Isobel Garrett, a sophomore bioengineering major at MIT, studied the differences between classes of alkylating agents in glioblastoma cell lines.
In the field of cancer biology, there has been a long-held assumption that alkylating agents work in similar ways as they all add alkyl groups to DNA. BSRP 2021 has been an amazing experience. Not only did I meet a group of passionate students with a wide range of interests and specialties, but I found a welcoming community. At the Broad I gained valuable research experience from incredible scientists, but I also learned leadership and communication skills applicable to any scientific field. This program will definitely challenge you, but support from mentors, instructors, and the cohort make the expectations more than achievable and the experience simply spectacular.However, each class of these agents causes unique types of DNA adducts. These adducts are repaired through different DNA damage repair (DDR) mechanisms and may not activate the same downstream apoptotic pathways. Understanding the cellular response and resistance to different classes of alkylating agents may provide insight into how to better use these agents in the clinic. To elucidate distinctions between these classes, I examined differentially expressed genes and differential CRISPR dependencies between resistant and sensitive cell lines for eight alkylating agents. I then performed a gene set enrichment analysis (GSEA) on these results to better understand differential activity of DDR and apoptotic pathways. These analyses revealed that class distinctions were not a good predictor for pathway activity. Instead, alkylating agents within a class often showed differing behaviors. This information will provide a better understanding of these agents and may lead to new methods that combat resistance to chemotherapy.
Project: Investigating Differences between Classes of Alkylating Agents in Glioblastoma Cell Lines
Mentora: Simona Dalin, Rameen Beroukhim, Beroukhim Lab