Federal Grant Award Summary

The University of Southern California received a $456,500 Project Grant from the National Institute of General Medical Sciences under the Biomedical Research and Research Training program (CFDA 93.859), awarded February 15, 2026, with completion targeted for December 31, 2030. This five-year research initiative investigates the mechanism and function of XIST, a long non-coding RNA essential to X chromosome inactivation (XCI) maintenance—a fundamental epigenetic process that equalizes X-linked gene expression between females and males. The research builds on preliminary findings that XIST plays an unexpected role in maintaining X-inactivation by preventing the escape of immune-associated genes from silencing in somatic B cells, a process previously thought to operate independently of XIST.

The deliverables include comprehensive research findings addressing three core scientific questions: how XIST functional domains coordinate to maintain X-inactivation, how cellular signaling pathways influence XCI maintenance fidelity, and when and where XIST is required for XCI maintenance throughout the lifespan. The research employs advanced methodologies including CRISPR perturbation, allele-specific chromatin profiling, RNA-mediated proteomics, single-cell genomics, and mouse models with clonal XCI tracking capability. Upon completion, the research is expected to reveal fundamental principles of non-coding RNA-mediated epigenetic regulation and provide toolkits with potential applications for understanding female-biased diseases and safeguarding against gene escape from X-inactivation.