PROJECT SUMMARY – TRANSLATIONAL PATHOLOGY CORE The high case-fatality of ovarian cancer makes translational studies essential for advancing treatment and improving outcomes. The Hillman Cancer Center (HCC) Ovarian Cancer (OvCa) SPORE Translational Pathology Core (TPC) will provide four key services to facilitate innovative translational studies: (1) procuring quality-controlled, pathology-reviewed, and clinically-annotated biospecimens, (2) extracting, processing, and storing de-identified clinical data that can be easily integrated with other data types (e.g., genotype, omics, metadata), (3) securely sharing biospecimens and data, and (4) developing patient-derived tumor models for therapeutic and mechanistic studies. The TPC provides these critical services to HCC OvCa SPORE investigators, other NCI-funded OvCa SPOREs, and the greater OvCa research community. A strength of the TPC is the OvCa SPORE Biorepository, established as a part of a previous P50 award to support the translational needs of OvCa researchers. The biorepository enables all persons seen at HCC gynecologic cancer clinics in southwestern PA to donate samples. Consented individuals provide tumor, ascites, pelvic washes, blood, stool, and/or tissue samples for fresh or preserved disbursement. Specimens are longitudinally collected to include samples prior to treatment, throughout the course of clinical care, and at project-specific timepoints. All specimens undergo central pathology review. A novel aspect of the TPC is using primary patient tissues to generate preclinical models to facilitate basic science and preclinical studies. TPC banks single live cell tumor suspensions, isolates and expands primary patient tumor-derived cancer-associated mesenchymal stem cells, and creates mixed cell culture tumor organoids. Primary tumor is also used to generate patient- derived tumor xenografts (PDX) including a new humanized stroma PDX (HS-PDX). HS-PDX can be generated in mice with humanized bone marrow to include a human immune system. TPC will ensure that all samples it collects are accompanied by annotations that will permit linking laboratory analyses with clinical results. Data and annotations will be stored in the OvCa SPORE database and will be updated and retrieved for research projects following established HIPAA protocols. The TPC draws on resources already available through HCC, including the Cancer Center Support Grant (CCSG) cores and the Magee-Womens Research Institute and Foundation (MWRI). As such it efficiently and effectively provides and facilitates the testing of clinically derived data and biospecimens to support OvCa SPORE investigators, and the greater ovarian cancer research community, ultimately improving the lives of patients suffering from this devastating disease.