Center for Mucosal Immunobiology and Rheumatic Disease Pathogenesis

粘膜免疫生物学和风湿病发病机制中心

• 批准号: 10700077
• 负责人: Vernon Michael Holers
• 金额: $ 75.06万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700077
• 关键词: Attention; Autoantigens; Autoimmune Diseases; Autoimmunity; Biological Markers; Blood specimen; CLIA certified; Cell Communication; Cells; Chronic; Clinical; Collaborations; Colorado; Communication; Computer Analysis; Consultations; Data; Data Analyses; Data Science; Data Science Core; Data Set; Development; Diagnostic; Direct Costs; Disease; Education; Environment; Epidemiology; Epithelium; Evolution; Funding; Future; Goals; Grant; Grant Review; Healthcare Systems; Human; Immunobiology; Immunologic Markers; Immunologic Techniques; Immunology; Individual; Inflammation; Inflammatory; Infrastructure; Institution; Investments; Letters; Medicine; Mesenchymal; Methodology; Methods; Mission; Molecular; Mucosal Immune Responses; Mucosal Immune System; Mucous Membrane; Newsletter; Online Systems; Outcome; Participant; Pathogenesis; Pathway interactions; Patient Care; Patients; Peripheral; Phase; Phenotype; Play; Population; Population Sciences; Population Study; Populations at Risk; Process; Program Development; Research; Research Personnel; Resources; Rheumatism; Rheumatoid Arthritis; Role; Sampling; Sampling Studies; Scholars Program; Science; Series; Services; Source; Spondylarthropathies; Study Subject; Systemic Lupus Erythematosus; Technology; Technology Assessment; Testing; Therapeutic; Tissue Sample; Tissues; Training; Translating; Translations; Universities; biobank; biomarker development; biomarker identification; career; clinical care; cohort; commercialization; complex data; data management; design; direct patient care; discount; disease classification; dysbiosis; early detection biomarkers; human disease; improved; improved outcome; innovation; insight; interest; member; metabolome; metabolomics; microbial; microbiome; microbiome analysis; mid-career faculty; mucosal site; novel; novel marker; novel strategies; novel therapeutics; outreach; peripheral blood; personalized medicine; pre-clinical; prevent; professor; programs; recruit; research and development; single cell technology; skills; social media; symposium; systemic autoimmunity; systemic inflammatory response; therapy development

A substantial cadre of investigators at the University of Colorado are focused on characterizing the molecular origins and causal mechanisms that drive the initiation and preclinical phases of rheumatic and autoimmune diseases. One of the most important outcomes of those efforts has been the demonstration in populations at- risk for future disease that dysbiosis and chronic inflammation at mucosal sites can promote the initial local development of disease-specific loss of tolerance to autoantigens. Ultimately, this process leads to systemic autoimmunity and the development of diseases including rheumatoid arthritis (RA) and spondyloarthroarthritis (SpA). Building on that concept with unique at-risk populations and an extensive programmatic infrastructure, a P30 Rheumatic Disease Research Resource Center (RDRRC) entitled “Center for Mucosal Immunobiology and Rheumatic Disease Pathogenesis” is proposed. Included in the Center are an Administrative Core, a Population and Data Sciences Core, and a Mucosal Immunobiology Core. This Center is specifically designed to facilitate studies of human disease pathogenesis that incorporate the broad range of mucosal and systemic immunologic techniques, as well as develop new approaches, to study these integrated mechanisms in already recruited cohorts of individuals throughout the preclinical and then clinically active phases of disease. The Center includes 43 internal and external members who have in aggregate $77M in related annual direct cost grant funding. In addition to providing access to stored biospecimens and data from ongoing population studies, the Center will provide consultative and member discount mechanisms for all of the critical aspects of cohort development, epidemiologic assessment, data management and data analyses. In addition, the Center will provide members access to technologies that focus on analyses of the microbiome and microbial:cell interactions, as well as informative mucosal and peripheral immune biomarkers. The Center will build on a recent $80M investment from the Dean to fund four other relevant programs with which this Center will interact. Dr. Michael Holers, Professor of Medicine and Immunology, will serve as the Center Director, and Dr. Kristi Kuhn, Associate Professor of Medicine, will serve as the Associate Director. Both will interact with Advisory and Executive Committees, and in the latter will be joined by Core Directors and Co-Directors with domain expertise. As a key component of the mission of the Center, a Pilot & Feasibility Grants Program will be developed with substantial institutional support. Additional Enrichment Program activities will include a seminar series, technology assessment series, and an annual symposium. A major focus will be on early career investigator development through enhanced Core access as well as Grants Review and a Scholars Programs. Social media, web-based outreach and newsletters will provide comprehensive communication. Finally, a Patient Impact Program will be utilized for the assessment and enhanced translation of novel biomarkers and therapeutically relevant RDRRC discoveries into direct patient care with the goal to improve outcomes.

