Project Summary/Abstract: Next Generation Tissue Analysis & Imaging Core Research on human skin diseases has been hampered by limitations on the number of studies that can be carried out on small skin biopsy specimens and formalin-fixed, paraffin-embedded (FFPE) specimens. This core seeks to accelerate human skin disease research by providing access to three transformative techniques: six color immunostaining, with spectral imaging and automated cell analyses, NanoString-based RNA and DNA profiling and Digital Spatial Profiling. Taken together, these approaches allow comprehensive profiling of protein, RNA and DNA targets on small samples of skin and they work equally well on FFPE samples. Tyramide amplification based serial immunostaining allows six color labeling of FFPE specimens with no antibody species interference; multi spectral imaging on the Mantra imaging system provides image deconvolution and automated cell analyses, allowing identification and selective study of particular cell types within the section. NanoString profiling allows rapid, highly quantitative measurement of up to 800 DNA or RNA targets using minimal starting material and is the first gene expression technology to work equally well on FFPE samples. Digital Spatial Profiling utilizes RNA and protein probes with UV sensitive linkers to provide spatially resolved expression profiling of 10-1000s of protein or RNA targets in a section. The Core is led by renowned dermatopathologist Dr. Martin Mihm, who will provide consultative assistance to Center users to enhance their understanding of human skin disease. The research community can include any individual wishing to carry out translational human skin disease research. We have included projects from 28 investigators who wish to utilize the services of this Core. In summary, this Core provides access to cutting- edge tissue based analytic techniques that have the potential to significantly advance our understanding of human skin diseases.