The Chen laboratory studies the molecular and biological processes governing the development of brain malignancies, including primary (e.g., glioblastoma) and metastatic (tumors originating from other locations in the body, such as breast cancer) brain cancers. Specifically, the laboratory focuses on characterizing the molecular mechanisms governing the symbiotic interactions between cancer cells and immune cells (including macrophages, microglia, myeloid-derived suppressor cells and T cells) in brain malignancies, and how such heterotypic signaling enables a tumor-promoting ecosystem and informs therapeutic strategies intercepting these co-dependencies.
The laboratory takes an integrated strategy combining gain- and loss-of-function approaches, in vitro and in vivo systems, as well as proteomic and transcriptomic analyses to:
(1) study how genetic (e.g., PTEN mutation and deletion) and epigenetic (e.g., CLOCK regulation) alternations of cancer cells and/or cancer stem cells can shape an immunosuppressive tumor microenvironment by regulating the infiltration and polarization of myeloid cells (i.e., macrophages, microglia, and myeloid-derived suppressor cells);
(2) elucidate the mechanisms for how these infiltrated and polarized myeloid cells affect tumor growth, brain metastasis, and anti-tumor immunity (e.g., T cell biology);
(3) understand how this tumor-immune cell symbiosis affects the effectiveness of cancer therapies (e.g., immunotherapy, anti-angiogenic therapy, and conventional therapies), thus developing novel and effective combination therapies.
Our mission is to uncover novel mechanisms governing the development and progression of brain malignancies (including primary and metastatic brain cancers) and offer new therapeutic strategies for patients with these diseases.