Investigating how neuron-glioma interactions drive radioresistance in diffuse midline gliomas
Mentor Name: Mariella Filbin
Diffuse midline gliomas (DMGs) are a devastating group of diseases with a median survival of 9-12 months and no long-term survivors. Due to obstacles posed by drug delivery and resistance as well as the inability to resect DMG, focal radiation remains the standard of care; however, radioresistance ultimately arises in all DMG cases, leading to tumor recurrence in 100% of patients. Our lab has shown that there is an increase in communication between neurons and DMG cells in response to radiation therapy, which is speculated to promote therapeutic resistance in DMGs. Our project aims to evaluate the role of synaptic activity in promoting radiation resistance in DMGs and to investigate whether disrupting neuron-tumor cell interactions could resensitize DMGs to radiation, improving their response to therapy. We plan to co-culture three patient-derived DMG cell lines with electrically-active excitatory neurons to stimulate synaptic communication and compare the results to DMG cells grown alone. Both cell types will then be exposed to radiation to assess differences in DNA damage-repair dynamics as a result of surrounding neuronal activity.
