Post-doctoral Fellowship Grant Awarded to David Rogawski

Many previous studies of DIPG focused on studying growth pathways within the tumor cells themselves. However, DIPG tumors receive powerful signals from surrounding neurons that cause the tumors to grow. We will take an innovative approach by searching for new pathways through which neurons signal to DIPG cells. To do this, we designed an experiment in which neurons and DIPG cells are grown together in a dish and found that DIPG growth increases tenfold when neurons are present. Next, we obtained a library of small molecule drugs that block a variety of neuronal signaling pathways. Many of these drugs are known to be brain-penetrant and are FDA-approved for epilepsy, depression, and other neuropsychiatric conditions. Our preliminary studies identified several promising lead compounds that slow glioma growth, including potassium channel blockers, calcium channel blockers, and dopamine modulators. In this fellowship project, we will extend these experiments to additional cell lines and perform further experiments to identify the receptors and characterize how the compounds are affecting glioma growth. Then we will test the lead compounds in mouse models of DIPG. We anticipate that our studies will identify new pathways of neuron-to-glioma communication as well as multiple lead compounds with different mechanisms of action that can be rapidly advanced to clinical trials for DIPG patients.