Spatial Molecular Imager for Translational Research

Abstract public domain (NIH RePORTER)

Project Summary/Abstract This proposal details a funding request for a commercially available NanoString Spatial Molecular Imaging (SMI) instrument, which is a single-cell imaging platform that enables investigation of intact tissues through the power of spatial multiomics. The instrument will be installed in the Translational and Correlative Studies Laboratory (TCSL), a Core Service Center that is overseen by the Center for Cellular Immunotherapies (CCI) at the Perelman School of Medicine of the University of Pennsylvania (PENN). The instrument will support NIH-funded research by investigators at PENN, collaborative research with NIH-funded researchers from across the U.S. (e.g., National Institute on Aging) where similar technology and expertise is not available, and the training of graduate students and postdoctoral fellows. The SMI instrument offers the ability to detect and quantify thousands of RNA and protein molecules at subcellular high-plex three-dimensional resolution using molecular digital “barcodes” from whole sections of formalin-fixed paraffin embedded (FFPE) biological samples. This extremely high sensitivity, resolution, and the multiplex nature of the information allows simultaneous profiling at both the protein and transcript level of large numbers of individual cells of interest while observing them in their spatial context in readily available fixed biopsies and histological sections. The analytical power of the SMI instrument for tissue samples thus exceeds the capabilities of flow cytometry and single-cell RNA sequencing that require dissociated cells, and traditional immunohistochemistry/in situ hybridization (IHC/ISH) approaches that are limited in the number of analytes that can be interrogated at one time. The ability of the CosMx SMI platform to bridge the gap between high plex, high throughput, and high resolution will transform the research of several PENN investigators; it will be utilized to elucidate and map cell types, generate cell atlases, analyze cell- cell interactions, and discover single-cell biomarkers. The research projects that will be advanced are broad in scope and all high-impact, including investigations of mesothelioma, prostate cancer, pancreatic cancer, lymphoma, glioblastoma, colorectal cancer, UV-induced skin cancer, acute myeloid leukemia, myelodysplastic syndromes, and Alzheimer’s disease. The technology sought is relatively new, with few such instruments available in the academic setting nationwide (since early 2019/2020) and is expected to impact a large group of intra- and extramural users. The instrument will be managed by the very experienced team in the TCSL within an already large and robust research environment.

Public health relevance public domain (NIH RePORTER)

Project Narrative This application requests support to purchase a Spatial Molecular Imaging instrument that can be used to probe slide-mounted preserved tissue sections for the presence of proteins and RNAs, generate high resolution images that show the specific locations of these molecules within individual cells. This information will allow the identification and characterization of infused therapeutic cells within the environment of tissue biopsies from patients treated for cancer and other diseases, thus guiding the development of new therapies.