Dr. Chen’s investigations funded by NIH R01s are (1) tumor-blood vessel interaction, and (2) how tumor cell metabolism affects anti-tumor immunity. Her laboratory first pioneered work on the role of EphA2 receptor in tumor neovascularization and showed that endothelial-specific EphA2 also controls tumor growth by regulation of angiocrine factors through a circulation-independent mechanism. As mTOR kinase is a signaling node for multiple angiogenic factors, one of her current projects is to dissect the relative contribution of mTORC1 and mTORC2 in tumor blood vessels. Her team also discovered that EphA2 RTK promotes glutamine metabolism via the glutamine transporter ASCT2 and glutaminase GLS in a YAP and TAZ-dependent manner. Knockout GLS in tumor cells provides a favorable microenvironment for anti-tumor T cell recruitment and function.

The approach in the Chen laboratory 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.

Current projects in the lab include:

1. Glutamine metabolic competition between cancer cells and tumor infiltrating lymphocytes in breast cancer.
2. Regulation of fatty acid transendothelial transport by mTOR signaling in tumor blood vessel.
3. Targeting mTORC2 in squamous lung cancer and enhancing antitumor immunity.
4. SgRNA library screen for metabolic genes that regulate cancer metastasis and antitumor immunity.
5. EphA2 RTK in bone metastasis.