DNA damage & neurodegeneration

Every cell sustains tens of thousands of DNA lesions per day. When the repair machinery cannot keep pace, damage accumulates — and a growing body of evidence places this accumulation among the causal drivers of aging. The clearest demonstration comes from the premature-aging syndromes: inherited defects in DNA repair, such as Cockayne syndrome and xeroderma pigmentosum, that compress a lifetime of degeneration into a few years.

We study how the cell senses and responds to genomic damage. By tracing the signalling cascades that fire downstream of damage, we aim to understand why some genomes age gracefully and others do not — and, crucially, where along that cascade we might intervene.

The brain is uniquely vulnerable to this damage. Its neurons are largely post-mitotic, its DNA-repair capacity is comparatively low, and its energy demands are relentless — a combination that lets lesions and dysfunctional mitochondria accumulate over a lifetime. It is no coincidence that the premature-aging syndromes caused by DNA-repair defects are so often dominated by neurological decline.

We use these accelerated-aging disorders as a window onto normal brain aging, studying how genomic instability, NAD⁺ depletion and failing mitochondrial quality control converge to drive neurodegeneration — and searching for metabolic and pharmacological interventions that protect neurons, preserve cognitive healthspan, and may ultimately bear on common conditions such as Alzheimer's and Parkinson's disease.