PROJECT SUMMARY (MPIC) The Molecular Pathology and Imaging Core (MPIC) is a unique entity at the University of Pennsylvania and provides tremendous service, resources, expertise, and efficiency for investigators of the Center for Molecular Studies in Digestive and Liver Diseases (CMSDLD). MPIC has specific expertise in the processing and analysis of all tissues and cells, including gastrointestinal organoids, that are relevant to CMSDLD investigators and houses specialized microscopes, reagents, and equipment essential for the research of CMSDLD investigators; no resource with similar expertise exists on the Penn campus or in nearby institutions. In addition, by providing cost-effective approaches, MPIC is particularly beneficial to Pilot and Feasibility awardees, who receive subsidies for MPIC services, and junior investigators/Associate Members, many of whom do not yet have independent funding. Established in 1995 as part of a Program Project grant, MPIC expanded in 1997 to serve CMSDLD investigators and, since its inception, has been heavily utilized and extremely successful, serving as a model core facility for numerous other Centers and Program Projects at the University of Pennsylvania and throughout the country. MPIC is a key component of the CMSDLD, providing essential, routine services as well as cutting edge technologies to CMSDLD investigators. Currently comprising more than 1,000 square feet on the 9th floor of BRBII/III, MPIC is led by an experienced Director, a highly-trained Technical Director, and skilled and knowledgeable staff. By integrating with the other CMSDLD Cores, as well as other cores and resources on campus such as Next-Generation Sequencing Core and central Tier 1 Microscopy Core of the Perelman School of Medicine and the expert pathologists of the Comparative Pathology Core at the University of Pennsylvania School of Veterinary Medicine, MPIC dramatically expands the services available to CMSDLD investigators. Notably, since the last competitive renewal of this application, MPIC has incorporated and integrated new services and technologies, including Visium Spatial Transcriptomics and automated RNAscope on the core’s Leica Bond RXm autostainer. Additionally, MPIC promotes new collaborations and research directions among its users. Overall, MPIC serves the CMSDLD by pursuing the following two interrelated Specific Aims: (1) To enhance the efficiency and productivity of CMSDLD investigators by providing specialized technical resources, services, and expertise in histology, pathology, and histologic imaging of the digestive tract, liver, and pancreas; and (2) To integrate new technologies that advance research and discovery for studies of digestive, liver, and pancreatic diseases by both surveying and anticipating the needs of CMSDLD investigators. As such, MPIC provides exceptional utility, quality, value, experience, service, and commitment to the CMSDLD.