Office Address:
1161 21st Avenue South, Medical Center North, Room / Suite T-3113, Nashville, TN 37232-2681

Professor of Medicine, Division of Rheumatology & Immunology

Research Description

Our major focus has been to characterize 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.

Current projects in the lab include:

1. EphA2 RTK in tumor metabolism and stem cell function in breast cancer.

2. Role of EphA2 in tumor immunity in K-Ras and TKI-resistant EGFR mutant lung cancer.

3. Endothelial mTORC1 and mTORC2 in tumor progression, metastasis, and angiocrine signaling.

4. Targeting mTORC2 in cancer subtypes bearing Rictor-amplification, PI3KCA mutation, or PTEN-deletion.

5. Developing mTORC2-specific inhibitors.