Sjögren’s Team for Accelerating Medicines Partnership (STAMP)

Sjögren 加速药品合作团队 (STAMP)

• 批准号: 10586053
• 负责人: ALAN N BAER
• 金额: $ 160万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586053
• 关键词: Acceleration; Address; Adopted; Advisory Committees; Affect; American; Arthralgia; Atlases; Autoantibodies; Autoimmune; Autoimmune Diseases; Autoimmunity; Award; Biological; Biological Markers; Calibration; California; Cells; Classification; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Research Protocols; Clinical Trials; Clinical assessments; Collaborations; DNA Methylation; Data; Derivation procedure; Diagnosis; Disease; Early Diagnosis; Enrollment; Epidemiology; European; Exocrine Glands; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Fatigue; Foundations; Functional disorder; Funding; Future; Genetic; Genetic Heterogeneity; Genetic Predisposition to Disease; Genomics; Goals; Heterogeneity; Immune; Individual; Inflammation; International; Lacrimal gland structure; Lymphocytic Infiltrate; Lymphoma; Mediating; Medical Research; Medicine; Molecular; Molecular Analysis; Molecular Biology; Morbidity - disease rate; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; National Institute of Dental and Craniofacial Research; Natural History; Nature; New York; Nuclear; Oklahoma; Oral; Participant; Pathogenesis; Pathway interactions; Patient Care; Patient Recruitments; Patients; Phase; Phenotype; Positioning Attribute; Prevalence; Protocols documentation; Quality of life; Recording of previous events; Research; Research Personnel; Research Priority; Resources; Rheumatism; Rheumatoid Arthritis; Rheumatology; Risk; Salivary Gland Tissue; Salivary Glands; Sampling; San Francisco; Scientist; Site; Sjogren' s Syndrome; Standardization; Syndrome; System; Systems Biology; Technology; Therapeutic; Tissues; Translating; Universities; Validation; Work; cell type; cohort; college; deep sequencing; design; effective therapy; eye dryness; follow-up; genetic association; genetic variant; genome wide association study; genome-wide; high risk; improved; multidisciplinary; pre-clinical; reconstruction; recruit; response; risk variant; scale up; single cell mRNA sequencing; symptom management; systemic autoimmune disease; therapeutic target; transcriptome sequencing; transcriptomics; whole genome

ABSTRACT Sjögren’s Disease (SjD, formerly known as Sjögren’s syndrome) is a common systemic autoimmune rheumatic disorder second only to rheumatoid arthritis in prevalence. It primarily affects salivary and lacrimal glands through lymphocytic infiltration and autoantibody-mediated inflammation, resulting in significant morbidity. Approximately one third of SjD patients have extraglandular involvement and have a remarkably elevated risk for lymphoma. Unfortunately, limited progress has been made in addressing the many unmet needs in SjD. Confirmatory diagnosis is multidisciplinary in nature and often results in significant delay. Scant therapeutic options exist outside of symptom management, and results from recent clinical trials have been disappointing. Thus, a better understanding of the pathogenetic mechanisms of disease is critical, and can be achieved using a de- and re-construction approach. Central to this goal, is the need for deeply characterized patients with SjD. The multidisciplinary Sjögren’s Team for Accelerating Medicines Partnership (STAMP) is ideally poised to assemble this resource. The team’s expertise includes autoimmunity-focused molecular biology, genetic, and epidemiologic/clinical research, and a remarkable track-record in establishing large cohorts of participants with stored biospecimens and exquisitely detailed phenotypic characterization. In addition to recruiting new participants, the existing cohorts will provide the unique opportunity to perform 10 to 15-year follow-up of previously evaluated SjD participants. Our proposed Disease Team (DT) is strategically positioned to apply cutting-edge technologies to interrogate the tissue and systems biology of SjD to identify therapeutic pathways and targets, with the following aims: 1) Planning Phase: Develop a 5-year scientific research agenda and SOPs for phenotyping SjD patients in collaboration with other AMP DTs and Technology and Analytics Cores (TACs). Design standardized protocols to recruit, enroll, collect biospecimens and perform deep phenotyping of observational cohorts of SjD and controls. Identify research priorities for SjD to better understand the molecular and phenotypic heterogeneity and natural history at both tissue and cell levels; 2) Pilot Phase: Calibrate clinical assessments and sample procurement across recruitment sites and evaluate SOPs. We will work closely with other DTs and TACs to a) finalize SOPs and implement them at all sites; b) leverage our multidisciplinary expertise to initiate the deconstruction-reconstruction of SjD via preliminary analyses of molecular and clinical data; 3) Scale up Phase: Increase participant recruitment and work with TAC to molecularly deconstruct and reconstruct SjD. Standardized protocols implemented across sites will enable STAMP to interrogate the tissue and systems biology of SjD using deep sequencing and other cutting-edge technologies, to better understand 1) the pathogenesis of SjD and identify therapeutic targets, and new biomarkers; and 2) disease mechanisms inherent to progression of SjD from non-SjD to SjD, and from “early SjD” to “advanced SjD”.

抽象的 干燥病（SjD，以前称为干燥综合征）是一种常见的全身性自身免疫性疾病 风湿性疾病的患病率仅次于类风湿性关节炎。主要影响唾液腺和泪腺 腺体通过淋巴细胞浸润和自身抗体介导的炎症，导致显着 发病率。大约三分之一的 SjD 患者有腺外受累，并且有显着的 患淋巴瘤的风险增加。不幸的是，在解决许多未满足的问题方面取得的进展有限 SjD 的需求。确认诊断本质上是多学科的，通常会导致严重延误。很少 症状管理之外还存在治疗选择，最近的临床试验结果已被证实 令人失望。因此，更好地了解疾病的发病机制至关重要，并且可以 可以通过解构和重构的方法来实现。这一目标的核心是需要深入 SjD 患者的特征。多学科 Sjögren 加速药品合作团队 (STAMP) 非常适合收集此资源。该团队的专业知识包括专注于自身免疫 分子生物学、遗传学和流行病学/临床研究，以及在建立 大量参与者拥有储存的生物样本和极其详细的表型特征。 除了招募新参与者之外，现有的团队还将提供独特的机会来表现 对先前评估的 SjD 参与者进行 10 至 15 年的随访。我们提议的疾病小组 (DT) 是 战略定位为应用尖端技术来询问组织和系统 SjD 的生物学，以确定治疗途径和目标，目标如下： 1) 规划阶段： 合作制定 SjD 患者表型分型的 5 年科学研究议程和 SOP 与其他 AMP DT 以及技术和分析核心 (TAC) 一起使用。设计标准化协议 招募、登记、收集生物样本并对 SjD 和 SjD 的观察队列进行深度表型分析 控制。确定 SjD 的研究重点，以更好地了解分子和表型异质性 组织和细胞水平的自然史； 2) 试点阶段：校准临床评估和 对各个招聘网站的采购进行抽样并评估 SOP。我们将与其他 DT 密切合作 和 TAC a) 最终确定 SOP 并在所有地点实施； b) 利用我们的多学科专业知识 通过分子和临床数据的初步分析，启动 SjD 的解构重建； 3） 扩大阶段：增加参与者招募并与 TAC 合作进行分子解构和 重建 SjD。跨站点实施的标准化协议将使 STAMP 能够询问 SjD的组织和系统生物学利用深度测序和其他尖端技术，更好地 了解 1) SjD 的发病机制并确定治疗靶点和新的生物标志物； 2) 疾病 SjD 从非 SjD 到 SjD、从“早期 SjD”到“高级 SjD”发展的固有机制。