Sarah Hill, MD, PhD

Sarah Hill, MD, PhD

Sarah Hill, MD, PhD

About Project

Deciphering the mechanisms and relevance of replication stress in ovarian cancer
precursor cells


PROJECT SUMMARY

Patients with high grade serous ovarian carcinoma (HGSC) present at late stage with difficult to treat disease, making early detection critical. There are currently no biomarkers to identify early stage disease. Many ovarian cancer patients carry familial mutations in the DNA damage repair genes BRCA1 and BRCA2. At present, it is not clear what the exact role of these proteins is in preventing the formation of ovarian tumors. One major function of these proteins is in protecting the DNA when a cell is dividing and has to double its DNA in a process called DNA replication. We hypothesize that it is this function of BRCA1 and BRCA2 in protecting DNA during replication that is altered in ovarian cancer precursor cells. We further suspect that this alteration can contribute to both the generation of cancer and altered production of proteins in these cells which may be secreted and serve as early detection markers in these patients. We plan to generate three-dimensional models of normal ovarian cancer precursor cells called organoids from patients carrying these genetic mutations and from patients with a strong family history of ovarian cancer but no familial mutation. We will test these models to determine if the cells have problems protecting DNA during replication and ask whether such problems might lead to these normal cells becoming tumor cells. Ultimately, we seek to identify if these problems lead to expression of different proteins in these cells compared to normal expression, which could be used to detect early cancer lesions.


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