University of Michigan Skin Biology and Diseases Resource-based Center

密歇根大学皮肤生物学和疾病资源中心

• 批准号: 10643961
• 负责人: Johann Eli Gudjonsson
• 金额: $ 73.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10643961
• 关键词: Acceleration; Address; Advisory Committees; Animal Model; Area; Award; Basic Science; Big Data; Bioinformatics; Biological; Biology; Biomedical Research; Breeding; Budgets; CRISPR/Cas technology; Cell Culture Techniques; Communication; Communities; Cutaneous; Data; Data Analyses; Data Set; Derivation procedure; Development; Disease; Disease model; Effectiveness; Ensure; Evaluation; Experimental Designs; Fees; Fibrosis; Fostering; Genetically Engineered Mouse; Genomics; Goals; Grant; Hair follicle structure; Human; Immunology; Inflammation; Inflammatory; Infrastructure; Institution; Knowledge; Leadership; Mentors; Methods; Michigan; Mission; Modeling; Mutagenesis; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Neoplasms; Patients; Periodicals; Personnel Management; Phenotype; Primary Cell Cultures; Production; Productivity; Protocols documentation; Quality Control; Research; Research Infrastructure; Research Personnel; Resources; Series; Services; Skin; Speed; Structure; Study models; Surveys; Systems Biology; Training; Transgenes; Translating; Translational Research; Travel; Universities; Validation; Visit; Work; bioinformatics resource; clinically relevant; data analysis pipeline; design; epigenomic profiling; established cell line; experience; experimental analysis; gene induction; genome editing; genomic data; immune function; in silico; in vivo; innovation; insight; keratinocyte; knockout gene; member; mouse model; operation; outreach; programs; satisfaction; screening; service delivery; skin disorder; symposium; training opportunity; transcriptomic profiling; transcriptomics; translational impact; ultraviolet irradiation; web based interface

PROJECT SUMMARY - OVERALL The overall goal of the University of Michigan Skin Biology and Diseases Resource-based Center (UM- SBDRC) is to leverage our strengths in genomic editing, bioinformatics and mouse modelling to enable rapid transition from discovery to function, address biological and disease context, and facilitate development of appropriate state-of-the-art in silico approaches and in vivo mouse models of disease. A major emphasis of the UM-SBDRC is to apply years of cutting-edge mouse modeling expertise to the study of inflammatory skin disease using new knowledge gained through big-data approaches. Thus, the UM-SBDRC will both facilitate and accelerate ongoing research towards new discoveries and ultimately benefit a wide range of patients with cutaneous disorders. Two Resource Cores will be established within the UM-SBDRC: they will enhance efficiency and translational impact of cutaneous research; provide access to unique resources and expertise; facilitate new discoveries; and provide training and guidance regarding experimental design and analysis. In addition, the Resource Cores will continuously innovate to maintain our research at the forefront of the field. The Functional Analytics Core will provide unique and innovative, state-of-the art services for CRISPR/Cas9 mutagenesis in keratinocytes, with transcriptomic and epigenomic profiling of genetically-altered keratinocytes, and integration into a systems biology pipeline for data analysis and interpretation. This core will also provide UM-SBDRC members direct access to our bioinformatics resources and to large-scale genomic and transcriptomic datasets of human skin disease through a searchable web-based interface. The Animal Modeling Core will provide services for the design, development, validation, and characterization of genetically-engineered mouse models (GEMMs) to aid in the functional validation of results generated in the Functional Analytics Core. The Animal Modeling Core will also provide resources and guidance for GEMM phenotyping and in vivo manipulation, including transgene induction protocols, UV irradiation, inflammation and fibrosis models, and for establishment of cell cultures from GEMMs. The Administrative Core will provide leadership, oversight and structure for the UM-SBDRC and build and administer a robust Enrichment Program, which includes a Mentoring Program, Pilot & Feasibility Program, Travel Awards, Visiting Speaker Series, and an Annual Symposium, with strong institutional and departmental support for the Center. In summary, UM-SBDRC will provide sophisticated infrastructure and state-of-the-art resources, expertise, and training opportunities at Michigan. This new Center is in line with the NIAMS mission to provide critical research infrastructure, pooled facilities, services and resources to groups of investigators conducting research on skin biology and diseases. The UM-SBDRC will enrich and enhance effectiveness of ongoing basic and translational research, help bring outside investigators into the field of cutaneous biology, broaden the scope of skin research, and accelerate new discoveries to ultimately benefit patients with a wide range of skin diseases.

