Heal It

Such a step will bring us closer to effective treatment, not only for ICF syndrome but also for other epigenetic diseases.
-Shir Toubiana

Shir Toubiana, an MD/PhD student is a changemaker, helping to unlock some age-old secrets of epigenetics.
Using innovative genomic editing methods, Shir Toubiana succeeded in correcting the DNMT3B gene in pluripotent stem cells of ICF patients.

ICF syndrome is rare but can lead to death before the age of 20 in those affected. In about half the patients, the syndrome is caused by mutations in the DNMT3B gene that is responsible for adding a methyl group to certain regions of the DNA.

Malfunctions in the methylation process disrupt many developmental processes including the regulation of chromosome ends, which can lead to the premature aging of patients’ fibroblasts.

We found that the failure is due to certain molecular barriers that are part of the ‘epigenetic memory’ of patients’ original skin cells. Through chemical manipulation, we were successful in lowering some of these barriers.

The disorder in ICF syndrome patients most likely starts early in their embryonic development. Due to epigenetic memory, the correction of DNMT3B only partially rescues the abnormal characteristics at the chromosome ends – the telomeres. This study teaches us important lessons regarding the strategies that should be pursued for treating inherited epigenetic diseases.

The study was published in the journal eLIFE and includes the research of Shir Toubiana and her supervisor Prof. Sara Selig at the Rappaport Faculty of Medicine together with Dr. Maria Matarazzo of the Institute of Genetics and Biophysics ABT CNR, Italy and colleagues.

MD/PhD student Shir Toubiana
MD/PhD student Shir Toubiana

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Read the publication in eLife: