Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT)

狼疮组学皮肤肾研究小组 (LOCKIT)

• 批准号: 10596281
• 负责人: Jill P Buyon
• 金额: $ 160万
• 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/10596281
• 关键词: Acceleration; 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; Collaborations; Collection; Communities; Consent; Country; Cutaneous; Data; Data Set; Databases; Dermatologist; Disease; Dissociation; Early identification; Elements; Endothelial Cells; Enrollment; Ethnic Origin; Exanthema; Fibroblasts; Genetic; Goals; Heterogeneity; High Prevalence; Hospitals; Immune; Immunologics; Informed Consent; Innate Immune System; 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; Periodicals; 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; Tissue Preservation; Tissue Procurements; Tissues; Tubular formation; Underrepresented Minority; Universities; Urine; Woman; Writing; biological specimen archives; black women; cell preparation; clinical infrastructure; clinical phenotype; clinically actionable; cohort; college; data pipeline; design; digital imaging; disease classification; disease phenotype; flexibility; image archival system; lupus cutaneous; medical schools; men; monocyte; multi-ethnic; multidisciplinary; next generation; novel; phenotypic data; programs; prototype; 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.

随着发现SLE的生物学，遗传学和环境调节的发现空间，速度 翻译应用的效率更为重要。现在有前所未有的 利用技术进步的机会，重建表型和 这种原型自身免疫性疾病中的免疫异质性。在我们的临床基础设施和 产生转录组和蛋白质组学的高质量组织，尿液和周围细胞的技术方案 AMP1的分析，一个扩展的多学科研究人员团队共同组成了狼疮的OMICS 皮肤肾脏调查小组（Lockit）回应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。集体团队讨论使 临床需要最重要的科学机会，需要专注于肾脏和皮肤，每种都有自己的 具有挑战性的异质性。了解两种早期肾脏疾病的分子基础（有 比较AMP1中产生的已建立疾病的数据和整体治疗不足 被认为是该领域的高优先目标，以及与慢性皮肤病和 监测这些皮肤病子集中治疗反应的差异。向其他团队提供组织的可用性 将在跨疾病中比较生物学时完成。复制AMP1的成功，Lockit将会 由AMP1 SLE临床工作组的联合主席，纽约大学医学院和米歇尔 彼得里，约翰·霍普金斯大学。肾脏科医生布拉德·罗文（Brad Rovin），俄亥俄州立大学和 皮肤科医生维多利亚·沃斯（Victoria Werth），宾夕法尼亚大学，每个人都因对SLE的翻译贡献而认可。 完成我们的指示并确保足够代表人数不足的少数民族 患者包括三个由阿尔伯特·爱因斯坦医学院的安娜·布罗德（Anna Broder）领导的三个高级招募AMP1站点； 玛丽亚·达尔拉（Maria Dall’era），加利福尼亚大学旧金山分校；罗切斯特大学的詹妮弗·阿诺利克（Jennifer Anolik）（联合主席 RA站点的AMP1和PI，增加了B细胞专业知识）。由Karen Costenbader，Brigham和 妇女医院和德克萨斯大学西南大学的本宗带来了患者预后的专业知识 皮肤狼疮分别。所有人都与共同总共5,541共同合作和发布 同意注册机构的患者以及包括98,980个纵向血衍生物的归档标本，以及 3,311肾脏和715个皮肤活检。像AMP1一样，统一的锚定发现 密歇根州将领导数字成像存储库。 Lockit被毒死以应用最先进的技术，下一个 科学合作伙伴关系与AMP Aim Cores提供的生成分析，以询问组织和生物学 信息人群中的流体。尽管专注于肾脏和皮肤，但我们的同类群包括所有SLE 表现形式，提供敏捷性，以解决其他器官作为AMP AIM演变。 Lockit承诺和谐 并优化数据管道的所有方面，从收集到分析，解释和传播。