实验室实体依托北京大学第三医院和北京大学医学部而建立，由实验室科学家和临床医生科学家团队合作研究开发基于中枢和外周体液的神经退行性疾病生物标志物，用以疾病的早期预警诊断、临床干预效果评估、和疾病病程分类等，建立一套适合符合中国人发病及临床特点的神经退行性疾病早期诊断和预警的综合诊断指标体系。

　　研究内容主要涵盖三个方面：1】利用组学和各种细胞分子生物学方法发现体液尤其是外周体液来源的具有诊断，预后、临床干预疗效评和疾病分类价值的核酸，蛋白或脂类标志物，拓展神经退行性疾病早期诊断标志物发现的新领域；2】联合北京地区和国内其他临床医院建立神经退行性疾病临床大型队列，完善脑脊液与外周体液样本库、影像学数据库、分子生物标志物数据库。3】疾病相关重要蛋白如α核突触蛋白，Tau，Aβ等在帕金森疾病，阿尔茨海默疾病，运动神经元疾病等疾病分子生物机制研究。

　　实验室主任是章京教授、神经病理学博士，主要学术带头人樊东升教授和肖卫忠教授是北医三院的神经病治疗领域的知名医生科学家。所有23名参与重点室研究任务的人员中70%具有神经生物和病理专业的中高级职称，横跨基础研究、临床医疗和病理诊断领域的团队合作是该重点实验室完成研究目标的优势和基础。目前实验室空间面积超过2.5千平米，配备完整的细胞和分子生物学研究基本仪器设备，也购置了先进的各种分析仪器，如Nanostring外泌体分析仪, MSD 电化学免疫荧光测定仪、3500系列基因分析仪，数字PCR仪等，满足高通量超灵敏筛选潜在蛋白/核酸生物标志物的研究需求。

　　研究团队多年从事脑脊液、血液和唾液中生物标记物的研究，特别是用于帕金森和阿尔茨海默病等早期诊断及追踪。建立了Luminex、MesoScale和Singulex等高通量、高灵敏度与准确度蛋白免疫标准化测试平台，关于外周体液来源的生物标志物发现、验证、机理研究与大样本的测试及临床应用方面处于国际前沿，参与了国际上关于AD脑脊液中生物标记物测定的多中心、标准化研究；章京教授实验室首次发现，错误折叠的α-突触核蛋白（PD生物标志物之一）可以激活中枢的小胶质细胞引发炎症反应。独立开发了一套利用合并的样本进行质谱分析筛选、然后针对筛选出的候选蛋白或肽在独立、单独样本中进行验证的流程。

 

　　机构负责人：樊东升

　　联系人：贾熙华

　　邮箱：jiaxihua_glia@163.com

　　电话：82802614

　　地址：北京市海淀区学院路38号

　　

　　Beijing Key Laboratory of Research and Translation of Neurodegenerative Disease Biomarkers

 

　　The establishment of Beijing Key Laboratory for Research and Translation of Neurodegenerative Disease Biomarkers was approved by Beijing Municipal Science &Technology Commissionin December of 2016. It is located in the Department of Pathologybuilding of Peking University Third hospital, along with several spaces affiliated with the Department of Pathology of Health Science Center of Peking University. The key laboratory brings together scientists and clinicians to collaborate on the studies of neurodegenerative diseases, such as Alzheimer’s disease(AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), etc , with emphasis on discovering biomarkersfor early diagnosis of neurodegenerative disorders. With a fast expanding aging population in China, there is an urgent need for the development of sensitive and specific biomarkers for detection and diagnosis  at an early stage, when curative interventions are still possible. Furthermore，part of our ongoing efforts is to carry out large scale cohort studies of Chinese patients,so biomarkers found would be tailored to the need of Chinese patients. Translating our pioneering bench/bed-side work to the novel applications for AD or PD patients is the fundamental vision behind the establishment of Beijing Key Laboratory of Research and Translation of Neurodegenerative Disease Biomarkers.

