Human Skin Disease Resource-based Center

 描述(由申请人提供)：小鼠模型提供了许多生物学见解，仍然是进行皮肤病研究的最受欢迎的系统。然而，老鼠和人类的皮肤和免疫系统之间存在着显着的差异。这些差异的特征并不完全，因此很难知道在老鼠身上所观察到的结果是否也适用于人类。在小鼠和所有金黄色葡萄球菌中治愈癌症的90%的疗法。在老鼠身上开发的金黄色葡萄球菌疫苗在人体试验中失败了。对人类细胞和组织进行的研究可以弥补这一知识鸿沟，但在进行高质量的人类研究方面存在许多障碍。在过去的五年里，人类生物库和强大的新分析技术的发展发生了一场革命，使高质量的人类皮肤病研究变得容易获得。该中心的目标是：1)通过向任何机构的研究人员提供获取人类样本和尖端分析技术的途径，加速人类皮肤病研究；2)将新的研究人员带入人类皮肤病研究领域。研究社区可能包括任何希望开展人类皮肤病研究的个人；我们已经包括了24个希望利用中心服务的研究人员的项目。该中心由一个管理核心和三个资源核心组成。行政核心管理和监督中心的所有活动，并管理外联活动，包括鼓励人类皮肤病研究的赠款、传播人类研究资源的中心门户网站和两年一次的人类皮肤病国际会议。人类组织生物库核心提供了超过23,000个高度特征化的同意患者和超过150万个可通过诊断进行搜索的库中病理标本，以及新鲜的人类皮肤、从人类皮肤中纯化的细胞群以及移植了人皮肤和血液的免疫缺陷小鼠。新一代免疫分析核心提供了尖端的飞行时间细胞仪(CyTOF)和高通量TCR测序(HTS)，前者可以在没有信号重叠的单个样本中评估45种不同的标记，后者允许一步全面分析组织中的T细胞，并能够识别和跟踪致病T细胞克隆。这个 高级成像和纳米串核心通过光谱成像和自动图像分析提供了基于酪胺的六色免疫染色，提供了相当于福尔马林固定石蜡包埋(FFPE)组织切片中细胞类型的流式细胞仪数据。该核心还提供纳米串分析，这是第一项提供FFPE活组织检查中多达800个目标的准确定量RNA和DNA分析的技术。综合起来，这两项技术首次允许在FFPE样本中进行全面的蛋白质和基因表达谱分析。总之，我们的中心将为任何机构的任何研究人员提供访问尖端生物库和技术的途径，这些研究人员希望使用人类细胞和组织进行皮肤病研究，目标是加速人类皮肤病研究。

 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.