Sarah Johnstone, MD, PhD

Cancer arises from alterations, termed mutations, of a cell’s genetic material (DNA). Understanding how different types of mutations promote cancer cell growth requires precise modeling of these mutations in tumor cells in order to discern how they specifically impact cell function. We propose to do this for two proteins that are frequently mutated in ovarian cancer. These proteins, CTCF and BORIS, bind to the DNA and can change the DNA’s structure to turn genes on or off. However, how their mutations affect the DNA binding for these two proteins and impact ovarian cancer cells is unclear. We propose to generate cellular models of BORIS and CTCF mutations and measure their impact on DNA structure and gene expression. From these data, we will discern the molecular alterations and functional consequences of their mutation. The goal is to define the mechanism by which these frequent mutations impact ovarian cancer cells, with the ultimate hope that such mechanistic insights can lead to novel therapeutic approaches to ovarian cancer.

Location: Dana-Farber/Harvard Cancer Center - Boston
Proposal: Architectural protein mutations rewire ovarian cancer genomes
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