University of Chicago Autoimmunity Center of Excellence

芝加哥大学自身免疫卓越中心

• 批准号: 8477111
• 负责人: Marcus Ramsay Clark
• 金额: $ 60.44万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-10 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8477111
• 关键词: Autoimmune Diseases; Autoimmune Process; Autoimmunity; Basic Science; Biological Markers; Biological Response Modifier Therapy; Biological Sciences; Categories; Cell Separation; Cells; Chicago; Clinical; Clinical Sciences; Clinical Trials; Committee Members; Communities; Complement; Conduct Clinical Trials; Core Facility; Coupled; Development; Discipline; Disease; Ensure; Evolution; Faculty; Failure; Family; Fostering; Gastroenterology; Goals; Heterogeneity; Human; Immune response; Immune system; Immunoglobulins; Immunology; Individual; Inflammatory Bowel Diseases; Interdisciplinary Study; Investigation; Laboratories; Lead; Light-Chain Immunoglobulins; Lymphocyte; Lymphocyte Subset; Medical center; Mentorship; Mission; Modeling; Multiple Sclerosis; Myasthenia Gravis; Nephrology; Neurology; Participant; Pathogenesis; Patients; Peer Review; Phase; Population; Procedures; Process; Research; Research Institute; Research Personnel; Resources; Rheumatology; Scientist; Self Tolerance; Societies; Structure; System; Systemic Lupus Erythematosus; Therapeutic; Therapeutic Clinical Trial; Therapeutic Studies; Translational Research; Universities; adaptive immunity; career; experience; human disease; innovation; insight; lectures; meetings; multidisciplinary; new technology; novel; novel strategies; novel therapeutics; programs; therapeutic target; tool

DESCRIPTION (provided by applicant): Patients with autoimmune diseases are categorized by clinical manifestations and simple laboratory values. However recent mechanistic investigations, and experience with directed biological therapies, have demonstrated that these autoimmune disease categories are very heterogeneous. Despite this apparent heterogeneity most, if not all, autoimmune diseases share a common theme. They arise from failures in self tolerance. Therefore, we propose to establish the University of Chicago Autoimmunity Center of Excellence (UCACE) with the purpose of studying and manipulating lymphocyte tolerance in patients with diverse autoimmune diseases including systemic lupus erythematosus (SLE), myasthenia gravis (MG) and inflammatory bowel disease (IBD). Central to this effort will be the establishment of a core facility, the Autoimmune Lymphocyte Repertoire Core (ALRC) that will enable investigators from multiple disciplines to assess the evolution of humoral autoimmunity in rare human lymphocyte subpopulations. The singular research focus of the UCACE will be complemented by an innovative clinical trials program, and administrative structure, that will facilitate mechanistic studies in patients receiving novel lymphocyte-directed therapies. Understanding how lymphocyte tolerance is breached in different autoimmune diseases will reveal commonalities and differences that will enable the development of new biomarkers and novel therapeutics. RELEVANCE: Autoimmunity is manifest in a myriad of diseases that preferentially afflict younger patients who are often pursing careers and raising families. The total burden of autoimmune diseases on society is substantial. The focus of the current application is the pathogenesis of human autoimmunity. It is anticipated that these studies will contribute to the development of new therapies to treat those afflicted with autoimmune diseases. Clinical Component: Clinical Component of University of Chicago Autoimmunity Center of Excellence (Hanauer, S) CLINICAL COMPONENT DESCRIPTION (Provided by applicant): The University of Chicago clinical, translational and basic science programs form an interactive network of research and clinical resources focused on understanding and treating human disease. Integration of clinical and basic science missions is ensured by a common administrative structure in which both the University of Chicago Medical Center and Biological Sciences Division (BSD) are under a single Dean/CEO Office that oversees and defines the priorities of both enterprises. Integration is then reinforced by a system of common core facilities, multidisciplinary research institutes, centers and programs and, ultimately, by faculty who broadly collaborate in both the research and clinical activities of the University. The University of Chicago Autoimmunity Center of Excellence proposes to establish a Clinical Trials Program (UCACE-CTP) that will capitalize on this established clinical-academic structure to create and conduct clinical trials in autoimmunity that are tightly coupled to mechanistic studies. Successful models for accomplishment of this aim are already well established within the participating clinical sections and departments of the UCACE. Therefore, the primary goal of the UCACE-CTP will be to standardize procedures for clinical trials management across clinical center participants and to provide a common platform integrating efforts within the UCACE and ACE networks. Finally, the UCACE-CTP will develop a system of mentorship and peer review that will encourage clinical and translational investigators to develop novel therapeutic and mechanistic studies on patients with autoimmune disease. RELEVANCE: The purpose of the University of Chicago Autoimmunity Center of Excellence (UCACE) Clinical Trials Program is to promote clinical trials in autoimmunity that are tightly coupled to insightful mechanistic studies. This goal is highly relevant to developing new therapies for patients with autoimmunity.

