Federal Grant Award Summary

Brown University received a $116,510 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), effective June 17, 2026, with completion targeted by May 31, 2028. This mentored K99 award funds research investigating chromatin-based mechanisms that link transcriptional dysregulation to genome instability in neurodevelopmental disorders, specifically focusing on how dysregulated histone H3 lysine 4 (H3K4) methylation compromises genome integrity in human neurons and contributes to autism spectrum disorder, intellectual disability, and epilepsy pathogenesis.

The research deliverables include mechanistic studies using isogenic induced pluripotent stem cell-derived cortical neurons with patient-relevant mutations to characterize how three key epigenetic regulators (ASHIL, KMT2C, and KDM5B) control chromatin structure and DNA repair capacity. The project applies integrated multi-omic approaches including CUT&TAG, Micro-C, Paired-Damage-Seq, CUT&RUN, and RNA-Seq to map H3K4 methylation patterns, determine three-dimensional chromatin topology, identify oxidative DNA lesions and repair synthesis, and correlate damage hotspots with altered gene expression patterns. These findings are intended to illuminate shared pathogenic mechanisms across neurodevelopmental disorder-linked genes and advance understanding of epigenetic regulation of DNA repair processes.