). M.Sc. in Natural Products (Mediterranean Agronomic Institute of Chania, Crete, Greece) under the supervision of Antonios Makris. Ph.D. in Cell and Molecular Biology (University of Pennsylvania, Philadelphia); under the supervision of Erica A. Golemis, the thesis focused on the functional characterization of a novel RING finger-containing human gene, HEI10, and its role in the regulation of cell cycle progression.

Research Interest: I am interested in using chemical and genomic high throughput screening to identify regulators of cell growth control pathways. Specifically I study proteins that shuttle in and out of the nucleus. I utilize this mechanism as a readout to isolate regulators of such proteins. For instance, the adapter proteins 14-3-3 sigma bind to a variety of molecules and alter their subcellular localization and enzymatic activity. 14-3-3's localize to the cytoplasm at steady state, however they have been shown to translocate into and out of the nucleus. I have used a cell-based assay to screen a library of chemical compounds and have identified a number of small molecules that inhibit the export of 14-3-3 sigma from the nucleus. Similary, I have overexpressed a library of human kinases and isolate a number of proteins that interfere with the export of 14-3-3 sigma. Currently, I am focusing on understanding the biological role these small molecules and kinases play in the regulation of cellular growth via 14-3-3. In parallel, I am establishing a wider screen that uses shRNA plasmid-based libraries targeted to knockdown known human genes identified from the human genome project. These studies will elucidate a network of pathways that regulate nuclear export in general and 14-3-3 control. Finally, in collaboration with other people within the Silver group, we are using similar approaches to study other cellular processes such as RNA splicing (e.g. PTB and U2AF65) and mRNA nucleocytoplasmic translocation.

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