Xi Chen

The Chen laboratory studies how cancer and its immune microenvironment sense and respond to stresses and therapeutic insults to evade immune surveillance and develop drug resistance. We specialize in cancer stress biology, cancer immunology, therapy resistance, biochemistry, transgenic and preclinical animal models. We identified the ER stress signaling as a major mediator of chemotherapy resistance and immunosuppression in breast cancers (Cell, 2024; J Clin Invest, 2018, Nature Reviews Cancer, 2021), which led to the first-in-human clinical trial of IRE1α RNase inhibitor. Our efforts in understanding proteostasis regulation established how the proteostasis network is directly orchestrated by oncogenic drivers and how proteostasis bypasses oncogene addiction and is reprogrammed to promote therapy resistance to KRAS inhibitor (Science, 2023). Another research area of my laboratory focuses on stress responses in immunity and immune microenvironment. We discovered the crosstalk between the Unfolded Protein Response (UPR) and ER Associated Degradation (ERAD) in maintaining niche interaction (Nat Cell Biol, 2020) and T cell development (eLife, 2021) to regulate the immune system. These mechanism-driven highly translational research aims to elucidate the significance and mechanisms of stress responses in therapy resistance and anti-tumor immunity, and develop mechanism-based novel therapies to overcome therapy resistance and transform cancer to a manageable chronic disease.