Project: Mismatch repair proteins in homologous recombination and genome stability
Description: 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 Msh2, Msh3, and Msh6 are required not only to correct polymerase errors following DNA replication, but also to ensure the fidelity of homologous recombination (HR). HR is typically is considered a high-fidelity mechanism of DNA repair, but in the absence of the Msh proteins, it frequently utilizes a mismatched, or “homeologous”, donor sequence. This unrestrained recombination can result in hyper-recombination and cause genome rearrangements.
My project aims to define the heteroduplex rejection pathway in budding yeast. To do so, I will use pathway analysis in combination with proximity ligation assays that measure two critical intermediates in the HR pathway, the nascent and the extended D-loop, which we predict will be targeted by the Msh proteins. I will then reconstitute these pathways in vitro using purified budding yeast proteins. Ultimately, the goal of my work is to address the contribution of loss of regulation of the HR pathway to carcinogenesis in MMR deficient tumors.
2019 – PhD in Genetics, University of Chicago
2019 – Master’s in Genetics, University of Chicago
2012 – Bachelor’s in Biology, Carleton College
Awards and Fellowships:
2021 – A.P. Giannini Foundation Postdoctoral Research Fellowship and Leadership Award
2020 – UC Davis Oncogenic Signal and Chromosome Biology Postdoctoral Fellowship Program
2017 – Honorable mention for the University of Chicago Biological Sciences Division Teaching Award
2013 – University of Chicago Genetics and Regulation Training Grant
2011 – NIH Summer Student Intramural Research Training Award Fellowship
2009 – Kolenkow-Reitz Fellowship for Undergraduate Research