Natalie Chen, MD, PhD

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 ER stress, Unfolded Protein Response (UPR), immunology, cancer biology, biochemistry, transgenic and preclinical animal models. Our 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 (Nat Rev Cancer, 2021). Our study published in JCI revealed a critical role of the IRE1a/XBP1 branch of the UPR in mediating chemotherapy resistance and led to the first-in-human clinical trial of IRE1a RNase inhibitor. Our efforts in understanding proteostasis regulation revealed the direct cross-talk between oncogenic signaling and the protein quality control machinery and uncovered the mechanisms that account for the proteostasis rewiring in response to KRAS inhibition, allowing the drug-resistant cells to escape oncogenic KRAS addiction and gain resistance (Science, 2023). Another research area of the Chen laboratory focuses on ER Associated Degradation (ERAD). We recently discovered the crosstalk between ERAD complex and UPR in maintaining proteostasis and niche interactions (Nat Cell Biol, 2020, eLife, 2021).