Post-doctoral Fellowship Grant Awarded to Minhui Su

Brain function involves the firing of neurons to deliver information. Unfortunately, neuronal activity also promotes diffuse intrinsic pontine glioma (DIPG) growth and disease progression. We have found that like normal glial cell types, DIPG cells can become integrated into neural circuits. Some DIPG cells form synapses with neurons, similar to a normal glial precursor cell that receives synaptic inputs from neurons. This synaptic communication between neurons and DIPG cells results in electrical currents that promote DIPG growth. Membrane depolarization alone is sufficient to drive DIPG proliferation1, but we don’t yet know
which voltage-sensitive mechanisms promote tumor progression. I used CRISPR/Cas9-based genetic screening to identify key genes for DIPG cells to interact with neurons and grow in the tumor microenvironment. My screening results suggest that voltage-gated calcium channels may play crucial roles in converting electrical activity to promote DIPG growth. Therefore, I propose to study voltage-sensitive calcium channel signaling in DIPG, and compare it with neural stem and progenitor cells in the developing brain. The proposed research on voltage-dependent regulation of DIPG may elucidate novel therapeutic targets for DIPG.