A major challenge in Friedreich’s ataxia research is understanding how the expanded GAA mutation within the FXN gene causes the gene to become switched off. Because restoring FXN activity is the basis of many therapeutic strategies, identifying the mechanisms responsible for gene silencing is critical. This question is particularly important in heart cells, as cardiac disease affects most individuals with Friedreich’s ataxia and is a major contributor to mortality.
This project will investigate how multiple layers of epigenetic regulation contribute to FXN silencing in heart cells derived from patients. Researchers will examine how the gene’s position within the cell nucleus, the organization of DNA surrounding the gene, and proteins that regulate chromatin structure work together to suppress FXN expression.
By defining the mechanisms that drive FXN silencing in disease-relevant cells, this work could identify new opportunities to reactivate the gene and improve emerging therapies designed to restore frataxin production.