Weekly lecture series hosted by the Center for Neuroregeneration and Department of Neurosurgery. 

Tuesday 9am-10am in Dunn Tower Guadalupe and Pecos Conference Room

Title: Neurodegeneration: The Role of Genome Organization and Stability

Abstract: We investigate how the genome shapes brain function and its disruptions in disease and aging. Using post-mortem human brain samples and mouse models (including CK-p25), we find that persistent neuronal DNA double-strand breaks (DSBs) —an early hallmark of Alzheimer’s disease (AD)—are linked to somatic genome instability. Excitatory neurons in AD are enriched for somatic mosaic gene fusions and structural variants, especially within populations bearing DNA-repair and senescence signatures. Further, DSB-burdened neurons show progressive, multiscale disruption of 3D genome organization that tracks with transcriptional changes in neuronal genes. Overall, we describe the disruption of genome stability and the 3D genome organization by DSBs in neurons as pathological steps in the progression of neurodegenerative diseases.