Cornell ME/CFS Collaborative Research Center

总体项目摘要-康奈尔ME/CFS合作研究中心 尽管美国估计有100万或更多的人患有肌痛症， 脑脊髓炎/慢性疲劳综合征（ME/CFS），关于其病因学知之甚少。 缺乏有效的治疗方法。ME/CFS的特征是使人虚弱的疲劳， 通过休息或由于任何其他医疗条件而改善，以及无数的症状，包括 肌肉骨骼疼痛、头痛、认知困难、直立不耐受和睡眠障碍。那里 没有简单的科学验证的疾病测试，导致临床医生之间存在很大的不确定性 当评估报告长时间和原因不明的疲劳的患者时。疲劳和其他症状 在超过患者特定阈值的运动后加重，这是ME/CFS的标志性症状， 运动后不适（PEM）。缺乏疾病的生物标志物和缺乏可用的 ME/CFS的研究模型扩大了迄今为止在该领域产生的研究数据的不足。最近 研究表明ME/CFS中存在免疫失调和神经炎症。通过利用经验， 来自四个不同机构（康奈尔伊萨卡，威尔康奈尔）的研究人员的能力和不同背景 医学，伊萨卡学院和博伊斯汤普森研究所），以及来自许多其他 组织，拟议的康奈尔ME/CFS合作研究中心将应用神经成像， 蛋白质组学，代谢组学，单细胞RNA和microRNA测序方法来询问 潜在的生物医学机制，有助于ME/CFS，通过彻底检查生物标志物， 患者和对照组之前和之后的症状激发通过运动。三个研究项目将 寻求（1）检查大脑中的氧化应激和神经炎症（项目1），（2）检查炎症 细胞外囊泡的分子、代谢和货物（项目2）和（3）决定基因水平 免疫系统的失调（项目3）。这三个研究项目由两个 核心;一个临床核心（核心1：Cornell CRC临床核心），将招募和筛选患者/对照 并监督心肺运动测试和研究核心（核心2：综合数据分析 核心），将支持CRC成员进行数据管理和生物信息学分析， 吸收项目各组成部分的数据，以提供分析特性的综合视图 关于中心研究的ME/CFS主题。中心的所有活动将通过一个 行政核心，这将促进中心内的协同作用和整合，同时也是一个平台， 与其他合作研究中心和数据管理协调中心合作。 行政核心还将负责外联活动，旨在提高认识， 了解ME/CFS在研究界，卫生专业人员和公众。

OVERALL PROJECT SUMMARY – CORNELL ME/CFS COLLABORATIVE RESEARCH CENTER Despite the fact that an estimated 1 million people or more in the U.S. suffer from Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), remarkably little is known about the etiology of the disease and effective therapies are lacking. ME/CFS is characterized by debilitating fatigue that is not ameliorated by rest or due to any other medical condition, and a myriad of symptoms, including musculoskeletal pain, headaches, cognitive difficulties orthostatic intolerance, and sleep disturbances. There are no simple scientifically validated tests for the illness, leading to a great deal of uncertainty among clinicians when evaluating patients who report prolonged and unexplained fatigue. Fatigue and other symptoms are exacerbated following exertion beyond a patient's particular threshold, a hallmark symptom of ME/CFS known as post-exertional malaise (PEM). The absence of biomarkers for the disease and the lack of available research models for ME/CFS amplify the deficiency of research data produced in the field to date. Recent studies implicate immune dysregulation and neuroinflammation in ME/CFS. By leveraging the experience, capabilities and varied backgrounds of researchers from four different institutions (Cornell Ithaca, Weill Cornell Medicine, Ithaca College, and Boyce Thompson Institute), as well as key personnel from many other organizations, the proposed Cornell ME/CFS Collaborative Research Center will apply neuroimaging, proteomics, metabolomics, and single cell RNA and microRNA sequencing approaches to interrogate the underlying biomedical mechanisms that contribute ME/CFS, by thorough examination of biomarkers from patients and controls both before and after symptom provocation through exercise. Three research projects will seek to (1) examine oxidative stress in the brain and neuroinflammation (Project 1), (2) examine inflammatory molecules, metabolism, and cargo of extracellular vesicle (Project 2) and (3) determine levels of gene dysregulation across the immune system (Project 3). These three research projects are supported by two cores; one Clinical Core (Core 1: Cornell CRC Clinical Core), which will recruit and screen patients/controls and oversee cardiopulmonary exercise testing and a Research Core (Core 2: Integrative Data Analysis Core), which will support CRC members with data management and bioinformatics analyses, while assimilating data across the project components to provide an integrated view of the assayed characteristics about ME/CFS subjects studied by the Center. All Center activities will be coordinated through an Administrative Core, which will foster synergy and integration within the Center, while also being the platform for collaboration with other Collaborative Research Centers and the Data Management Coordinating Center. The Administrative Core will also be responsible for outreach activities, designed to increase awareness and understanding of ME/CFS within the research community, health professionals, and the general public.