Cornell ME/CFS Collaborative Research Center

总体项目摘要-康奈尔大学/CFS合作研究中心 尽管在美国估计有100万或更多的人患有Myalgic 脑脊髓炎/慢性疲劳综合征(ME/CFS)，对其病因知之甚少 疾病和有效的治疗方法都是缺乏的。ME/CFS的特点是虚弱的疲劳，而不是 通过休息或由于任何其他健康状况而改善，以及无数的症状，包括 肌肉骨骼疼痛、头痛、认知困难、立位不耐受和睡眠障碍。那里 没有对这种疾病进行简单的科学验证的测试，这导致了临床医生的极大不确定性 在评估报告长期和不明原因的疲劳的患者时。疲劳和其他症状是 在超过患者的特定阈值后加重，已知的ME/CFS的特征症状 作为运动后不适(PEM)。缺乏这种疾病的生物标志物和缺乏可用的 ME/CFS的研究模型放大了迄今为止在该领域产生的研究数据的不足。近期 研究表明ME/CFS存在免疫调节失调和神经炎症。通过利用这一经验， 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的背景 医学院、伊萨卡学院和博伊斯·汤普森研究所)，以及来自许多其他机构的关键人员 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、代谢组学以及单细胞RNA和微RNA测序方法 通过彻底检查来自以下来源的生物标记物，揭示导致ME/CFS的潜在生物医学机制 通过运动刺激症状前后的患者和对照组。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 细胞外小泡的分子、新陈代谢和运输(项目2)和(3)决定基因水平 整个免疫系统的失调(项目3)。这三个研究项目得到了两个 核心；一个临床核心(核心1：康奈尔结直肠癌临床核心)，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)，它将支持儿童权利委员会成员进行数据管理和生物信息学分析，而 跨项目组件吸收数据，以提供所分析特征的综合视图 关于该中心研究的ME/CFS课题。中心的所有活动将通过 行政核心，它将促进中心内部的协同和整合，同时也是平台 用于与其他协作研究中心和数据管理协调中心协作。 行政核心还将负责外联活动，旨在提高认识和 在研究界、卫生专业人员和普通公众中了解ME/CFS。

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.