Post-doctoral Fellowship Grant Awarded to Tara Barron

Pediatric high-grade gliomas such as diffuse intrinsic pontine glioma (DIPG) are the leading cause of brain cancer-related death in children. While enormous progress has been made in recent years for many forms of cancer, DIPG remains seemingly intractable, indicating that fundamental aspects of glioma growth are not yet well understood. A lack of effective treatment for DIPG can be partially attributed to the diffusely infiltrating characteristics of the tumor. Rather than creating a dense and circumscribed tumor cell mass, DIPG diffusely invades the normal brain tissue, making resection impossible and providing the opportunity for glioma cells to interact with other cells in their environment, including neurons. Recent work from our group has demonstrated that neuronal activity powerfully drives DIPG progression. We aim to gain further insight into the active communication between neurons and glioma cells in order to shift our view of DIPG from an isolated disease to an active and integrative system and leverage these findings for more effective therapeutic strategies. Medications that decrease neuronal activity are commonly given to children with DIPG to treat anxiety and nausea. Some of these medications increase signaling of GABA, which has an inhibitory effect on neurons and could thereby inhibit DIPG growth. On the other hand, it is possible that DIPG cancer cells may directly respond to GABA, which could either increase or decrease DIPG growth. We aim to determine the role of neuron-to-glioma GABA signaling in DIPG and its effect on DIPG growth to inform whether commonly-used drugs that affect GABA signaling may be beneficial or detrimental to give to children with DIPG.