Department of Oncology
Lombardi Comprehensive Cancer Center
E301 Research Building
3970 Reservoir Rd NW
Washington, DC 20057-1469
Our research encompasses basic cell biology of tumor cell invasion, focusing on two tyrosine kinases, c-Src and Syk, with opposing roles in cancer metastasis. A major focus is invadopodia, the cell surface membrane protrusions formed during tumor cell invasion, and their role in invasion and metastasis. We use cortactin, a Src substrate, and MT1-MMP, an extracellular matrix-degrading, membrane protein, to identify and study the formation of invadopodia and acquisition of proteolytic activity. High resolution light and electron microscopy techniques are used to identify these structures and examine the membrane-associated signal transduction events that occur in conjunction with the formation of invadopodia. In vitro and in vivo assays are used to measure the consequent matrix adhesion, proteolysis and phagocytosis that are mediated by invadopodia. We also focus on determining the mechanism of breast cancer tumor suppression by the Syk tyrosine kinase. Utilizing mouse model systems, 3D culture and normal breast epithelial cell or tumor cell lines in vitro, we seek to determine the contribution of Syk to pre-malignant progression as well as its role in tissue conversion to the invasive and malignant phenotype.