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Deciphering the mechanisms and relevance of replication stress in ovarian cancer
The major goal of this work is to generate unique three-dimensional models called organoids from the cells thought to be the cells of origin for ovarian tumors, those from the fallopian tube or the surface of the ovary, from patients with either no genetic mutations or those carrying mutations in genes which predispose to ovarian cancer development, like BRCA1 or BRCA2. Cells carrying such mutations often have trouble doubling their DNA so they can divide, and this difficulty can lead to changes in the cells that make them transition to cancer. We plan to use our organoid models to study whether the changes in these cells due to their problems with doubling their DNA lead these cells to secrete detectable proteins in the blood or pelvic fluid which might then be used to generate an early detection test. In the past year, despite the difficulties of COVID, we have generated five stable organoid models and begun to characterize them.
In the coming year, we hope to generate at least another five models and to begin to characterize the problems these organoids have in doubling their DNA and if these problems lead to changes in the cells and secretion of detectable proteins. We have faced significant challenges due to COVID with this project including having our lab shutdown for nearly four months, having difficulty consenting patients and obtaining tissue to generate organoids since we have reopened, and now having disruptions in the supply chain for basic lab supplies (like tubes or pipet tips). Despite these challenges, we are confident we will be able to make progress on this project at least with the organoids we have already generated but may need some extra time to finish our proposed work.