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Hill Lab Ovarian Cancer Organoid and Tissue Bank:
As the Hill lab continues to generate and profile ovarian cancer organoid cultures from new patients coming to BWH/DFCI to understand disease mechanisms and to try to determine if organoid functional assays on each patient's culture will be useful in predicting patient response, we continue to generate a large bank of organoid cultures across all ovarian cancer subtypes and also generate organoids from benign fallopian tube, ovarian surface epithelium, and other matched normal cells. Please contact Dr. Hill for questions about the bank or to collaborate.
My lab focuses on understanding the role of the DNA damage response in ovarian carcinogenesis, the immune response, and therapeutic sensitivity and resistance.
Patients with High Grade Serous Ovarian Cancer (HGSC) have limited therapeutic options. Immune therapies have had limited effect thus far, however, genomic analysis suggests that up to 50% of HGSCs have genomic alterations that may confer a DNA damage repair defect, making therapies that target repair defects, like carboplatin and PARP, CHK1, WEE1, and ATR inhibitors, important additional options. However, we have no means of predicting which genetic alterations confer specific repair defects and which defects translate to a therapeutic response in the patients.
A model system that allows for functional assays to assess for DNA damage repair defects, the anti-tumor immune response, and prediction of response to therapies targeting repair defects or the immune system is needed. Organoids are three-dimensional structures derived from human tumor tissue that anatomically and functionally mimic the tumor from which they were derived allowing for functional analysis of the parent tumor. My lab is able to reproducibly grow patient-derived epithelial ovarian cancer (HGSC, low grade serous, clear cell, and mucinous), fallopian tube, and ovarian surface epithelium organoids and utilize molecular and cellular biology, immunology, and imaging techniques to understand the functional ability of these organoids to perform different types of DNA damage repair, such as the protection of stalled replication forks, and to engage the anti-tumor immune response.
Our initial work has indicated that stalled fork protection defects are highly prevalent in ovarian cancers and that such defects may lead to ovarian carcinogenesis and alterations in ovarian cancer cells that make the entire tumor more resistant to therapy. The goal of our research is to utilize molecular and cellular biology, immunology, sequencing, and imaging techniques in cell lines, pateint-derived normal and ovarian cancer organoids, and mouse models to understand the role of DNA damage repair defects in ovarian carcinogenesis, the anti-tumor immune response, and therapeutic sensitivity and resistance. 

Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient TP53 Mutant Uterine Carcinomas Is Linked to the Summation of LKB1-AKT-p53 Interactions. Cancers (Basel). 2021 May 03; 13(9).
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Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer. Cancer Res. 2021 01 01; 81(1):158-173.
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Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer. Cancers (Basel). 2020 May 11; 12(5).
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Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2019 12 01; 5(12):1731-1738.
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Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer. J Clin Oncol. 2019 10 20; 37(30):2786-2794.
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Predictive Potential of Head and Neck Squamous Cell Carcinoma Organoids. Cancer Discov. 2019 Jul; 9(7):828-830.
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3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. Lab Chip. 2018 10 09; 18(20):3129-3143.
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Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids. Cancer Discov. 2018 11; 8(11):1404-1421.
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Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage. Proc Natl Acad Sci U S A. 2016 11 29; 113(48):E7701-E7709.
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BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair. Mol Cell. 2015 Feb 19; 57(4):636-647.
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Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage. Genes Dev. 2014 Sep 01; 28(17):1957-75.
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BRCA1 pathway function in basal-like breast cancer cells. Mol Cell Biol. 2014 Oct; 34(20):3828-42.
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BRCA1 is required for postreplication repair after UV-induced DNA damage. Mol Cell. 2011 Oct 21; 44(2):235-51.
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BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol Cell Biol. 2011 May; 31(10):1972-82.
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Pagetoid lesions of the vulva: a collision between malignant melanoma and extramammary Paget disease. Int J Gynecol Pathol. 2008 Apr; 27(2):292-6.
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