Zheng Laboratory Research Interests
The research activities of Dr. Yi Zheng's laboratory focus on studies of the function and mechanism of regulation of the Rho family small GTP-binding proteins of Ras superfamily. The Rho GTPases are a class of intracellular signal transducers that play important roles in the regulation of diverse cellular activities including actin cytoskeleton reorganization, transcription activation, and DNA synthesis. Like Ras, mutation, overexpression or disruption of the normal mode of regulation of these GTP-binding and GTP-hydrolyzing molecular switches may lead to cellular transformation, morphological changes, and developmental disorders. By using a variety of current cellular, molecular, biochemical, and mouse genetic approaches, Dr. Zheng's lab attempts to understand the molecular mechanisms of signal transduction processes involving Rho GTPases, their regulators, and effector targets. The ultimate goals are to develop novel therapeutic reagents that may interfere with specific Rho pathways related to human pathological conditions.
The ongoing research projects include:
- Functional characterizations of the Dbl-family guanine nucleotide exchange factors (GEFs) of Rho GTPases. The goals are to understand the structure-function relationships of the conserved DH, PH, and other functional domains of the guanine nucelotide exchange factors, to dissect the upstream signaling pathways leading to the activation of specific Rho GTPases through the Dbl family GEFs, and to implicate the GEFs in tumorigenesis process using a mouse model system.
- Functional and mechanistic studies of the Rho GTPase-activating proteins (GAPs). The goals are to understand the functional interactions between the RhoGAP domains and Rho proteins and to determine the cellular functions and mode of regulation of these putative downregulators or effectors of Rho GTPases.
- Investigation of the functional interaction between Rho GTPases and p53 tumor suppressor pathway. The goals are to dissect the molecular pathways of Rho GTPases that cooperate with p53 deficiency in promoting cell transformation and invasion and to implicate individual members of the Rho family as anti-cancer targets in a mouse model.
- Development of small molecule inhibitors and other strategies that interfere with specific Rho protein functions. The goal is that the selected compounds could be explored as novel therapeutic reagents acting on specific Rho GTPase mediated signaling pathways that are associated with human diseases.
- Development of animal model systems by using transgenic and gene targeting methods in mice to study the physiological roles of Rho GTPases and their regulators. We are specifically focusing on the generation and/or characterization of RhoA, Cdc42 and Rac1 conditional knockout mice and the Cdc42GAP knockout mice.
Contact Us
For further information regarding the Cell Signaling program, please contact Dr. Yi Zheng at 513-636-0364. For additional information about the Division of Experimental Hematology, please contact Dr. David Williams at 513-636-0364. The Division of Experimental Hematology can be found in Room 6529 of Location R (Research Foundation Building).
