Federal Project Grant Award Summary

The University of Texas Southwestern Medical Center received a $384,065 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), effective June 16, 2026, with completion targeted for May 31, 2031. This award supports fundamental research investigating the molecular mechanisms underlying PFA (Posterior Fossa A) ependymoma, a rare and aggressive pediatric brain tumor characterized by epigenetic dysregulation rather than genetic alterations. The research focuses on elucidating the crosstalk between EZHIP (EZH1/2 inhibitory protein) and PRC2 (Polycomb Repressive Complex 2), examining how aberrant EZHIP expression disrupts PRC2's epigenetic regulatory function in tumor cells.

The funded research will employ structural biology and molecular analysis techniques to characterize the precise mechanisms by which EZHIP inhibits PRC2 enzymatic activity and stalls the complex on chromatin, resulting in the global loss of H3K27ME3 (trimethylated histone H3 lysine 27) repressive marks that define the disease. By identifying the specific interactions between EZHIP and multiple PRC2 components—including its two functional variants, PRC2.1 and PRC2.2—this investigation will advance fundamental understanding of pediatric brain tumor pathophysiology and potentially identify therapeutic targets for intervention in this devastating disease.