Xingyu Chen

I am a physician-scientist whose primary disease focus is urologic oncology, especially bladder and urothelial cancers, with a broader research program spanning solid tumors and immune-cell therapy. I work at the intersection of clinical oncology, cancer genomics, tumor immunology, artificial intelligence, functional genomics, and single-cell & spatial systems biology.

My research starts from clinically meaningful problems encountered in oncology—why tumors recur, progress, evade immunity, or resist therapy—and connects patient cohorts with high-dimensional molecular profiling, computational modeling, functional perturbation, and mechanistic validation. Urologic cancers provide a central clinical framework for this work, while the underlying biological questions extend across cancer types.

A major focus of my work has been loss of the Y chromosome (LOY). In a co-first-author Nature study in 2023, we established a causal link between Y-chromosome loss in cancer cells, adaptive immune evasion, and response to immune-checkpoint blockade. In a first-author Nature study in 2025, I led pan-cancer analyses integrating more than one million single-cell profiles and clinical cohorts across 29 cancer types to reveal coordinated LOY across tumor and immune compartments and its impact on patient outcome.

My work also spans T-cell exhaustion and differentiation, AI-enabled radiogenomics, immunotherapy biomarkers, and current efforts in CAR-T systems biology and perturbational genomics. Across these projects, I aim to move from descriptive molecular associations toward causal mechanisms and actionable therapeutic hypotheses.