科罗拉多大学的大量研究人员致力于表征分子 驱动风湿病和自身免疫性疾病起始和临床前阶段的起源和因果机制 疾病。这些努力最重要的成果之一是在人群中进行了展示—— 未来疾病的风险是粘膜部位的生态失调和慢性炎症可以促进最初的局部 疾病特异性的自身抗原耐受性丧失。最终，这个过程会导致系统性的 自身免疫和疾病的发展，包括类风湿性关节炎 (RA) 和脊柱关节炎 （温泉）。在此概念的基础上，以独特的高危人群和广泛的规划基础设施为基础， P30 风湿病研究资源中心 (RDRRC)，题为“粘膜免疫生物学中心” 提出了“风湿病发病机制和风湿病发病机制”的建议。该中心包括一个行政核心、一个 人口和数据科学核心，以及粘膜免疫生物学核心。这个中心是专门设计的 促进人类疾病发病机制的研究，其中包括广泛的粘膜和全身疾病 免疫学技术以及开发新方法来研究这些整合机制 招募了整个疾病的临床前阶段和临床活跃阶段的个体队列。这 中心包括 43 名内部和外部成员，相关年度直接成本总计 7700 万美元 拨款。除了提供对存储的生物样本和持续人口数据的访问之外 研究中，中心将为所有关键方面提供咨询和会员折扣机制 队列开发、流行病学评估、数据管理和数据分析。此外，该中心 将为会员提供专注于微生物组和微生物：细胞分析的技术 相互作用，以及信息丰富的粘膜和外周免疫生物标志物。该中心将建立在 最近，院长投资了 8000 万美元，资助该中心将与之互动的其他四个相关项目。 医学和免疫学教授 Michael Holers 博士将担任中心主任，Kristi 博士将担任中心主任 医学副教授库恩将担任副主任。两者都将与咨询互动 和执行委员会，后者将由核心董事和联合董事加入，其领域 专业知识。作为该中心使命的关键组成部分，试点和可行性资助计划将 是在机构的大力支持下发展起来的。其他强化计划活动将包括研讨会 系列、技术评估系列和年度研讨会。主要重点将是早期职业生涯 通过增强核心访问以及资助审查和学者计划来促进研究者发展。 社交媒体、网络推广和时事通讯将提供全面的沟通。最后，一个 患者影响计划将用于评估和增强新型生物标志物的翻译 将与治疗相关的 RDRRC 发现应用于直接患者护理，以改善结果。

项目成果

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

• DOI: 10.3390/cancers15215231
• 发表时间: 2023-10-31
• 期刊: CANCERS
• 影响因子: 5.2
• 作者: Frost, Eleanor;Hofmann, Jonathan N.;Huang, Wen-Yi;Parks, Christine G.;Frazer-Abel, Ashley A.;Deane, Kevin D.;Berndt, Sonja I.
• 通讯作者: Berndt, Sonja I.