Gabriele Dall'Aglio

Project Summary: X-linked dystonia–parkinsonism (XDP) is a rare neurodegenerative disorder found almost exclusively in the Philippines, caused by a mutation in the TAF1 gene. The disease devastates the striatum (particularly medium spiny neurons) leading to progressive dystonia and parkinsonism. Despite knowing the genetic culprit, we still don't understand how this mutation triggers neurodegeneration.

A striking feature of XDP is its characteristic dorsoventral degeneration pattern in the striatum. This creates a major analytical challenge: the striatum naturally shows strong dorsoventral gene expression gradients even in healthy tissue. Conventional methods struggle to separate this normal regional variation from disease-related changes, making spatial resolution critical for understanding XDP pathology.

Recent advances in single-cell omics and spatial transcriptomics now allow us to probe molecular mechanisms at unprecedented resolution. My project combines single-cell RNA sequencing with Slide-seq spatial transcriptomics and machine learning approaches to map gene expression differences between healthy and XDP striatum. By preserving spatial information, I aim to identify the molecular drivers of selective neuronal vulnerability and reveal why certain striatal populations degenerate while others remain intact.