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• Investigation of the functional interaction between Rho GTPases, canonical/non-canonical self renewal pathway and the p53 tumor suppressor pathway, and determination of the role of Rho GTPase signaling in cancer stem cell regulation. The goals are to define the molecular mechanisms involving Rho GTPases that regulate Wnt/Notch signaling, cooperate with p53 deficiency and mediate EMT in promoting cell transformation and invasion and to implicate individual members of the Rho family as anti-cancer targets.
• Definition of the physiological role of Rho GTPases in hematopoietic stem cells, small intestinal stem cells, endothelial cells and liver cells, among other tissue/cell types, using conditional gene targeting approaches. We are specifically focusing on the characterization of RhoA/RhoC, Cdc42 and Rac1/Rac2 conditional knockout mice and the Cdc42GAP knockout mice.
• Rational design of small molecule inhibitors targeting the Rho GTPase signaling modules and application of such tools to establish the proof of principle that pharmacological targeting of Rho GTPase signaling is of therapeutic value in lung cancer, leukemia, aging, and stem cell modulation. The goal is to develop selected compounds, through in silica modeling and medicinal chemistry, for future therapeutic usage in human diseases.
• Revealing the physiological role of mTor and rictor/raptor signaling complex, well recognized targets of current pharmaceutics, in hematopoiesis/hematopoietic stem cell regulation and in small intestinal stem cell regulation, using mouse gene targeting approach.
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