Our laboratory is focused on the role of small GTPases in regulating animal cell motility and actin cytoskeleton.
Regulation of cell migration is essential for mammalian development, immune response, and wound healing. De-regulation of cell migration and adhesion leads to human diseases such as cancer invasion and metastasis. We are studying the role small GTPases on the control of cell migration.
Binding of chemotactic factors to plasma membrane receptors initiates intra-cellular signal transduction and elicits cell migration. Rho family small GTPases are principal regulators of cell migration. We are studying how rho GTPases control cell migration and adhesion.
We are studying the mechanism of cell migration in three-dimensional environments. Historically, cell biologists are studying cells moving on coverslips in tsuues culture dishes. On the coverslips, cells extend lamellae and crawls on the substrates. However, inside our bodies, cells move in connective tissues surrounded by extracellular matrixes. This enivironment is three-dimensional (3D) and quite different from moving on tissue culture dishes. We are studying how immune cells and cancer cells move in 3D environments.
Epithelial cells connect each other and make sheets. The cell-cell adhesion is dynamically regulated through Cadherin family adhesion molecules and the cell-cell adhesion is de-regulated when the cells become cancerous. The epithelial cell adhesion is controlled by actin cytoskeleton. We are studying how Rho GTPases regulate epithelial cell adhesion.
When epithelial cells are cultured in 3D matri-gel environment, cells grow and become 3D structure called cyst. Cells protrude from cysts and produce tubular structures when the cysts are stimulated by scattering factors. We are studying how Rho GTPases are involved in the building of epithelial 3D structures.
When carcinoma cells become malignant, they lose connection from surrounding neighbor cells and detach from the epithelial sheet. Then, cancer cells break basement membrane and penetrate into connective tissues. The malignant cancer cells move inside connective tissues and migrate into blood vessels and metastasize. Toe understand the mechanism of malignant transformation, our laboratory is focused on the mechanism of cell-detachement and cancer cell migration in 3D environment.
Differentiated podocytes are specialized epithelial cells that possess actin-rich projections known as foot processes to cover the glomerular capillary loops. Under pathological conditions, podocytes manifest foot process effacement characterized by a flattening of the processes with disruption of the cell-cell adhesion. Formation and maintenance of foot process are dependent on actin cytoskeleton. Moreover, podocytes need to adhere to basement membrane and withstand high pressure in the capillaries. Thus, podocyte’s actin cytoskeleton is critically involved in podocyte functions. Rho GTPases are master regulators of actin cytoskeletal dynamics and maintenance of actin stress fibers and induction of motility of podocytes are dependent on activation and inactivation of Rho GTPases. We are studying how structure and function are regulated by Rho GTPases.