Kat Mueller, PhD, Postdoctoral Fellow Children's Hospital of Philadelphia Area of Research: All Cancers Kat Mueller, PhD, is investigating the molecular mechanisms that determine CAR T-cell persistence—why some engineered immune cells continue fighting cancer for years, while others lose effectiveness or die off soon after treatment. CAR T-cells, often described as “living drugs,” have transformed cancer therapy, but not all patients experience lasting responses. By identifying key factors that govern CAR T-cell survival, Dr. Mueller’s research aims to enhance the durability and effectiveness of this breakthrough treatment. Dr. Mueller’s work centers on FOXO1, a transcription factor that plays a critical role in programming CAR T-cells for long-term function. Using CRISPR-based gene editing and advanced sequencing techniques, she has shown that FOXO1 helps CAR T-cells resist exhaustion and maintain memory-like properties that contribute to their persistence. To further understand this mechanism, she is analyzing CAR T-cells from pediatric clinical trials—comparing those from patients in remission for up to ten years with those from patients who relapsed within six months. Her goal is to uncover how FOXO1 and related gene networks shape CAR T-cell fate. “By unlocking the molecular programming behind CAR T-cell persistence, we can design next-generation therapies that give more patients durable, long-term remission,” says Dr. Mueller. “Transcription factor engineering offers an exciting new frontier to fine-tune CAR T-cells for lasting effectiveness.” With a background in bioengineering, Dr. Mueller has led innovative research on nonviral CAR-T manufacturing, metabolic profiling of engineered T cells, and transcriptional regulation of CAR-T memory. Her work has resulted in multiple high-impact publications, including a recent study in Nature demonstrating how FOXO1 overexpression enhances CAR-T persistence and tumor control. By bridging fundamental immunology with translational applications, Dr. Mueller’s research is paving the way for more effective and resilient CAR T-cell therapies. Projects and Grants Identifying Molecular Determinants of CAR T-cell Persistence Children’s Hospital of Philadelphia | All Cancers | 2025 | Evan Weber, PhD
