PROJECT SUMMARY The Biospecimen and Reagents Core [BRC] provides high quality annotated specimens and expert pathology consultation to enhance the P01 projects. The BR&C CWRU and Duke components have long track records of supporting multi-investigator basic, translational and clinical research relating to multiple aspects of the Barrett's Esophagus [BE] and BE- neoplasia. The BRC is co-lead by two nationally recognized gastrointestinal pathologists with expertise in esophageal pathology who have well established track records in tissue-based translational research. The BRC co-leaders have worked together for many years and have longstanding collaborations with the P01 teams. The BRC components have differencing and complementary resources. Both the CWRU and the Duke components have large bioarchives which have been used to support multiple large scale NIH funded projects for over 20+ years. The BR&C has tissue and blood biospecimens from over 6,200 patients suitable for this P01. The BR&C leverages the Case CCC Shared Resources, the UH Pathology Translational Research Core and the Duke BioRepository & Precision Pathology Center shared resource to maximize efficiencies, utilize their expertise and advanced technologies. For Project 1 the BRC was integral to the discovery of germline abnormalities of VSIG10L as a predisposing factor in some patients with Familial Barrett's Esophagus. The BRC worked with Prj 1 to define the knock in and knock out mouse models which form the basis of this project and identified a multilayer epithelium complex in Prj 1 murine models – recognized as a robust marker of BE changes and linked to BE in humans. For Project 2 the BRC and collaborators developed the novel approach of using pigs as a model for esophageal injury – including the study of esophageal submucosal glands [ESMGs] as a potential site of origin of BE. Inspired by this effort, Prj 2 and the BRC identified and provided sections of ESMGs during screening of multiple esophagectomies and then worked with Prj 2 to immunoprofile the ESMGs. The molecular mechanisms identified formed the basis for the project. For Project 3 the BRC supplied high quality tissue samples and immunohistochemistry expertise in the investigation of EPHB2 signaling in esophageal carcinogenesis used to define potential pathways of development of BE – results of which formed the basis for the project. The BRC, with Core C, will continue to provide support to the P01 investigators and will enhance their projects by supplying quality controlled esophagus tissues, human and animal pathology expertise and facilitate state of the art tissue diagnostics including immunohistochemistry, ISH, tissue microdissection, spatial transcriptomics and single cell sequencing.