Technological advances have now greatly expanded the frontier of single cell transcriptomics. We can now measure individual cells within their spatial context and directly observe cell-cell interactions. A leading technology in this area, named MERFISH, uses digital barcoding of mRNAs in the cell to measure gene expression at sub-cellular resolution. We propose to request the MERSCOPE instrument, which allows for MERFISH processing of hundreds of genes on tumor and tissue sections to advance our studies of cancer and other diseases that affect Veterans’ health. In situ hybridization (ISH)-based methods entail a process whereby a target sequence is detected by hybridization of a complementary fluorescent probe. The addition of sequential rounds of hybridization and imaging combined with barcoding have enabled substantial multiplexing. In multiplexed error-robust fluorescence ISH (MERFISH), successive rounds of hybridizations are imaged to detect the presence or absence of fluorescently labelled probes. The serial images are then decoded, using the error-robust barcode associated with each transcript identity. MERFISH has been used over a wide range of scales, from transcript location within individual cells to tissue-level spatial transcriptomics. Research projects advancing studies of diseases highly relevant to the Veterans’ community that will be supported by this instrument include studies focusing on cancers such as prostate and lung cancer, brain diseases, such as traumatic brain injury (TBI), frontotemporal dementia (FTD), and lung diseases. Spatial transcriptomics is required to simultaneously image multiple cells in affected tissues to determine cellular localization and gene expression. Lung transplant and pulmonary fibrosis studies will be served by this equipment to image specific cell types in lung transplant and fibrotic tissues. Infectious disease research projects related to HIV and SARS-CoV-2 will be able to utilize this instrument to better understand the pathogenic mechanisms of infection and persistence in tissues. Studies of prostate, hepatocellular, and lung cancer will also utilize this equipment to characterize prognostic biomarkers and understand the tumor microenvironment. We are excited to request the MERSCOPE, a state-of-the-art spatial transcriptomics instrument that will provide innovative and outstanding images for research studies to advance Veterans’ health. We anticipate the MERSCOPE to provide services essential towards accomplishing VA’s research goals to understand and treat diseases of high importance to the Veteran population.