Ananya Gera
Pronouns: she/her
Research Mentor(s): Robert Doherty
Research Mentor School/College/Department: Pediatrics / Medicine
Program: UROPF
Session: Session 2 (10:00am – 10:50am)
Authors: Ananya Gera
Abstract
The diffuse midline glioma (DMG) is a type of pediatric brain tumor with no currently effective treatment and a poor prognosis. ONC201 is a pyrimidine drug that is the only effective therapy for DMGs, prolonging progression free and overall survival. ONC201 is more effective in thalamic DMGs than brainstem DMGs; the difference in regional response is correlated with EGFR (epidermal growth factor receptor) expression: high EGFR expression in the brainstem corresponds with a lower effectiveness of the drug and low EGFR expression in the thalamus corresponds with a higher effectiveness of the drug. To understand how this difference in EGFR status arises, we first need to identify when the brainstem and thalamus start to exhibit high and low amounts of EGFR, respectively. To assess the difference in EGFR status we carried out a time course of EGFR immunofluorescence on an in vivo mouse model of thalamic and brainstem DMGs. We have shown there is no difference in EGFR expression between thalamic DMGs and brainstem DMGs up to 13 days. We will further assess EGFR status at timepoints from 20 to 60 days. Once we have identified the timing of the change in EGFR status between thalamic and brainstem DMGs in this mouse model, we will assess the underlying mechanisms that may underlie or contribute to this difference. The long term aim of this project is to identify potential therapeutic targets that may be used in combination with ONC201 to improve treatment efficacy in the brainstem DMGs.
