Robert Wood Johnson Medical School
Dept. of Pathology & Laboratory Medicine
Piscataway, NJ 08854
Assembly, structure and function of basement membranes
Basement membranes are specialized cell-associated extracellular matrices whose molecular architectures are created through specific binding interactions of unique monomers. These matrices have suppor, perm-selective and cell regulatory functions. Both structure and function are altered in a number of diseases such as diabetes mellitus. Alports Syndrome, epidermolysis bullosa and some forms of congenital muscular dystrophy. The monomeric untis of basement membranes are, in themselves, large multi-domain glycoproteins and proteoglycans, each with several functions. Laminin and type IV collagen, for example, form polymeric networks as well as selectively bind and activate a number of different cellular receptors. Our fundamental research goals are to understand structure/function relationships in basement membranes at a molecular level of resolution, in particular: (a) the mechanisms of self-assembly and its regulation. the resulting molecular architectures. and how supramolecular organization contributes to function. (b) how structure and function become altered in diabetes, (c) the ole, and structural basis, of basement membranes. and their supramolecular assemblies, in the transmission of information to cells. These signals are mediated by beta-1, beta-3, and beta-4 class integrins, dystroglycan, and other cell-surface proteoglycans, and (d) the differential structural and cell-interactive information carried by the genetic variants of laminin and type IV collagen.