Assistant Professor, Department of Biology
Rensselaer Polytechnic Institute

Education:
Ph.D., Biology, Massachusetts Institute of Technology, 1998
A.B., History and Science, Magna Cum Laude, Harvard University, 1989

Career Highlights:
Page-McCaw is among the biology faculty’s newest members, having joined in 2004 after a six-year research fellowship at the University of California, Berkeley. While in graduate school at MIT, she conducted research at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

Professional meetings to which she has lectured include the 2004 Gordon Research Conference on Proteolytic Enzymes and Their Inhibitors, the 43rd Annual Drosophila Research Conference, San Diego, Calif., 2002; and the European Molecular Biology Organization (EMBO) Workshop on Meiotic Maturation, Cuenca, Spain, 1997.

She has received many academic honors, including a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research, and a National Science Foundation Pre-doctoral Fellowship. Harvard also recognized Page-McCaw for her thesis.

Research Areas:
In order for cells to function together in tissues or organs, cells must communicate with each other. This is known as cell-cell signaling. Many cell-cell signaling pathways have been identified, and in their simplest form, these signaling pathways consist of an extracellular signal, a transmembrane receptor, and intracellular signaling components that carry the information from the receptor to the inside of the cell. The cellular response to a signal is a change in behavior, such as cell division or differentiation. Cell signaling pathways are important for normal functions such as development and the immune response among other phenomena. However, inappropriate cell signaling can lead to cancer.

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 an 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 display defects in their tracheae, and it appears that these defects stem from an inabiltiy of the tracheal cells to separate from the cuticle at molts. 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 adhesion 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.

This basic research is expected to be medically relevant. Both Mmp1 and Ninjurin A are highly conserved between flies and humans, and the vertebrate homologs have medical significance: the MMP family of extracellular proteases is highly implicated in cancer and inflammatory diseases; and the Ninjurin family of transmembrane proteins was identified by their expression in regenerating nerves. Thus we hope our work will give insights into cancer and nerve regeneration.

Selected Publications:
S. Zhang, G.M. Dailey, E. Kwan, B.M. Glasheen, G.E. Sroga, and A. Page-McCaw. (2006). An MMP Liberates the Ninjurin A Ectodomain to Signal a Loss of Cell Adhesion. Genes & Development 20, 1899-1910.

A. Page-McCaw, J. Serano, J.M. Sante, and G.M. Rubin, “Drosophila Matrix Metalloproteinases are Required for Developmental Tissue Remodeling, But Not Embryonic Development,” Developmental Cell, 4, (1), 95-106, (2003).

D.P. Moore,* A.W. Page,* T.T. Tang, A.W. Kerrebrock, and T.L. Orr-Weaver, “The Cohesion Protein MEI-S332 Localizes to Condensed Meiotic and Mitotic Centromeres Until Sister Chromatids Separate,” Journal of Cell Biology, 140, (5), 1003-1012, (1998).

A.W. Page and T.L. Orr-Weaver, “Activation of the Meiotic Divisions in Drosophila Oocytes,” Developmental Biology, 183, (2), 195-207, (1997).

L.K. Elfring, J.M. Axton, D.D. Fenger, A.W. Page, J.L. Carminati, and T.L. Orr-Weaver, “The Drosophila PLUTONIUM Protein is a Specialized Cell Cycle Regulator Required at the Onset of Embryogenesis,” Molecular Biology of the Cell, 8, (4), 583-593, (1997).

A.W. Page and T.L. Orr-Weaver, “Stopping and Starting the Meiotic Cell Cycle,” Current Opinion in Genes and Development, 7, (1), 23-31, (1997).

L. Frostesjo, I. Holm, B. Grahn, A.W. Page, T.H. Bestor, and O. Heby, “Interference with DNA Methyltransferase Activity and Genome Methylation During F9 Teratocarcinoma Stem Cell Differentiation Induced by Polyamine Depletion,” Journal of Biological Chemistry, 272, (7), 4359-4366, (1997).

A.W. Page and T.L. Orr-Weaver, “The Drosophila Genes Grauzone and Cortex are Necessary for Proper Female Meiosis,” Journal of Cell Science, 109, (7), 1707-1715, (1996).

H. Leonhardt,* A.W. Page,* H.-U. Weier, and T.H. Bestor, “A Targeting Sequence Directs DNA Methyltransferase to Sites of DNA Replication in Mammalian Nuclei,” Cell, 71, 865-873, (1992).

L.L. Carlson, A.W. Page, and T.H. Bestor, “Properties and Localization of DNA Methyltransferase in Preimplantation Mouse Embryos: Implications for Genomic Imprinting,” Genes and Development, 6, 2536-2541, (1992).

A. Czank, R. Hauselmann, A.W. Page, H. Leonhardt, T.H. Bestor, W. Schaffner, and M. Hergersberg, “Expression in Mammalian Cells of a Cloned Gene Encoding Murine DNA Methyltransferase,” Gene, 109, 259-263, (1991).

*Indicates equal contribution by first two authors

Contact Information:
Andrea Page-McCaw
(518) 276-6446
pagema@rpi.edu
http://j2ee.rpi.edu/biology/update.do?artcenterkey=3