PhD in Genetics from University of Chicago

Mutations in the mismatch repair (MMR) genes are observed in ~20% of all human cancers, accounting for a high proportion of stomach, pancreatic, colon, and endometrial carcinomas. The activities of the MMR proteins are required not only to correct polymerase errors following DNA replication, but also to ensure the fidelity of homologous recombination (HR). HR is a high-fidelity mechanism of DNA repair, but in the absence of the Msh proteins, it frequently utilizes a mismatched donor sequence, which has the potential to result in genome rearrangements.

 

To gain insight into the mechanism through which the Msh proteins regulate HR, my project aims to define the heteroduplex rejection pathway in budding yeast using genetic analysis in combination with biochemical reconstitution experiments. Ultimately, my goal is to understand the contribution of loss of regulation of the HR pathway to carcinogenesis in MMR deficient tumors by transitioning what I have learned in budding yeast to mammalian cells.