Research Interests

Our laboratory is interested in how cells interact with each other during tissue morphogenesis and remodeling. Cell-cell interactions are mediated by cell-cell adhesion and cytoskeletal proteins that coordinate cell movement during gastrulation or epithelial tube formation (see a movie of monolayer in motion). Aberrant loss of cell-cell adhesion leads to unrestricted cell movement that allows invasion into other tissues, a key step in progression of metastatic cancer. While cells in isolation have been extensively studied, their multi-cellular behavior still remains ambiguous. This is primarily due to the complexity of molecular interactions, signaling and cytoskeletal reorganization that results from cell-cell adhesion. Our focus is to understand molecular mechanisms of cell-cell adhesion and cytoskeletal organization that dictate the coordinate behavior of cells in tissues and organs.

Current research topics:

1. Assembly of cell-cell adhesion complexes

   To understand the molecular machineries that regulate the strength of cell-cell adhesion, one approach is to examine assembly of new cell-cell contacts where proteins are recruited to establish mature cell-cell adhesion. The adhesion strength is generated by reorganization of cell-cell adhesion and cytoskeletal proteins, however, molecular structure and signaling involved in the formation, maintenance or disassembly of cell-cell adhesion are not well understood. A quantitative relationship will be built on how the organization and dynamics of molecular complexes are related to mechanics and force generation by cytoskeletal networks during cell-cell contact formation.

   

2. Force generation mediated by cell-cell and cell-ECM adhesion

   Upon formation of cell-cell adhesion bonds, reorganization of cytoskeletal network generates forces that establish mature cell-cell contacts. We will directly measure forces generated by actin network using elastic substrates or artificial cadherin surfaces, and develop a molecular and mechanistic model of how cadherin-actin complexes generate force and withstand external strain.

3. Cell adhesion and motility in a three-dimensional matrix

   Two-dimensional tissue culture systems may be easier to study, but physiological processes in situ occur in three dimensions. This extra degree of freedom in space generates an entirely new cell morphology and structure. In suspension or collagen-matrix, kidney derived epithelial cells grow as a colony of spherical geometry called cysts. Using live-cell imaging, we will investigate formation of cell-cell adhesion and migration of cells within three-dimensional culture.

   

4. Computational analysis of adhesion and cytoskeletal dynamics

   Complex network of proteins interactions are often difficult to address experimentally. Cell-cell adhesion involves numerous proteins and signaling cascades that coordinate to regulate cell movement in tissues. We will use computational analysis to interpret, predict and design new experimental approaches.