 

　　Age related neurological diseases are becoming a major social and economic problem worldwide, China is no exception. There is growing requirement to use biomarkers in clinical development programs for diseases like AD, PD and related disorders, as it is well known that biomarkers could precisely classify a disease and guild therapeutic interventions. The research work of the lab will therefore center on three topics. First, biomarkers for early detection, predicting prognosis, monitoring the effects of clinical intervention and assessing the treatment strategies that are most likely to be efficacious. By harnessing the power of our cutting edge approaches and instruments, we will explore masses of omics datasets and identify novel biomarker candidates from body fluids including blood, urine, saliva, CSF, etc. One of the major areas of focus in this lab is exosomes, which are emerging as a novel form of cell-cell communication.Our laboratory currently ramps up a comprehensive suite of genomic, molecular and protein-based platforms for assays of neural cell derived exosomes to develop new biomarkers. Second, qualification, validation and testing of peripheral fluid derived biomarkers on the cohort studies. It is critical to assess the reliability of particular molecule candidate, whether it is exosome based or not, for diagnostic or predictive signatures of diseases. Finally, we will further our studies by trying to elucidate the mechanism underlying the biomarkers found, with focus on their biological function under physiological and pathological conditions. This process will help scientists and clinicians to better appreciate the mode of action of a particular biomarker that plays at cellular and molecular level, ultimately optimizing their clinical application and successfully transforming into reliable and accurate diagnosis tools.

　　In a nut shell, the key laboratory’ s research portfolio spans from biomarker development, study of molecular and cellular mechanisms of neurodegeneration, and all the way to clinical trials, with the hope to transform our science from bench to bedside that directly benefit patients with neurodegenerative disorders.

 

　　Prof. Zhang Jing is the Director of Beijing Key Laboratory of Research and Translation of Neurodegenerative Disease Biomarkers. As an internationally renowned scientist in the field of neuropathology and biomarkers investigation, for over 20 years ,Prof. Zhang and his team have built up extensive track record including a broad range of biomarker study related publications in neurodegenerative diseases, especially PD and AD. He also has hands-on experience in carrying out large scale clinical trials.

　　Dr. Fang Dongsen, a principle investigator of the key lab, is a well-known clinician with more than 20 years of clinical experience, especially (ALS). Dr. Fang focuses on understanding the pathological mechanism of ALS and developing new therapies for people suffering from ALS, as well as identifying biomarkers of ALS.

　　Dr. Xiao Weizhong, alsoa principle investigator of the lab, is a trained neurologist for neurodegenerative diseases. Dr. Xiao’s team is responsible for the buildup of a sample library of clinical body fluids, including blood, urine, salvia and cerebral spinal fluid (CSF), collected from patients with AD, PD or other related neurodegenerative diseases. 

　　The scientific staff of the key laboratory consists of 23 well educated members, over 70% with PhD degree in biology/neurology discipline. The others are well trained technicians with advanced expertise. Our clinicians, physician-scientists and basic science researchers will team up to share their expertise, brainstorm, and collaborate in all research projects. The Third hospital and Health science center generously support our laboratory by offering approximately 2,500 square meters of laboratory space equipped with multiple basic biological lab instruments and state-of-the-art platforms. For example, the lab currently has Nanostring, MSD Electrochemiluminescent platform, Applied Biosystems 3500 Series Genetic Analyzer, SMC？ Single Molecule Counting (SMC？) system, and other high-through put screen and detecting platform to search for multiple biomolecules in parallel at ultra low levels, with improved sensitivity. The key laboratory is poised to make significant strides in the development of reliable biomarkers for early stage diagnosis of neurodegenerative disease.

　　Over the last 10 years, Zhang lab has contributed substantially to the understanding of the physiology and pathology of α-synuclein (α-Syn) in PD, AD and related disorders. Indeed, his lab is the first to report that α-Syn aggregates trigger inflammatory reaction in microglia via a dysregulated process of phagocytosis and NADPH oxidase activity. Another major area of Dr. Zhang’s team is proteomics-based discovery work, as well as targeted validation of candidate proteins related to neurodegenerative disorders including AD and PD. As one of the leaders in the AD and PD biomarker field, Dr. Zhang has used both mass spectrometry (MS) and immunoassay techniques on numerous platforms (xMAP Luminex, MSD and ELISA) to discover and then develop assays (SRM, immunoassays, including de novo ones) for protein/peptide biomarkers in several different biospecimens (brain tissue, CSF, blood plasma and saliva). Most of these studies have been conducted in collaboration with multiple medical centers located domestically and internationally, with many papers published. Finally, immunoaffinity-based isolation neuron derived exosomes from peripheral body fluids is originally developed in Zhang laboratory with adaptation by many other labs.  

　　

　　Director: Fan Dongsheng

　　Contact Person: Jia Xihua

　　Email: jiaxihua_glia@163.com

　　TEL:82802614

　　Address: No. 38 Xueyuan Road, Haidian District, Beijing, China