Glioblastoma (GBM) is the most aggressive and deadliest form of brain cancer. Despite advances in surgery, chemotherapy, and radiation therapy, most patients survive for only about 15 months after diagnosis. One of the biggest challenges in treating GBM is that the tumor is highly complex, with different regions behaving differently. This makes it difficult for doctors to target the entire tumor effectively, leading to treatment resistance and recurrence.

Recent research suggests that chemical changes in messenger RNA (mRNA), may play an important role in GBM growth. One such chemical change is called 5-methylcytosine (m5C), which can regulate gene expression. However, scientists do not yet fully understand how m5C affects GBM development, nor do they know how its distribution varies within different parts of a tumor.

This project will develop a new method to map m5C modifications at the single-cell level within intact tumor tissues. Unlike current approaches, which analyze cancer cells in bulk and lose valuable spatial information, our method will allow researchers to see exactly where these modifications occur within different regions of a tumor. By applying this technique to patient-derived tumor models, we will study how m5C modifications contribute to GBM’s aggressive nature.

In addition, we will investigate whether altering m5C levels affects GBM tumor growth and invasion. By using genetic tools to reduce or increase m5C levels, we will assess how this modification influences cancer cell behavior, including how quickly tumors grow and how far they spread within the brain. These experiments will help us determine whether targeting m5C could be a new strategy for slowing down GBM progression.

The findings from this study could have a significant impact on the future of brain cancer treatment. By identifying new molecular markers for GBM progression and therapy resistance, this research could help doctors develop more precise and personalized treatment strategies. Additionally, since RNA modifications like m5C are found in other cancers, this work may have broader applications beyond GBM, potentially leading to new treatments for multiple types of cancer. This proposal aims to uncover new insights into how RNA modifications drive tumor growth, ultimately paving the way for innovative therapies to improve patient outcomes.