25 July 2024

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NIH award leads to deeper study of brain malformations

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How seizures, epilepsy and other brain malformations develop from genetic variants is not fully understood, but a new National Institutes of Health (NIH) award will pave the way toward understanding the cause and potentially lead to new therapies.

Adams School of Dentistry’s Di Wu, PhD, along with UNC Eshelman School of Pharmacy’s Erin Heinzen, Pharm.D., Ph.D, are co-investigators for a newly funded study, Genotype-Informed Single-Cell Transcriptomic Profiling of Mosaic Brain Tissue. This NIH award of more than $420,000 will allow for the deep study of individual cells comprising these brain tissue specimens to better understand how these genetic variants cause disease and how we can better treat these conditions.

New (non-inherited) genetic variants can arise as cells divide during embryonic development and give rise to mosaicism — sets of cells that are genetically different from one another. Such variants have been shown to cause seizures and brain malformations. The abnormal mosaic brain tissue can sometimes be surgically removed to treat the seizures caused by these genetic variants.

This proof-of-concept study will look at tissue composed of a mixture of cells with and without a genetic variant that causes a rare brain malformation to study the effect of the variant on gene regulation in different types of brain cells.

The team hypothesizes that their study will reveal reproducible convergent and divergent cell-type-specific disease mechanisms across individuals with the same pathogenic variants and across genes implicated in the same brain malformation. If successful, they will establish a powerful research approach that leverages somatic mosaicism to inform cell types involved in disease, identify the functional changes that accompany neurological and neuropsychiatric diseases and illuminate new therapeutic strategies.

Source: https://dentistry.unc.edu/