Named Grant:

The “Larger than Life” Pediatric Project Grant

About the Investigator:

Prof. Meshorer has a long-term interest in how stem cells self-renew and differentiate, and how these processes are regulated by the proteins that package nuclear DNA.  He received his BSc, MSc and PhD degrees from the Hebrew University of Jerusalem, and returned there as a faculty member after postdoctoral training in stem cell biology at the National Cancer Institute of the US National Institutes of Health.

About the Research:

Glioblastoma (GBM) is the most frequent malignant brain tumor, and it is challenging to treat.  Comprehensive sequencing of the genomes of glioma cells from a number of pediatric and adult patients has revealed various mutations that recur among patients with GBM and appear to drive tumor development.  How these mutations drive malignancy is not well understood.

A single driver mutation occurs frequently in a type of glioma that occurs only in pediatric patients, known as pediatric diffuse intrinsic pontine glioma (or DIPG).  This mutation is known as H3.3K27M, and it affects a protein that regulates gene expression.  This researcher recently established a system to study the function of the H3.3K27M protein in embryonic stem cells (ESCs) derived from mice.  The laboratory will monitor the effect of the protein carrying the H3.3K27M mutation in undifferentiated mouse and human ESCs, and in ESC-derived oligodendrocyte progenitor cells (OPCs), the cells of origin of GBM.

These experiments will identify specific mechanisms by which this mutation may drive malignancy, providing insights into the mechanisms underlying childhood DIPG development and potentially identifying pathways for therapeutic intervention.