Sasha Sengelmann L&S Biological Sciences
Using OpenST to Investigate DNA-PKcs Inhibition in Glioblastoma
Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, exhibits profound resistance to radiotherapy (RT), limiting treatment efficacy and driving recurrence. A key mechanism underlying this resistance is the repair of radiation-induced DNA damage through non-homologous end joining (NHEJ), largely facilitated by DNA-PKcs (encoded by the PRKDC gene). While prior research has shown that pharmacological inhibition of DNA-PKcs with M3814 enhances radiosensitivity, its broader effects on the tumor microenvironment remain unknown.
This project employs Open Spatial Transcriptomics (OpenST), a novel approach that preserves spatial context to examine how DNA-PKcs inhibition and RT reshape tumor, stromal, and immune environments in GBM. Unlike bulk or single-cell RNA sequencing, OpenST enables localized analysis of gene expression and immune dynamics that drive treatment response and progression.
Findings from this study will further our understanding of how DNA-PKcs inhibition in the context of RT changes the tumor and microenvironment, thereby leading to the potential for novel therapeutic development for improving GBM treatment and patient outcomes.
Message To Sponsor
Thank you so much for supporting my research this summer! I am incredibly grateful for the opportunity to further my experience with cutting-edge genomic technologies and computational biology. This project marks a significant personal milestone in my journey toward a future in scientific research, and I am humbled by the chance to contribute to work that addresses urgent medical challenges and ultimately helps patients.