Validation of GBM Chemosensitizing Hits From in vivo CRISPRi Screen
Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. Although research has enhanced GBM diagnosis and clinical stratification, overall patient outcome has not significantly improved. This is because GBM is incurable with current treatments, which include surgery, radiation therapy, and Temozolomide (TMZ) chemotherapy. The development of CRISPR-Cas9 systems presents opportunities to study human diseases, and it can be leveraged to create therapeutics. Specifically, CRISPR interference (CRISPRi)-based screens help study GBM dependencies and growth vulnerabilities without DNA damage. I have assisted with in vivo and in vitro parallel CRISPRi screens in combination with TMZ treatment in order to identify potential chemosensitizers for GBM. As a result, we identified multiple genes that warrant further study to determine if they can serve as therapeutic targets. I will begin with validating target knockdown in vitro using tissue culture and molecular biology techniques. Then, I will perform experiments with small molecule inhibitors of these hits to determine if co-treatment of the inhibitor and TMZ can kill GBM cells more efficiently compared to standard-of-care TMZ treatment.
Message to Sponsor
- Major: Molecular and Cellular Biology
- Sponsor: Leadership Fund
- Mentor: Jennifer Doudna