ShEEP Request for Imaging Mass Cytometry

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The goal of this proposal is to install and integrate the Fluidigm Hyperion Imaging Mass Cytometer (IMC) system in the Cellular and Molecular Evaluation Core (CMEC) Facility within Research Service at the Ralph H. Johnson (RHJ) VA Medical Center. The overarching objective of this core facility is to provide tools and services, including immunohistochemical, flow cytometry, and cell sorting applications, necessary to support and advance research that directly impacts the health of our Veterans. Conventional immunohistochemical (IHC) approaches have been historically limited to the simultaneous detection of only a few markers (~8). Traditional flow cytometry, while allowing for multiparameter analysis, does not allow for spatial analysis of cellular or subcellular marker expression within a tissue. In contrast, time of flight mass cytometry (CyTOF) allows for the simultaneous detection of 40+ markers on one single cell. By combining the existing high dimensional Helios mass cytometer CyTOF platform with the Hyperion laser ablation system, we are able to bring this powerful detection method, termed imaging mass cytometry (IMC), into tissues. The central hypothesis addressed by this core is that the high dimensional analysis Hyperion IMC system will allow VA researchers to use small fixed tissue samples to examine complex subcellular, cellular, and cell-matrix interactions in the intact tissue microenvironment and provide a technology bridge to existing transcriptomic and imaging methods to understand pathologies impacting our Veterans. Our investigators have identified four primary aims that will be accomplished through this groundbreaking technology that provides high throughput, high-dimensional quantitative analyses in situ of complex cellular samples: 1) Identify novel cell types and their cellular and sub-cellular proteins that contribute to the pathology of disease; 2) Uncover new intracellular, cell- cell, and cell-ECM interactions important for disease progression; 3) Examine rare events (including stem cells) in physiological and pathological conditions; and 4) Discover novel biomarkers of disease and/or clinical response to treatment, enhancing the development of targeted, personalized, precision therapies. The state-of-the-art technology afforded by the Hyperion IMC System is broadly applicable across the diverse animal- and human-based research efforts of our local VAMC investigators including studies in traumatic brain injury, stroke, spinal cord injury, respiratory illness, cardiovascular disease, immunology, oncology, orthopedic injury, Alzheimer’s disease, and mental health disorders. This technology does not currently exist at RHJ VAMC, the Affiliate (Medical University of South Carolina, MUSC), or in the state. Based on the number of interested investigators and diverse disease-related applications, we believe that this upgrade will meet demands of investigators for cutting edge technologies to advance translational medicine and allow the VA CMEC to provide the next generation of mass cytometry capabilities. This expansion will position VA as a leader in integration of mass cytometry into clinical trials, personalized disease treatments, and development of novel therapies. Incorporating the Hyperion Imaging Mass Cytometer System into the established CMEC will greatly strengthen the research capabilities of our station (and those in the VISN), facilitating basic scientific discovery of mechanisms underlying physiological and pathological processes and translation of these findings to support the rapid implementation of cutting-edge personalized medical treatment to improve quality healthcare for our Nation’s Veterans.