Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT)

狼疮组学皮肤肾研究小组 (LOCKIT)

• 批准号: 10452169
• 负责人: Jill P Buyon
• 金额: $ 105.37万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-21 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10452169
• 关键词: Acute; Adaptive Immune System; Address; Autoimmune; Autoimmune Diseases; B-Cell Activation; B-Lymphocytes; Beds; Biological; Biology; Biopsy; Blood; California; Cause of Death; Cells; Chronic; Clinical; Collection; Communities; Consent; Country; Cutaneous; Data; Data Set; Databases; Dermatologist; Disease; Dissociation; Elements; Endothelial Cells; Enrollment; Ethnic Origin; Exanthema; Fibroblasts; Genetic; Goals; Heterogeneity; High Prevalence; Hospitals; Immune; Immunologics; Informed Consent; Institutional Review Boards; Interferon Type I; Intervention; Investigation; Kidney; Kidney Diseases; Lead; Liquid substance; Lupus; Lupus Nephritis; Mediating; Medicine; Michigan; Molecular; Monitor; Ohio; Organ; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pennsylvania; Periodicity; Peripheral; Phase; Phenotype; Pilot Projects; Population; Prevalence; Proteinuria; Proteomics; Protocols documentation; Publishing; Race; Recurrent disease; Registries; Regulation; Research Personnel; Research Priority; Rheumatology; Risk; Salivary Glands; Sampling; San Francisco; Severities; Site; Skin; Socioeconomic Status; Specimen; Speed; Synovial Membrane; Systemic Lupus Erythematosus; Systems Biology; Technical Expertise; Technology; Texas; Therapeutic; Time; Tissue Preservation; Tissues; Tubular formation; Underrepresented Minority; Universities; Urine; Woman; base; biological specimen archives; black women; cell preparation; clinical infrastructure; clinical phenotype; clinically actionable; cohort; college; data pipeline; design; digital imaging; disease phenotype; flexibility; image archival system; lupus cutaneous; medical schools; men; monocyte; multi-ethnic; multidisciplinary; next generation; novel; phenotypic data; programs; racial population; recruit; response; scale up; skin disorder; success; transcriptomics; translational applications; treatment response; working group; young woman

As the pace of discovery in the biology, genetics, and environmental regulation of SLE accelerates, the speed and efficiency of translational application assumes even greater importance. There is now unprecedented opportunity to harness technological advances to de-and reconstruct the enormity of phenotypic and immunologic heterogeneity in this prototypic autoimmune disease. Building on our clinical infrastructure and technical protocols that yielded high-quality tissue, urine and peripheral cells for transcriptomic and proteomic analyses in AMP1, an expanded team of multi-disciplinary investigators together form the Lupus Omics Cutaneous Kidney Investigation Team (LOCKIT) in response to the FOA: Accelerating Medicine Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) Program. Collective team discussions aligned the most significant scientific opportunities with clinical needs to focus on the kidney and skin, each with its own challenging heterogeneity. Understanding the molecular underpins of both very early kidney disease (with comparisons to data on established/relapsed disease generated in AMP1) and treatment inadequacies overall were considered high priority goals in the field, as were differentiating acute from chronic cutaneous disease and monitoring differences in treatment responses in these skin disease subsets. Availability of tissues to other teams will be complementary as biology is compared across diseases. Replicating successes of AMP1, LOCKIT will be led by the co-chairs of AMP1 SLE Clinical Working Group, Jill Buyon, NYU School of Medicine and Michelle Petri, Johns Hopkins University. They are joined by nephrologist Brad Rovin, Ohio State University, and dermatologist Victoria Werth, University of Pennsylvania, each recognized for translational contributions to SLE. To accomplish our directives and assure sufficient representation of underrepresented minorities among patients, included are three high-recruiting AMP1 sites led by Anna Broder, Albert Einstein College of Medicine; Maria Dall’Era, University of California San Francisco; and Jennifer Anolik, University of Rochester (co-chair of AMP1 and PI of RA site, adding B cell expertise). Two new sites, led by Karen Costenbader, Brigham and Women’s Hospital, and Ben Chong, University of Texas, Southwestern, bring expertise in patient outcomes and cutaneous lupus, respectively. All collaborate and publish together with cohorts collectively totaling 5,541 patients consenting to registries, and archived specimens including 98,980 longitudinal blood derivatives, and 3,311 kidney and 715 skin biopsies. To uniformly anchor discoveries, as in AMP1, Jeff Hodgin, University of Michigan will lead a digital imaging repository. LOCKIT is poised to apply state-of-the-art technologies and next generation analytics provided by scientific partnership with AMP AIM Cores to interrogate tissues and biologic fluids from informative populations. Although focusing on the kidney and skin, our cohorts include all SLE manifestations, providing agility to address other organs as AMP AIM evolves. LOCKIT commits to harmonize and optimize all aspects of the data pipeline, from collection to analysis, interpretation and dissemination.

