The Sen Lab is a translational research program dedicated to intercepting cancer evolution and therapeutic resistance in thoracic malignancies. Its mission is to understand how lung cancers adapt under treatment, evade immune surveillance, and evolve, and to translate these insights into biomarker-guided therapeutic strategies. By integrating functional cancer biology, computational oncology, and clinical investigation, the lab identifies actionable vulnerabilities to prevent progression, overcome resistance, and improve patient outcomes.

In small-cell lung cancer, the lab focuses on DNA damage response vulnerabilities, including CHK1 and WEE1, and is expanding to targets such as ATR, ATM, and DNAPKcs to guide biomarker-driven clinical trials. The team also studies how DDR dysregulation and replication stress shape the immune microenvironment, demonstrating cGAS STING activation and synergy with immune checkpoint blockade. Complementary studies target epigenetic repression of antigen presentation, restoring MHC class I expression. Patient-derived models, multiomic profiling, and functional genomic screens drive these translational insights from bench to bedside.

In non-small cell lung cancer, the lab focuses on KRAS mutant tumors with STK11/KEAP1 co-mutations, uncovering metabolic rewiring, ferroptosis resistance, and novel therapeutic vulnerabilities. The lab is internationally recognized for leadership in lineage plasticity, defining how EGFR and ALK-driven tumors transform into neuroendocrine or small cell-like states under therapy. Using single-cell profiling, gene editing, and longitudinal clinical analyses, the Sen Lab identifies intrinsic and microenvironmental drivers of plasticity to prevent or reverse lineage switching and therapy resistance.