Liu & de Nooij Labs receive a research award from Friedreich’s Ataxia Research Alliance (FARA)

The ultimate goal of the Friedreich’s Ataxia Research Alliance (FARA) grant program is to further therapeutic discovery and development by funding projects related to basic, translational and clinical research. The program is designed to fund established and new investigators in the FA field, both in academic and industry settings and promote collaborations among scientists.

In 2021, FARA funded 16 new grants and 38 received continued funding from previous years. 7 of the new awarded grants were to investigators who had not previously received FARA funding. Currently, researchers in 10 countries are receiving funding from the FARA research grant program. 

Shawn Liu, PhD & Joriene de Nooij

Funding period: Jun 1, 2022 - May 31, 2023

Rescue of Friedreich’s Ataxia cells by DNA methylation editing of the FXN gene

Reactivation of the silenced FXN gene represents an attractive therapeutic strategy because the FXN coding sequence remains intact in the vast majority of FRDA patients. However, the molecular mechanisms underlying the silencing of FXN are under active investigation. One of these mechanisms is DNA hypermethylation, a code that is written onto genes, but goes beyond the genetic code - thereby called epigenetic - and consist of chemically changing the structure of one of the 4 DNA building blocks, by adding methyl groups. DNA hypermethylation of the FXN gene has been documented in FRDA patients and has been correlated with FXN transcriptional deficiency and age of disease onset. However, the functional significance of this DNA methylation event to the pathogenesis of FRDA remains unclear due to the lack of a precise molecular tool to manipulate this methylation event in the disease-affected cells. Dr. Liu has developed a CRISPR-based molecular tool to precisely edit DNA methylation. With this new tool, his group will test whether demethylation of the FXN gene may reactivate its expression and rescue FRDA-associated cellular defects. In collaboration with Dr. Joriene De Nooij’s laboratory (co-principal investigator) at Columbia University Medical Center, Dr. Liu will apply the DNA methylation editing tool to demethylate FXN in sensory neurons derived from FRDA-patient induced pluripotent stem cells (iPSCs), and in Dorsal Root Ganglia sensory neurons obtained from a mouse model of FRDA. They will then phenotypically characterize the in vitro and in vivo DNA methylation-edited neurons. Precise editing of FXN methylation will permit an evaluation of the functional significance of this epigenetic event in the pathogenesis of FRDA. Moreover, these studies may demonstrate the therapeutic potential of DNA methylation editing for FRDA.


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