Matrix metalloproteinases (MMPs) can cleave components of the extracellular matrix. They are upregulated in most tumors and are believed to facilitate tumor growth and invasion. Accordingly, MMP inhibitors have been the targets of several clinical trials. Yet the use of MMP inhibitors as therapeutic agents has been problematic as they have caused unacceptable side effects. These side effects highlight the importance of understanding the normal physiological and developmental roles of MMPs. My laboratory is examining the requirements for MMPs in a model organism Drosophila melaogaster. Although vertebrates have more than 20 MMP family members, Drosophila has only two (non-redundant) MMPs; this organism is also highly amenable to developmental and physiological studies at the genetic and cell biological level. Our studies have demonstrated that MMPs are absolutely required for tissue remodeling events that normally occur during growth and during the transition from juvenile to adult forms.

My laboratory has an additional focus on wound healing. Normal wound healing shares many similarities with the tumor microenvironment, and indeed tumor invasion has been compared to “wound healing gone awry.” We are examining the contributions of blood cells and epithelia to healing normal epithelial wounds. In our model system, MMPs are required in both blood and in epithelia, as animals lacking MMPs in either tissue cannot heal puncture wounds. We seek to understand the functions of MMPs in this normal physiological process to use these findings to understand the tumor microenvironment.