Cancer immunotherapy can produce remarkable results, but many patients eventually stop responding because their immune cells become “exhausted.” These exhausted T cells lose their ability to attack tumors effectively, even after treatment with powerful therapies such as PD-1 checkpoint inhibitors. Scientists still do not fully understand why this exhausted state becomes so difficult to reverse.
Dr. Chen’s research combines cutting-edge imaging technology with cancer immunology to investigate the physical organization of DNA inside exhausted T cells. During his doctoral training at Princeton University, he built advanced microscopy systems capable of visualizing gene activity in living cells with extraordinary precision. More recently, he developed a powerful new imaging platform called GOLDFISH-X, which allows scientists to simultaneously study DNA structure, gene activity, and protein interactions within individual cells.
Using this technology, Dr. Chen will examine whether exhaustion-related genes become locked into stable three-dimensional DNA structures that prevent T cells from regaining normal function. He will identify the proteins that maintain these structures and test whether disrupting them can restore long-term T cell activity in tumors.
This work could reveal entirely new drug targets for improving immunotherapy. By identifying the molecular “anchors” that stabilize T cell exhaustion, Dr. Chen’s research may help scientists design combination therapies that allow more patients to achieve durable responses to cancer treatment.
Mentors
Taekjip Ha, PhD, Jared Rowe, PhD
Projects and Grants
Dissecting epigenetic maintenance in exhausted T cells by multimodal single-cell imaging and locus-proximal proteomics to identify targets for exhaustion reversal
