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.

随着在生物学、遗传学和环境调节方面发现系统性红斑狼疮的步伐加快， 而翻译应用的效率就显得更加重要。现在出现了前所未有的 有机会利用技术进步来消除和重建巨大的表型和 这种典型的自身免疫性疾病的免疫学异质性。建立在我们的临床基础设施和 为转录和蛋白质组学提供高质量组织、尿液和外周细胞的技术方案 AMP1中的分析，一个由多学科调查人员组成的扩大团队共同组成了狼疮Omics 皮肤肾脏研究小组(Lockit)回应FOA：加速医学合作 自身免疫和免疫介导性疾病(AMP AIM)计划。集体团队讨论使 具有临床需求的最重要的科学机会是专注于肾脏和皮肤，每一个都有自己的 具有挑战性的异质性。了解早期肾脏疾病的分子基础(与 与AMP1中产生的已确诊/复发疾病的数据进行比较)和总体治疗不足 被认为是该领域的高优先目标，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。向其他团队提供纸巾 将是互补的，因为生物学是在不同疾病之间进行比较的。复制AMP1的成功，Lockit将 由AMP1 SLE临床工作组联合主席Jill Buyon、纽约大学医学院和Michelle领导 佩里，约翰·霍普金斯大学。俄亥俄州立大学的肾病学家布拉德·罗文也加入了他们的行列， 宾夕法尼亚大学皮肤科医生维多利亚·沃思，每个人都因翻译对系统性红斑狼疮的贡献而受到认可。 为了完成我们的指令并确保代表不足的少数民族在 患者，包括由艾伯特·爱因斯坦医学院的安娜·布罗德领导的三个高招募AMP1网站； 玛丽亚·达尔埃拉，加州大学旧金山分校；詹妮弗·阿诺利克，罗切斯特大学(联合主席 RA部位的AMP1和PI，增加B细胞的特长)。由凯伦·科斯滕巴德领导的两个新网站，Brigham和 妇女医院和德克萨斯大学西南分校的Ben Chong带来了患者预后和 分别为皮肤性狼疮。所有人都与总计5541人的队列一起协作和发布 患者同意登记，并存档样本，包括98,980份纵向血液衍生品，以及 3311例肾脏和715例皮肤活检。统一锚定发现，如在AMP1中，杰夫·霍金，加州大学 密歇根州将领导一个数字图像库。Lockit准备应用最先进的技术和下一步 与AMP AIM核心建立科学合作伙伴关系提供生成分析，以询问组织和生物 来自信息量大的人群的体液。虽然侧重于肾脏和皮肤，但我们的队列包括所有SLE 随着AMP AIM的发展，提供了灵活地处理其他器官的能力。洛基特承诺协调 并优化数据管道的所有方面，从收集到分析、解释和传播。