PROJECT SUMMARY/ABSTRACT The Experimental Pathology Shared Resource (ExpPath) mission is to provide quality-controlled, consistent, reliable, and cost-effective services for the morphologic and molecular analyses of tissues impacted by cancer. ExpPath is crucial to the four Perlmutter Cancer Center (PCC) Research Programs, as it serves as a central hub in the workflow of tissue-based translational research and is uniquely positioned as a “bridge” between “wet- bench” research laboratories and the clinic. Ninety-seven (97) members from all four Programs used ExpPath services during the current funding period (2018-2022), and 124 cancer-related peer-reviewed grants included ExpPath services. ExpPath is directed by Cynthia Loomis, MD, PhD, an internationally recognized developmental biology and cancer researcher with >30 years' of experience in leading expertise-intensive resource laboratories focused on spatial analyses of normal and diseased tissues. She is assisted by a staff of 8 highly trained scientists, including 3 MDs/PhDs, and a New York state certified histotechnology technician. ExpPath provides standard and highly customized histopathologic services for pre-clinical tumor models and works closely with the Center for Biospecimen Research and Development (CBRD), which provides histopathologic services for CAP-certified, IRB-compliant human samples. ExpPath tests and optimizes state- of-the-art assays on human or animal tissues and has been at the forefront of emerging spatial profiling technologies. Over the past 5 years, ExpPath has significantly expanded its service portfolio of biomarker assays and image analysis. Current state-of-the-art technologies available to PCC members include multiplex RNAscope, high parameter immunostaining (PhenoCycler/CODEX), spatial transcriptomics (Visium and GeoMx), and neural network-based image analysis software and training (HALO). Implementation of these cutting-edge technologies requires diverse expertise, so ExpPath collaborates closely with CBRD, The Genome Technology Center (GTC), The Immune Monitoring Laboratory (IML), The Metabolomics Laboratory (MBX) and The Microscopy Core Laboratory (MICROS). ExpPath solicits yearly surveys and meets with its internal advisory board to ensure ongoing alignment with PCC investigator needs. It achieves its mission by means of four Specific Aims: 1) To assist PCC investigators in the molecular and morphologic characterization of normal and diseased tissues by providing relevant scientific expertise and technical support, 2) To train investigators in all aspects of tissue preparation, biomarker detection and analysis, and to facilitate rigor and reproducibility by standardizing procedures across the institution, 3) To introduce cutting-edge technology and integrate novel approaches for in situ interrogation of intact tissues and 4) To expedite translational research by clinical investigators and basic scientists with shared research interests by facilitating multi...