描述（由申请人提供）：自身免疫性疾病患者根据临床表现和简单的实验室检查值进行分类。然而，最近的机制研究和定向生物治疗的经验表明，这些自身免疫性疾病的类别是非常异质性的。尽管这种明显的异质性，大多数，如果不是全部，自身免疫性疾病有一个共同的主题。它们源于自我宽容的失败。因此，我们建议建立芝加哥大学自身免疫卓越中心（UCACE），目的是研究和操纵各种自身免疫性疾病患者的淋巴细胞耐受性，包括系统性红斑狼疮（SLE）、重症肌无力（MG）和炎症性肠病（IBD）。这项工作的核心将是建立一个核心设施，即自身免疫淋巴细胞库核心（ALRC），使来自多个学科的研究人员能够评估罕见人类淋巴细胞亚群中体液自身免疫的演变。UCACE的单一研究重点将得到创新的临床试验计划和管理结构的补充，这将促进接受新型淋巴细胞导向疗法的患者的机制研究。了解淋巴细胞耐受性如何在不同的自身免疫性疾病中被破坏将揭示共性和差异，这将使新的生物标志物和新的治疗方法的开发成为可能。相关性：自身免疫性表现在无数的疾病中，这些疾病优先折磨那些经常追求事业和养家糊口的年轻患者。自身免疫性疾病对社会的总负担是巨大的。当前应用的焦点是人类自身免疫的发病机制。预计这些研究将有助于开发新的疗法来治疗那些患有自身免疫性疾病的人。 临床部分：芝加哥大学自身免疫卓越中心（Hanauer，S）的临床部分 临床组件描述（由申请人提供）：芝加哥大学的临床、转化和基础科学项目形成了一个研究和临床资源的互动网络，专注于了解和治疗人类疾病。临床和基础科学任务的整合由一个共同的行政结构确保，其中芝加哥医学中心和生物科学部（BSD）的大学都在一个单一的院长/首席执行官办公室，监督和定义两个企业的优先事项。然后，通过共同的核心设施，多学科研究机构，中心和项目的系统，并最终通过在大学的研究和临床活动中广泛合作的教师来加强整合。芝加哥大学自身免疫卓越中心建议建立一个临床试验计划（UCACE-CTP），该计划将利用这一既定的临床学术结构，创建和开展与机制研究紧密结合的自身免疫临床试验。实现这一目标的成功模式已经在UCACE的参与临床部门和部门中建立起来。因此，UCACE-CTP的主要目标是标准化临床试验参与者的临床试验管理程序，并提供一个统一的平台，整合UCACE和ACE网络内的工作。最后，UCACE-CTP将开发一个指导和同行评议系统，鼓励临床和翻译研究人员开发针对自身免疫性疾病患者的新型治疗和机制研究。相关性：芝加哥大学自身免疫卓越中心（UCACE）临床试验计划的目的是促进与有见地的机制研究紧密结合的自身免疫临床试验。这一目标与开发针对自身免疫患者的新疗法高度相关。