This project seeks to elucidate the basis for platinum-resistance observed in clear cell ovarian carcinomas by capitalizing on the high rate of mutations at and loss of protein expression for the AT-rich interactive domain 1a (ARID1A) locus. This gene encodes a key component of the chromatin remodeling complex BAF which can lead to epigenetic changes in gene regulatory regions. Using in vitro and in vivo systems, we plan to characterize the role of ARID1A with regards to sensitivity to platinum-based chemotherapy as well as combinatorial regimens with epigenetic therapies and platinum-chemotherapy.

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