Understanding how genomic instability leads to the transcriptional misregulation of genes central to neuronal homeostasis is critical for understanding how persistent DNA damage drives A-T pathology. This project seeks to advance understanding of the relationship between DNA damage, its transcriptional consequences and cellular inflammation that triggers senescence by combining cutting-edge technologies (DNA combing, BLISS, spatial transcriptomics) with our novel human A-T patient stem cell-derived brain organoid model to test the novel concept that senostatics targeting the cGAS and STING pathway can slow neurodegeneration in A-T.

Project members

Lead investigator

Dr Julio Aguado

Research Fellow
Wolvetang Group