Yacoub Haydin
Pronouns:
Research Mentor(s): WajdAl Holou
Research Mentor School/College/Department: /
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Yacoub Haydin, Wajd Al-Holou, Sunita Shankar
Abstract
Glioblastoma (GBM), is the most common primary brain tumor. It is a lethal disease with a median survival of 15 months characterized by treatment resistance, aggressive brain invasion, and inevitable recurrence. Less than 10% of patients survive beyond 5 years, despite surgical resection combined with temozolomide/radiation (TMZ/IR) therapy. Recently, using a longitudinal intracranial mouse model of GBM patient derived neurospheres, we identified THY1 as a key protein, involved in treatment resistance. While only 5% of neurospheres had high THY1 expression, TMZ/IR therapy in this mouse model, enriched for cells that mostly express THY1. This was accompanied with increasing stem-cell like gene expression, a hallmark of therapy-resistant cancer stem cell (CSC) populations. We believe that these preexisting CSC populations likely drive treatment resistance due to their ability to self-renew, differentiate, and expand to repopulate tumors post-therapy. We also developed in vitro models to recapitulate this phenomenon. In patient derived organoids, inducible knockout of THY1 led to increased sensitivity to TMZ/IR. In U87 glioma cells, grown as neurospheres, overexpression of THY1 was sufficient to increase resistance to TMZ/IR therapy. This was accompanied with increased stemness and a more neuronal precursor like phenotype. Currently, we are interrogating proteins that are differentially expressed due to THY1 overexpression in the U87 model, using mass spectrophotometric analyses. Leads obtained from this analysis will be validated using immunoblotting.
