Basement membranes are thin extracellular matrices that form an interface between endothelial, epithelial, muscular, or neural cells and their adjacent stroma. Developmentally, basement membranes are the first extracellular matrix to appear. They are degraded and regenerated during development and wound repair. They not only support cells and cell layers, but they also have an essential role in tissue organization that affects cell adhesion, migration, proliferation, and differentiation. Additionally, basement membranes provide major barriers to invasion by metastatic tumor cells. Thickness and compositions of basement membranes are different in various tissues, suggesting tissue-specific functions. Thus, extracellular matrices have both functional and structural roles. The major molecules in basement membranes are collagen IV, laminin, perlecan, and nidogen/entactin. Recently, diversity has been discovered in the subunits that make up the trimers of collagen IV and laminin molecules. Our primary objectives have been to identify the specific functions of basement membrane components, to elucidate the mechanisms by which they are regulated, and to describe related protein interactions in development and diseases. Our effort has also focused on establishing animal models for basement membrane development and disease and on creating therapeutic reagents for diseases associated with basement membranes. We have also identified bioactive sites on laminin which have a number of activities such as promoting cell adhesion, migration, and neurite outgrowth, and affecting metastatic activity of tumor cells. These studies are aimed towards developing reagents useful for diagnostic and therapeutic applications.
Showing the most recent 10 out of 12 publications
