Human Skin Disease Resource-based Center

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 DESCRIPTION (provided by applicant): Mouse models have provided many biologic insights and remain the most popular system in which to conduct skin disease research. However there are significant differences between the skin and immune systems of mice and humans. These differences are incompletely characterized, making it difficult to know if observations made in mice will hold true in humans. 90% of the therapies that cure cancer in mice and all Staph. Aureus vaccines developed in mice have failed in human trials. Research carried out on human cells and tissues could address this knowledge gap but there have been many barriers to conducting high quality human research. The past five years have seen a revolution in the development of human biobanks and powerful new analytic techniques that make high-quality human skin disease research accessible. The goals of this Center are 1) to accelerate human skin disease research by providing researchers at any institution with access to human specimens and cutting edge analytic techniques and 2) to bring new investigators into the field of human skin disease research. The research community potentially includes any individual wishing to carry out human skin disease research; we have included 24 projects from investigators who wish to utilize Center services. The Center is composed of an Administrative Core and three Resource Cores. The Administrative Core manages and oversees all activities of the Center and administers Outreach activities, including grants to encourage human skin disease research, a Center Portal to disseminate human research resources and a biennial International Conference on Human Skin Disease. The Human Tissues Biobank Core provides access to over 23,000 highly characterized consented patients and over 1.5 million banked pathologic specimens, both searchable by diagnosis, as well as to fresh human skin, purified cell populations from human skin and immunodeficient mice grafted with human skin and blood. The Next Generation Immunoanalysis Core provides access to cutting-edge cytometry by time of flight (CyTOF), which can evaluate 45 different markers in a single sample with no signal overlap, and to high throughput TCR sequencing (HTS) which allows one step comprehensive profiling of T cells in tissues and the ability to identify and track pathogenic T cell clones. The Advanced Imaging & Nanostring Core provides access to tyramide-based six color immunostaining with spectral imaging and automated image analysis, which provides the equivalent of flow cytometry data on cell types in formalin fixed paraffin embedded (FFPE) tissue sections. This core also provides NanoString analyses, the first technique that provides accurate quantitative RNA and DNA analyses of up to 800 targets in FFPE biopsies. Taken together, these two techniques allow comprehensive protein and gene expression profiling for the first time in FFPE samples. In summary, our center will provide access to cutting-edge biobanks and technologies to any researcher at any institution who wishes to carry out skin disease research using human cells and tissues with the goal of accelerating human skin disease research.