Andrea Page-McCaw
Assistant Professor
Education and Training
A.B. Harvard University
Ph.D. MIT
Postdoctoral UC Berkeley
Contact
E-mail: pagema@rpi.edu
Tel: (518) 276-4168
Office: Center for Biotechnology and Interdisciplinary Studies Rm. 2147
Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180
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.
Selected Publications
A. Page-McCaw. Remodeling the Model Organism: Matrix Metalloproteinase Functions in Invertebrates. (In press, Seminars in Cell and Developmental Biology).
A. Page-McCaw, A.J. Ewald, and Z. Werb. (2007). Matrix metalloproteinases and the genetic regulation of tissue remodeling. Nature Reviews Molecular Cell Biology 8, 221-233. (Cover article.)
M. Beaucher, E. Hersperger, A. Page-McCaw, A. Shearn. (2007). Metastatic ability of Drosophila tumors depends on MMP activity. Developmental Biology 303, 625-634.
S. Zhang, G.M. Dailey, E. Kwan, B.M. Glasheen, G.E. Sroga, A. Page- McCaw. (2006). An MMP Liberates the Ninjurin A Ectodomain to Signal a Loss of Cell Adhesion. Genes & Development 20, 1899-1910. (Featured in Science STKE, 5 July 2006.)
L. Myllykangas, J. Tyynela, A. Page-McCaw, G.M. Rubin, M.J. Haltia, M.B. Feany. (2005) Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. Neurobiology of Disease 19, 194-199.
A. Page-McCaw, J. Serano, J. M. Sante, G.M. Rubin (2003). Drosophila Matrix Metalloproteinases Are Required for Developmental Tissue Remodeling but Not Embryonic Development. Developmental Cell 4, 95-106.
