The laboratory of Jin Chen, MD, PhD, is focused on characterizing the role of Eph receptor tyrosine kinases in tumor metabolism, cancer metastasis, neovascularization, and tumor immunity. Our approach involves a combination of mining human cancer datasets, CRISPR/Cas9 technology-enabled and traditional transgenic/ knockout animal tumor models, as well as conventional cell biology and biochemistry techniques. Eph RTKs and their ligands are dysregulated in tumor tissues and expression of these molecules is associated with tumor malignancy, resistant to therapy, and poor patient survival. 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 we are testing selective small molecule Eph receptor kinase inhibitors. We are also working on mTOR signaling downstream of multiple RTKs, including EphA2, in tumor and its microenvironment, with ultimate goal of developing mTORC2-specific inhibitors.