Mitchell Valentine

Program: Cancer Biology

Current advisor: Abby M. Green, MD

Undergraduate university: Case Western Reserve University, 2023

Enrollment year: 2024

Research summary
APOBEC enzymes are sources of mutagenesis in many human cancers, with some APOBEC family members even being upregulated following cancer treatment. We will determine the impact of APOBEC expression on therapeutic sensitivity and resistance.

The apolipoprotein B mRNA-editing catalytic polypeptide-like (APOBEC) family of cytosine deaminases are involved in innate immunity and restrict viral pathogenesis through base editing. In recent decades, select members of the APOBEC family of enzymes have been identified as major sources of mutagenesis across many human cancers, including high-grade serous ovarian carcinoma (HGSOC). Specifically, APOBEC3A (A3A) catalyzes the conversion of cytosine to uracil in ssDNA, a source of replication stress that creates an opportunity for endogenous mutagenesis during active replication. Recent publications have linked A3A upregulation and mutagenic activity with cancer cell evolution, metastasis, and therapeutic resistance. Despite these observations, many questions remain regarding the mechanism(s) through which such phenomena develop and persist. We are investigating the mechanisms through which A3A-mediated mutagenesis regulates cancer phenotypes, with a focus on aggressive HGSOC.

Graduate publications