Resource Core B - Modeling of skin disease for mechanistic analysis and therapeutic discovery

资源核心 B - 用于机制分析和治疗发现的皮肤病建模

基本信息

批准号：
10676785
负责人：
Michael Rendl
金额：
$ 15.69万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10676785
关键词：
Archives Biological Process Biology CRISPR interference CRISPR-mediated transcriptional activation CRISPR/Cas technology Candidate Disease Gene Cell Separation Cell model Cell physiology Cells Clinical Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Collection Consult Consultations Derivation procedure Dermal Dermatopathology Disease Disease model Environment Fibroblasts Fluorescence-Activated Cell Sorting Functional disorder Gene Expression Generations Genes Genetic Genetic Skin Diseases Genetic Transcription Genetic study Genomics Goals Grant Habitats Hair follicle structure Histopathology Homeostasis Human Human Genetics Image Imaging technology Immune Improve Access In Vitro Institution Leadership Merkel Cells Modeling Molecular Analysis Multiplexed Ion Beam Imaging Mus Patients Physiological Population Production Proteins Protocols documentation Research Research Infrastructure Research Personnel Resources Retrieval Sampling Scholarship Services Skin Skin Physiology Skin Tissue Slide Stains Surgeon Technical Expertise Technology Therapeutic Training cell behavior cellular imaging comparative cost epidermal stem cell ex vivo imaging fluorescence imaging gene correction genetic analysis genome editing human disease human imaging human model imaging biomarker in vivo induced pluripotent stem cell induced pluripotent stem cell technology interest keratinocyte melanocyte mouse genetics mouse model multiplexed imaging mutant operation overexpression protein biomarkers sample archive skin barrier skin disorder skin organogenesis therapeutic evaluation therapeutic target tongue papilla virtual

项目摘要

Summary – Resource Core B Many technical, logistical and cost barriers hinder efficient and feasible access to high-end experimental approaches in skin research. Efforts by Core B, “Modeling of skin disease for mechanistic analysis and therapeutic discovery” will systematically overcome these barriers for skin researchers by facilitating access to human skin samples, harnessing our expertise in generating and analyzing sophisticated mouse genetic and human iPSC-derived models of skin disease, and providing a streamlined interface with Core C for genomics and transcriptional analyses. In parallel, the entry barriers to skin biology and diseases research will be lowered by providing Pilot Grants to junior investigators and researchers newly entering the skin biology and diseases field, and the costs of high-end technologies will be defrayed by User Scholarships. Core B will offer users specialized technical, clinical and scientific know-how and services in advanced skin research as well as critical research infrastructure by providing A) clinical and histopathological expertise for easy retrieval of normal and diseased human skin and access to efficient multiplexed skin marker analysis for physiological and skin disease studies; B) scientific expertise and service for physiological studies of fundamental skin functions with advanced genetic mouse models and cell isolation and imaging technologies; and C) scientific expertise and service for human skin disease modeling with patient-derived iPSC technology and with CRISPR-based gene editing and expression manipulation for mechanistic analysis and therapeutic target discovery. These goals will specifically be achieved by 1) providing samples from our vast collection of archived normal and diseased human skin; 2) facilitating access to de-identified fresh human skin samples; 3) advanced multiplexed immunohistochemical imaging of marker proteins; 4) aiding in the generation of state-of-the-art genetic mouse models for skin functional studies; 5) providing training in refined isolation technologies for specific skin cell populations; 5) providing training for advanced live imaging in vitro and in vivo; 6) generating patient iPSCs and differentiating them to skin cells to model human skin disease; and 7) studying candidate skin disease genes by generating isogenic mutant and control iPSC-derived skin cells and through Cas9-based gene expression manipulation.

摘要 – 资源核心 B 许多技术、后勤和成本障碍阻碍了高效、可行地获得高端实验核心 B 的努力，“皮肤病建模以进行机械分析和 “发现”最终将通过促进皮肤研究人员获得这些治疗障碍来克服这些障碍人类皮肤样本，利用我们在生成和分析复杂的小鼠遗传和人类 iPSC 衍生的皮肤病模型，并为基因组学提供与 Core C 的简化界面与此同时，皮肤生物学和疾病研究的进入壁垒将是。通过向新进入皮肤生物学领域的初级研究人员和研究人员提供试点资助来降低田间疾病和高端技术的费用将由用户核心 B 提供的奖学金支付。用户在高级皮肤研究以及关键的研究基础设施，通过提供 A) 临床和组织病理学专业知识，以便轻松检索正常和患病的人类皮肤，并获得有效的多重皮肤标记分析，以进行生理和皮肤病研究；B) 基本皮肤功能生理研究的科学专业知识和服务拥有先进的基因小鼠模型和细胞分离和成像技术；以及 C) 科学专业知识；使用源自患者的 iPSC 技术和基于 CRISPR 的人类皮肤病建模和服务用于机制分析和治疗靶点发现的基因编辑和表达操作。具体通过以下方式实现目标：1) 从我们大量存档的正常和患病的人类皮肤；2) 方便获取未识别的新鲜人类皮肤样本；3) 先进的多重分析标记蛋白的免疫组织化学成像；4) 帮助产生最先进的基因小鼠皮肤功能研究模型；5）提供针对特定皮肤细胞的精细分离技术的培训人群；5) 提供先进的体外和体内实时成像培训；6) 生成患者 iPSC 和将它们分化为皮肤细胞以模拟人类皮肤病；7) 研究候选皮肤病基因；通过产生同基因突变体并控制 iPSC 衍生的皮肤细胞以及通过基于 Cas9 的基因表达操纵。