The exact process by which the GAA triplet repeat expansion silences the FXN gene remains unclear, making it difficult to develop effective treatments. This research aims to elucidate the epigenetic mechanisms driving FXN gene silencing and explore potential therapeutic interventions using tools targeting these mechanisms. Epigenetic changes are heritable modifications attached to DNA that impact gene activity without changing the DNA sequence of genes. Using cutting-edge technologies, Dr. Guan will profile epigenetic modifications in FA patient-derived stem cells and neurons derived from these cells and compare them with those in isogenic control cells, where the GAA repeats are removed. This work will advance our understanding of the epigenetic regulatory mechanisms underlying FA pathology. Additionally, Dr. Guan will employ CRISPR-based epigenetic editing tools to modify the epigenetic landscape, testing whether these epigenetic changes directly cause FXN silencing. The insights gained will improve our understanding of FA’s underlying biology and may lead to new therapies that target these epigenetic abnormalities.
Postdoctoral Research Award | Mechanism or Pathway of Disease
Unraveling Epigenetic Mechanisms and Therapeutic Strategies for FXN Silencing in Friedreich’s Ataxia
Grant Awarded | Mar 2025
Xiaonan Guan, PhD
New York Genome Center
Active
The FARA Grant Program is proud to award a Postdoctoral Research Award to Xiaonan Guan, PhD, at the New York Genome Center, to understand what causes frataxin gene silencing and how to reverse it.
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