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 cancer metastasis and tumor angiogenesis. Our approach involves a combination of oncogenomics and proteomics, confocal microscopy and imaging, transgenic and knock out animal models, and traditional cell biology and biochemistry techniques.
Eph RTKs and their ligands are dysregulated in tumor tissues and expression of these molecules is associated with clinical outcome of various cancer type. 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. Role of ephrin-A1, the ligand for EphA2 RTK, in tumor metabolism in breast cancer.
2. EphA2 in K-Ras and TKI-resistant EGFR mutant lung cancer and cancer stem cells.
3. Dissecting opposing roles of EphA2 and EphA3 in lung cancer.
4. Regulation of angiocrine signaling in tumor progression, metastasis, and stem cell function.