My laboratory studies how contextual signals are integrated by intracellular signaling pathways to orchestrate directed cell movement and thus tumor cell invasion. One important research area focuses on Mena, a molecule that regulates actin polymerization and cell:matrix/cell:cell adhesion. Changes in alternative splicing of the Mena mRNA during the epithelial-to-mesenchymal transition and during tumor progression produce distinct Mena protein isoforms with significantly different functions. In primary carcinomas, an epithelial-specific Mena isoform enhances cell:cell adhesion and suppresses invasion and metastasis. However, as tumors progress to malignancy another change alternative splicing produces an invasion-specific Mena isoform that promotes cell motility and chemotaxis, exerting a potent pro-metastatic effect on carcinoma cells. Fascinated by the divergent functions conferred to Mena by alternative splicing, we also are investigating the role of alternative splicing in metastatic progression.
Ludwig Center at MIT
77 Massachusetts Avenue, 76-158
Cambridge, Massachusetts, U.S. 02139
T 617 258 5159
F 617 258 5213