项目摘要 - 总体 密歇根大学皮肤生物学和疾病的总体目标基于资源的中心（UM- SBDRC）是利用我们在基因组编辑，生物信息学和小鼠建模方面的优势来快速 从发现过渡到功能，解决生物学和疾病环境，并促进发展 适当的硅方法和体内小鼠疾病模型中的适当最先进。重点 UM-SBDRC是将多年的尖端小鼠建模专业知识应用于炎症皮肤的研究 使用大数据方法获得的新知识疾病。因此，UM-SBDRC都将有助于 并加速对新发现的正在进行的研究，并最终使许多患者受益 皮肤疾病。 UM-SBDRC将建立两个资源核心：它们将增强 皮肤研究的效率和翻译影响；提供独特的资源和专业知识； 促进新发现；并提供有关实验设计和分析的培训和指导。在 此外，资源核心将不断创新，以将我们的研究保持在该领域的最前沿。 功能分析核心将为CRISPR/CAS9提供独特而创新的最先进的服务 角质形成细胞中的诱变，具有遗传变化角质形成细胞的转录组和表观基因组分析 并集成到系统生物学管道中，以进行数据分析和解释。这个核心也将提供 UM-SBDRC成员可以直接访问我们的生物信息学资源以及大规模的基因组和 通过可搜索的基于Web的界面，人类皮肤病的转录组数据集。动物 建模核心将为设计，开发，验证和表征提供服务 遗传工程的小鼠模型（GEMM）有助于对在该中产生的结果的功能验证 功能分析核心。动物建模核心还将为GEMM提供资源和指导 表型和体内操作，包括转基因诱导方案，紫外线照射，炎症和 纤维化模型，以及从宝石中建立细胞培养物。行政核心将提供 UM-SBDRC的领导，监督和结构，并建立和管理强大的丰富 计划，包括指导计划，飞行员和可行性计划，旅行奖，访问者 系列和年度研讨会，对该中心有强有力的机构和部门支持。在 摘要，UM-SBDRC将提供复杂的基础架构和最先进的资源，专业知识和 密歇根州的培训机会。这个新中心与Niams的任务一致，以提供关键 研究基础架构，合并设施，服务和资源向进行研究的研究人员 关于皮肤生物学和疾病。 UM-SBDRC将丰富并提高持续基本和 翻译研究，帮助外部研究人员进入皮肤生物学领域，扩大了范围 皮肤研究并加速新发现，最终使患有多种皮肤疾病的患者受益。

项目成果

Skin-Expressing lncRNAs in Inflammatory Responses.

• DOI: 10.3389/fgene.2022.835740
• 发表时间: 2022
• 期刊: Frontiers in genetics
• 影响因子: 3.7

Pathophysiology of generalized pustular psoriasis.

全身性脓疱型银屑病的病理生理学。

• DOI: 10.1111/exd.14768
• 发表时间: 2023
• 期刊: Experimental dermatology
• 影响因子: 3.6
• 作者: Young,KellyZ;Sarkar,MrinalK;Gudjonsson,JohannE
• 通讯作者: Gudjonsson,JohannE

Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation.

• DOI: 10.1016/j.isci.2022.104669
• 发表时间: 2022-07-15
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Kim, Seok-Jo;Bale, Swarna;Verma, Priyanka;Wan, Qianqian;Ma, Feiyang;Gudjonsson, Johann E.;Hazen, Stanley L.;Harms, Paul W.;Tsou, Pei-Suen;Khanna, Dinesh;Tsoi, Lam C.;Gupta, Nilaksh;Ho, Karen J.;Varga, John
• 通讯作者: Varga, John

The Psoriasis Glycome: Differential Expression of Cholesterol Particle Glycans and IgA Glycans Linked to Disease Severity.

牛皮癣糖类：胆固醇颗粒聚糖和 IgA 聚糖的差异表达与疾病严重程度相关。

• DOI: 10.1016/j.jid.2022.03.030
• 发表时间: 2022
• 期刊: The Journal of investigative dermatology
• 作者: Maverakis,Emanual;Liakos,William;Park,Dayoung;Patel,Forum;Siddiqui,Fariha;Kailemia,MuchenaJ;Ruhaak,LRenee;Marusina,AlinaI;Luxardi,Guillaume;Gudjonsson,JohannE;Le,StephanieT;Armstrong,AprilW;Liao,Wilson;Merleev,AlexanderA

Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab.

结节性痒疹的单细胞分析表明免疫基质串扰驱动促纤维化反应并用奈莫利珠单抗逆转。

• DOI: 10.1016/j.jaci.2023.07.005
• 发表时间: 2024
• 期刊: The Journal of allergy and clinical immunology
• 作者: Ma,Feiyang;Gharaee-Kermani,Mehrnaz;Tsoi,LamC;Plazyo,Olesya;Chaskar,Prasad;Harms,Paul;Patrick,MatthewT;Xing,Xianying;Hile,Grace;Piketty,Christophe;Lazzari,Anne;VanDelm,Wouter;Maverakis,Emanual;Nakamura,Mio;Modlin,RobertL;K
• 通讯作者: K