随着SLE的生物学、遗传学和环境调控研究的步伐加快， 并且翻译应用的效率变得更加重要。现在有前所未有的 利用技术进步来消除和重建表型和基因突变的严重性的机会 这种典型自身免疫性疾病的免疫异质性。建立在我们的临床基础设施和 技术协议，产生高质量的组织，尿液和外周细胞的转录和蛋白质组学 AMP 1中的分析，一个由多学科研究人员组成的扩展团队共同组成了狼疮组学 皮肤肾研究小组（LOCKIT）响应FOA：加速医学合作伙伴关系 自身免疫和免疫介导的疾病（AMP AIM）计划。集体小组讨论使 最重要的科学机会与临床需要集中在肾脏和皮肤，每一个都有自己的 挑战异质性。了解极早期肾脏疾病（与 与AMP 1）中生成的已确诊/复发疾病数据和总体治疗不足的比较 被认为是该领域的高优先级目标，区分急性和慢性皮肤病也是如此， 监测这些皮肤病亚群中治疗反应的差异。其他团队的组织可用性 将是互补的，因为生物学是在疾病之间进行比较的。复制AMP 1的成功，LOCKIT将 由AMP 1 SLE临床工作组联合主席Jill Buyon、纽约大学医学院和Michelle领导 佩特里，约翰霍普金斯大学。俄亥俄州州立大学的肾病学家布拉德·罗文也加入了他们的行列， 皮肤科医生维多利亚沃思，宾夕法尼亚大学，每个承认的翻译贡献系统性红斑狼疮。 为了完成我们的指示，并确保代表性不足的少数民族在 患者，包括三个高招募AMP 1网站由安娜布罗德，阿尔伯特爱因斯坦医学院; Maria Dall'Era，加州大学弗朗西斯科分校; Jennifer Anolik，罗切斯特大学（ RA研究中心的AMP 1和PI，增加B细胞专业知识）。两个新的网站，由卡伦Costenbader，布里格姆和 妇女医院和得克萨斯大学西南分校的Ben Chong带来了患者预后方面的专业知识， 皮肤狼疮。所有人都与同龄人合作并共同发表，总计5，541人 同意登记的患者，以及包括98，980份纵向血液衍生物在内的存档标本，以及 3,311例肾脏和715例皮肤活检。为了统一锚的发现，如在AMP 1，杰夫霍金，大学 密歇根州将领导一个数字成像库。LOCKIT准备应用最先进的技术， 与AMP AIM Cores的科学合作伙伴关系提供的一代分析， 从信息丰富的人群中提取液体。虽然重点是肾脏和皮肤，但我们的队列包括所有SLE 表现，提供灵活性，以解决其他器官作为AMP AIM的发展。LOCKIT致力于协调 并优化数据管道的所有方面，从收集到分析、解释和传播。