Xiaoyu (Ariel) Zhou, Ph.D.

Our lab leverages immune engineering and genome-editing technologies to develop next-generation immunotherapies. While recent advances—particularly CAR-T cell therapy—have revolutionized the treatment of blood cancers, long-term clinical data reveal that most patients relapse within a year, highlighting the need for more durable strategies.

Immune therapies, from checkpoint inhibitors (e.g., PD-1/CTLA-4) to CAR-T cells, depend critically on how immune and cancer cells communicate. Our recent work has explored how tuning the molecular dynamics of synthetic receptors (e.g., chimeric antigen receptors) can enhance T-cell function. For example, repurposing the endocytic properties of CTLA-4’s cytoplasmic tail was shown to improve CAR-T persistence and efficacy (Nature Immunology, 2023). Additionally, identifying specific and effective therapeutic targets remains a major bottleneck. To address this, we developed CRISPR knock-in mouse models enabling multiplexed and orthogonal gene editing at single-cell resolution. These tools provide a scalable platform to dissect genetic interactions and uncover novel targets. (Nature Biomedical Engineering, 2025).

Moving forward, by combining immunology, genome engineering, and computational approaches, the Zhou lab aims to:

• Decipher how synthetic receptors integrate with endogenous signaling networks, and whether their dynamics can be programmed to adapt to tumor heterogeneity.
• Develop high-throughput gene-editing systems to map how genetic perturbations alter cellular crosstalk and collectively shape immune function.