Koh Cheng Gee
Telephone: 6316 2854
- Ph.D. - University of Cambridge, United Kingdom
- B.Sc.(Hons) - National University of Singapore
- Research Fellow, Institute of Molecular and Cell Biology, Singapore
- Investment Manager, Economic Development Board, Singapore
- Head, Biomedical Research Council, A*STAR, Singapore
- Research Associate, Institute of Molecular and Cell Biology, Singapore
The shape of a cell and its movement are critical to many fundamental biological processes. Differentiating neuronal cells send out neurites and axons and also migrate from the site of proliferation to other sites in response to developmental cues. Hematopoietic cells need to migrate through the blood vessels walls and tissue spaces to reach the site of infection. Metastatic cancer cells move and invade other tissues to cause the spread of the disease. The morphological changes required for cell movement involve modifying the actin cytoskeleton as well as actin-containing structures such as lamellipodia and filopodia that are also responsible for cell spreading and signal sensing.
The intracellular events promoting the alterations in the polymerisation status and localization of actin that are key to changes in cell morphology and motility are controlled by proteins that act as molecular switches. These switches relay signals from the external environment including the supporting matrix to elicit cellular responses by regulating various signalling networks. Some of the critical switches include the p21 Rho GTPases, a family of proteins that activate specific biochemical pathways.
Acting downstream of the Rho GTPases are effector proteins integral to pathways modulating the actin architecture. Work in my laboratory will focus on the effectors and regulators of these Rho GTPases. Of particular interest are kinases that are activated by the Rho GTPases and whose activities eventually lead to morphological changes. The kinases and their substrates are in turn regulated by phosphatases. One of the major kinases activated by the Rho GTPases is the p21-activated kinase (PAK), which plays an important role in growth factor signaling, inducing cytoskeletal reorganization that subsequently influences cell migration and metastasis functions. We have reported that PAK is dephosphorylated and downregulated by the phosphatase POPX. We are studying how these kinases and phosphatases regulate the signalling events that lead to the rearrangement of the actin structures required for cell morphology and motility.