Senior thesis research leads to potential cancer therapies

Kristan Scott (right) prepares a sample of yeast cells with Alison Gammie, senior lecturer in molecular biology.

For his senior thesis, Princeton molecular biology major Kristan Scott studied a mutant gene linked to colorectal cancer and to the cancer’s ability to resist chemotherapy. Scott helped find the ideal combination of cancer treatments that restored sensitivity to the drugs. This result suggests a potential new chemotherapeutic approach for treating certain cancers.

Scott worked with thesis adviser Alison Gammie, a senior lecturer in the Department of Molecular Biology who oversees a lab with Professor of Molecular Biology Mark Rose. The Gammie lab focuses on the role of mismatchrepair protein mutations in the growth of cancer. These proteins act as a kind of biological spell-check to ensure that genes are free of errors.

Scott focused his work on MSH2, a gene associated with hereditary non-polyposis colorectal cancer, which accounts for roughly 5 percent of all colorectal cancer cases. Mismatchrepair genes can experience mutations that make the MSH2 gene itself a mutant and can lead to colorectal and other cancers with a strong resistance to chemotherapy, Scott said.

Scott examined how the mutations in MSH2 bestow that strong defense against chemotherapy. He worked with the chemotherapy drug cisplatin — frequently used to treat colorectal cancer — and a yeast strain developed by Tim Arlow, a doctoral student in Gammie’s lab. The yeast strain was sensitive to a spectrum of drugs, yet had the defective MSH2 gene. Thus, the researchers knew the yeast should be responding to the treatment and could then better understand why cells with mutant MSH2 genes were resistant to cisplatin.

Scott helped figure out that a combination of cisplatin and a cancer treatment called bortezomib restored the sensitivity of some defective yeast strains to chemotherapy, an important result that expanded on Arlow’s work, Gammie said. The work was funded by the New Jersey Commission on Cancer Research.