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.