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 SLE 生物学、遗传学和环境调控领域发现步伐的加快， 现在，转化应用的效率变得更加重要。 利用技术进步来消除和重建巨大的表型和 这种原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 产生用于转录组和蛋白质组的高质量组织、尿液和外周细胞的技术方案 AMP1 中的分析，这是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 皮肤肾脏调查小组 (LOCKIT) 响应 FOA：加速医学合作 自身免疫和免疫介导的疾病 (AMP AIM) 计划的集体团队讨论一致。 具有临床需求的最重要的科学机会关注肾脏和皮肤，两者都有自己的特点 了解极早期肾脏疾病的分子基础（具有挑战性的异质性）。 与 AMP1 中生成的已确诊/复发疾病的数据进行比较）以及总体治疗不足 被认为是该领域的高度优先目标，以及区分急性和慢性皮肤病和 监测这些皮肤病亚群治疗反应的差异 组织对其他团队的可用性。 当在不同疾病之间进行生物学比较时，LOCKIT 将具有互补性。 由 AMP1 SLE 临床工作组联合主席、纽约大学医学院 Jill Buyon 和 Michelle 领导 约翰·霍普金斯大学的佩特里 (Petri) 和俄亥俄州立大学的肾病学家布拉德·罗文 (Brad Rovin) 也加入了进来。 宾夕法尼亚大学皮肤科医生 Victoria Werth 因对 SLE 的转化贡献而受到认可。 为了完成我们的指令并确保代表性不足的少数群体有足够的代表性 患者，其中包括由阿尔伯特·爱因斯坦医学院的 Anna Broder 领导的三个高招募 AMP1 站点； Maria Dall'Era，加州大学旧金山分校；Jennifer Anolik，罗切斯特大学（联合主席） RA 位点的 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分校的 Ben Chong 带来了患者治疗结果和治疗方面的专业知识 分别与总共 5,541 个队列一起合作并发表。 患者同意登记并存档样本，包括 98,980 份纵向血液衍生物，以及 3,311 个肾脏和 715 个皮肤活检，以统一锚定发现，如 AMP1，Jeff Hodgin，大学。 密歇根州将领导一个数字成像存储库，准备应用最先进的技术和下一步。 与 AMP AIM Cores 的科学合作伙伴提供的生成分析，用于询问组织和生物 虽然我们的研究重点是肾脏和皮肤，但我们的研究对象包括所有系统性红斑狼疮患者。 随着 AMP AIM 的发展，提供解决其他器官问题的灵活性。 优化数据管道的各个方面，从收集到分析、解释和传播。