Sasha Sengelmann Rose Hills
Targeting DNA Repair to Drive Immune Activation in Glioblastoma
Despite standard-of-care radiotherapy (RT) and chemotherapy, glioblastoma (GBM) remains one of the most treatment-resistant and aggressive forms of cancer. A critical driver of this resistance is the tumor’s ability to repair radiation-induced DNA damage, a pathway largely regulated by an enzyme called DNA-PKcs. In preliminary data, I have shown that inhibiting DNA-PKcs enhances radiosensitivity in GBM. DNA-PKcs inhibition also induces immune signaling following RT, suggesting that combining DNA damage with immunotherapy could be a promising therapeutic approach.
This project investigates the mechanisms underlying this immune activation. I will test whether DNA-PKcs inhibition combined with RT activates innate immune signaling through cytosolic DNA sensing via cGAS/STING or RNA sensing via MAVS. By determining which pathway drives inflammatory signaling across different GBM models, this work will reveal how DNA damage can be leveraged therapeutically to enhance immunotherapy in GBM tumors that fail to respond to RT.
Message To Sponsor
Thank you for supporting my research this summer. I am beyond grateful for the opportunity to investigate how DNA damage repair and immune signaling intersect in glioblastoma, a disease where new therapeutic strategies are urgently needed. This project represents a meaningful step in my development as a cancer researcher, and I am excited to contribute to work that could improve treatment approaches for patients. Your support makes this work possible, and I truly appreciate the opportunity.