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个人简介
Research interests
The Sebti laboratory is focused on the mechanisms by which normal cells become cancerous with an emphasis on aberrant signal transduction pathways. Broadly the research areas of interests are related to signal transduction pathways from receptor tyrosine kinases to transcription factors. A major focus is on pathways regulated by the Ras family of GTPases. The work involves mechanistic studies of oncogenesis at the basic science level, validating cancer-causing proteins and pathways, developing chemical probes to target such pathways, and ultimately performing biomarker-driven clinical trials. Among our accomplishments are the discovery and development of inhibitors of aberrant signal transduction pathways such as inhibitors of STAT3, farnesyltransferase (FT), geranylgeranyltransferase-1 (GGT-1), Akt, RhoKinase, AuroraKinase, Proteasome, Bcl/Bax, Raf-1/Rb, Shp2, MDM2/p53 and others. Some of our findings including those with inhibitors of GGT-1 and Akt that have been translated from the laboratory to the clinic.
Currently, we are funded by a National Cancer Institute R35 Outstanding Investigator Award focusing on understanding the mechanism by which mutant KRas causes cancer. This is an exciting and highly integrated inter-disciplinary research projects concerning understanding aberrant oncogenic KRas signal transduction pathways in cancer and designing novel anti-cancer drugs based on this knowledge, with the following projects:
• Understanding how oncogenic K-Ras and Ral GTPase regulate the tumor suppressor p53.
• Identifying kinases that are synthetically lethal with mutant K-Ras.
• Identifying small molecules that bind K-Ras and inhibit its GTP activation, binding to its effectors and blocking oncogenesis.
• Identifying cell surface proteins specifically expressed on human cancers that harbor mutant K-Ras.
• Developing dual FT and GGT-1 inhibitors as novel anti-cancer drugs targeting human tumors that harbor mutant K-Ras.
研究兴趣
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Swamy R Adapa,Gregory A Hunter, Narmin E Amin, Christopher Marinescu, Andrew Borsky,Elizabeth M Sagatys,Said M Sebti,Gary W Reuther,Gloria C Ferreira,Rays Hy Jiang
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