Core A (Pathology Core) - Abstract/Summary The study of pancreatic ductal adenocarcinoma (PDAC) presents unique challenges given its formidably complex histopathology, the many diverse cell types of the tumor microenvirionment (TME), myriad genetic abnormalities and associated biological impact, and practical limitations of tissue availability and quality. Our pathology team, with its deep expertise in mouse and human PDAC, has played a central and essential role in the pathologic analysis of virtually all experiments of this P01 since its inception. Broadly speaking, these activities include evaluation of genetically engineered mice (GEM), including mice with temporally regulated, compartment-specific disruption in epithelial and / or stromal components; analyses of tumor promoting signaling pathways with cell-type specific localization to either neoplastic cells per se, or within the host response in the TME; identification and multi-dimensional assessments of cellular components within the TME; and the cross- species validation of observations between GEM models and human tumor samples. The Pathology Core will continue to collect, maintain, archive and record all human and mouse PDAC-associated biological resources. These materials include organoids created from primary and metastatic human and mouse PDAC, and a repository of annotated low-passage PDAC cell lines. Core A will work in close collaboration with the Project Investigators to achieve three specific aims: i) to provide histology services and consultative expertise, including centralized review in the pathologic evaluation of mouse and human pancreatic neoplasms; ii) to provide infrastructure and technical expertise for a variety of immunohistochemical, immunofluorescent and in situ hybridization assays with quantitative image analysis; and iii) to generate, characterize and maintain organoid models, as well as early passage tumor and stromal cells cultures for use by the Projects as well as for allele engineering in The Modeling & Experimental Therapeutics Core. A testament to this Core’s progress stems from the creation of >165 PDXs and >30 low passage PDAC cell lines during the previous cycle. Core A’s leader is Dr. Huamin Wang at MDACC, joined by Co-Investigators Drs. Anirban Maitra and Michael Kim- bring long- standing expertise, numerous P01 collaborations and a strong publication record in the histopathological and molecular assessment of human and murine PDAC tissues. Core A will build upon the strong foundation of prior and many ongoing interactions between investigators in order to facilitate a highly successful P01 outcome.