With continued support, WashU researchers are turning complex genetic puzzles into clinical progress.
When a child is diagnosed with a brain tumor, families need answers — and hope. WashU researchers are working to provide both, and your support makes that work possible.
Led by David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology, a recent WashU study has uncovered critical insights into the biology of pediatric pilocytic astrocytoma (PA) — one of the most common low-grade brain tumors in children. Using cutting-edge stem cell models, Gutmann and his team identified key genetic mechanisms that drive tumor growth, revealing new potential targets for future therapies.
The research, published in Genes & Development, focuses on how two common genetic changes — the loss of the NF1 gene and a BRAF gene fusion — cause tumor cells to grow by activating the MEK/ERK signaling pathway. Scientists have long known this pathway is involved, but exactly how it contributes to tumor growth in the developing brain has remained a mystery.
By modeling the disease using human induced pluripotent stem cells (hiPSCs), the WashU team discovered that a protein called β-catenin is a crucial link in this chain. Two other molecules, IRX2 and NPTX1, help increase β-catenin activity — one by ramping up its production, the other by preventing its breakdown.
The team confirmed these findings in patient-derived tumor samples and lab models. When they blocked the MEK pathway or β-catenin itself, tumor cell growth slowed significantly — a promising signal for the development of new, more targeted treatments for children with PA.
This kind of research — innovative, rigorous, and focused on patient impact — is only possible because of faculty expertise and forward-looking investment. With your gifts to research, you create a culture that empowers researchers to ask bold questions, follow the science, and keep children at the center of every discovery.