New Investigator Grant Awarded to Yang Li

Diffuse midline glioma (DMG) is a deadly childhood tumor with no effective treatments. The Histone 3–Lysine-27–Methionine (H3-K27M) mutation occurred in 60-70% of patients with DMG, leading to widespread alterations in histone modifications that drive DMG tumorigenesis. Recent advances in single-cell technologies have characterized molecular signatures in various cell states from DMGs. However, the unique signature of DMGs, genome-wide histone modification alterations, has not yet been studied in clinical samples at single-cell resolution.

This project aims to generate the first comprehensive map of genome-wide histone modifications of DMGs at a refined cell type/state resolution. By utilizing well-established computational pipelines and advanced artificial intelligence models, we will gain a deeper understanding of the genetic and epigenetic dysregulation in DMGs, identify key regulatory elements, and predict the function of genetic risk mutations. This knowledge could pave the way for new targeted therapies and improve DMG outcomes.