Research

Our major focus has been to characterize the role of a new family of receptor tyrosine kinase (RTK), the Eph receptors and their ligands ephrins, in tumorigenesis and tumor angiogenesis. Our approach involves a combination of cell and molecular biology, biochemistry, transgenic and knock out animal models, and DNA microarray and proteomics technologies.

Eph RTKs and their ligands are elevated in tumor tissues and expression of these molecules is associated with degrees of tumor malignancy and poor prognosis in cancer patients. In particular, EphA2 receptor plays critical roles in both tumor cells and tumor blood vessels. Our laboratory demonstrated that epithelial EphA2 is required for cell proliferation and tumor initiation. We also showed that vascular endothelial EphA2 promotes tumor progression through angiogenesis. As EphA2 regulates both tumor cells and host microenvironment, it is a good target for cancer therapy. Several anti-EphA2 agents have been developed and some of those are under clinical trials. Current projects in the lab include: (1) Analysis of EphA2 functions in tumor resistance to EGFR/HER2 inhibitors; (2) Investigating the role of ephrin-A1 in mammary gland branching morphogenesis and breast cancer, using newly created ephrin-A1 knock out mice; (3) Dissecting the role of EphA2 receptor tyrosine kinase in tumor-endothelial interaction during metastasis; (4) Role of ephrins/EphAs in tumor cell-osteoclast/osteoblast interaction in breast cancer bone metastasis.