Andrea Page-McCaw
On July 1 this year Associate Professor Andrea Page–McCaw will join us. Andrea studies protease-mediated cell signaling and tissue remodeling in Drosophila, and comes to us from the Rensselaer Polytechnic Institute in NY. Andrea’s lab and office will be located in 4124 MRB III.
Research Interests
Protease-mediated cell-cell signaling and tissue remodeling in Drosophila
During embryogenesis, animals develop complex structures, but they often have to modify these structures to meet the demands of continuing growth or environmental challenge. This is known as tissue remodeling. The matrix metalloproteinase (MMP) family of extracellular proteases is required for tissue remodeling events throughout the animal kingdom. These proteases are also upregulated in cancer and many inflammatory conditions such as arthritis. Understanding how MMPs promote tissue remodeling, both in normal and pathological circumstances, is a central question in my laboratory. One of the ways that MMPs promote remodeling is through the generation signaling molecules that travel between cells to transmit information that modifies cell behavior.
Drosophila melanogaster (the common fruitfly) has been an important model organism for understanding how signaling pathways regulate cell behaviors because of their advanced genetics and beautiful cytology. In contrast, cultured cells have been very useful for working out the details of signaling pathways because they are simple and easily manipulated. Using both cultured cells and whole fruitflies, our laboratory has recently identified a new signaling pathway that governs cell adhesion. In cultured cells, this pathway controls whether the cells adhere to a substrate. Experiments from insect S2 cell culture have shown that a transmembrane protein (Ninjurin A) is cleaved by the MMP extracellular protease (Mmp1). This cleavage liberates an ectodomain (or extracellular domain) of Ninjurin A that acts as a signaling molecule. Cells that are exposed to this signaling molecule lose adhesion and can float away.
In vivo, we believe this pathway is important in regulating whether cells adhere to an extracellular matrix in the tubes that make up the Drosophila tracheal (breathing) system. Tracheal tubes are made up of epithelial cells, and the tubes are lined at the apical surface with an apical extracellular matrix called cuticle. Mutants in the Mmp1 extracellular protease cannot remodel their tracheal tubes to elongate as the animal grows. We have found that the Mmp1 protease and the Ninjurin A transmembrane protein are both expressed in the tracheal tubes. We are currently investigating how Mmp1 and Ninjurin A cooperate to regulate tracheal cell behavior in vivo. Our longer term goal is to understand the molecular components of the Ninjurin A/ Mmp1 signaling pathway and to understand how they function in vivo using the tools of genetics, biochemistry, and cell biology. My laboratory is funded by grants from the National Institutes of Heatlth (NIGMS) and the March of Dimes.