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 Sjögren病（SJD，以前称为Sjögren'sSyndrome）是一种常见的全身自身免疫性 风湿病仅次于类风湿关节炎。它主要影响唾液和泪 通过淋巴细胞浸润和自身抗体介导的炎症的腺体，导致显着 发病率。大约三分之一的SJD患者患有外部受累，并且具有明显的 淋巴瘤风险升高。不幸的是，解决了许多未满足的事情，取得了有限的进展 SJD的需求。确认性诊断本质上是多学科的，通常会导致明显的延迟。很少 症状管理以外的治疗选择存在，最近的临床试验的结果是 令人失望。这是对疾病的致病机制的更好理解至关重要，并且可以 可以使用DE-和重建方法来实现。这个目标的核心是需要深入 SJD患者的特征。多学科Sjögren的团队，用于加速药品合作伙伴关系 （邮票）是理想的中毒来组装此资源。该团队的专业知识包括以自身免疫性为中心 分子生物学，遗传学和流行病学/临床研究，以及建立的显着轨道记录 大量具有存储生物测量的参与者和精确的表型表征。 除了招募新参与者之外，现有同伙还将提供独特的机会来表演 先前评估的SJD参与者的10至15年随访。我们提出的疾病小组（DT）是 在战略上定位以应用尖端技术来询问组织和系统 SJD的生物学以识别治疗途径和靶标，其目的：1）计划阶段： 为合作的SJD患者制定5年的科学研究议程和SOP 与其他AMP DTS以及技术与分析核心（TACS）。设计标准化协议 招募，注册，收集生物测量并对SJD的观察队列进行深层表型 控件。确定SJD的研究优先级，以更好地了解分子和表型异质性 组织和细胞水平的自然历史； 2）试点阶段：校准临床评估和 跨招聘地点采购采购并评估SOP。我们将与其他DT紧密合作 和TACs a）最终确定SOP并在所有站点上实施； b）利用我们的多学科专业知识 通过对分子和临床数据的初步分析来启动SJD的解构重建； 3） 扩展阶段：增加参与者的招聘并与TAC一起工作以分子解构和 重建SJD。跨站点实施的标准化协议将使邮票审问 SJD的组织和系统生物学使用深层测序和其他尖端技术，以更好地 了解1）SJD的发病机理并鉴定治疗靶标和新的生物标志物； 2）疾病 SJD从非SJD到SJD的进展固有的机制，从“早期SJD”到“高级SJD”。