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吴志英

吴志英,1967年出生,医学博士,浙江大学求是特聘教授,神经内科主任医师,国务院政府特殊津贴专家,国家杰出青年基金获得者。现任浙江大学医学院附属第二医院副院长,中国神经科学学会副理事长,中华医学会神经病学分会神经遗传学组组长,浙江省医学会神经病学分会候任主任委员,浙江省医学神经生物学重点实验室主任。1990年毕业于福建医科大学医学系,1995年福建医科大学神经病学专业硕士毕业,1999年同济医科大学神经病学专业博士毕业。1990-2007年就职于福建医科大学附属第一医院神经内科,历任住院医师、主治医师、副主任医师、主任医师、教授,其中2001-2003年在哥伦比亚大学医学院从事博士后研究工作。2007年9月以复旦大学特聘教授引进到复旦大学附属华山医院,担任神经内科主任医师,复旦大学神经病学研究所所长。2015年8月以浙江大学求是特聘教授引进到浙医二院。获得奖项及荣誉称号包括:省级科技进步奖一等奖1项(第一完成人)及二等奖2项、中国青年科技奖、中国青年女科学家奖、全国优秀科技工作者、国家卫生计生突出贡献中青年专家、首届中国杰出神经内科医师学术成就奖等。

    主要研究方向及内容

    1、神经系统疾病致病基因和风险基因鉴定
    利用建立的临床队列和生物样品,应用高通量遗传筛选技术及分子生物学技术,鉴定致病基因和风险基因。对有明显家族发病倾向的神经系统疾病,采用三代基因测序、全基因组测序、全外显子测序、拷贝数变异(CNV)分析等高通量技术进行遗传筛选,获得海量数据,利用生物信息数据分析软件分析数据,锁定目标基因后,采用Sanger 测序、重复引物PCR(TP-PCR)技术、多重连接探针扩增(MLPA)技术等确认目标基因,进一步采用单体型连锁分析方法进行家系共分离分析,正常对照验证,蛋白功能预测,从而鉴定出新致病基因。对无家族发病倾向的复杂性疾病(complex disease),采用全基因组关联分析等高通量遗传筛选技术筛选新的风险基因,分析多个风险基因的协同作用,评估发病风险。汇总基因变异谱和临床表型谱,建立具有中国特色和国际标准的神经系统疾病数据库及网络共享平台。
    2、神经系统疾病的致病机理研究
    针对新致病基因和风险基因,利用条件性点突变、组织特异性可逆打靶、多基因敲低等基因编辑技术,构建致病基因敲入、敲除、点突变或多基因敲低的疾病小鼠模型;构建携带基因变异的人源ES和患者来源的iPS细胞模型;鉴定疾病模型的表型并应用动物行为学、神经环路示踪、神经元荧光活体标记和成像、分子和细胞生物学等技术,研究神经系统疾病的遗传机制、分子细胞机制和神经环路机制,挖掘潜在的治疗靶点。
    3、神经系统疾病的精准诊治研究
    利用建立的临床数据库、生物样品库和基因变异数据库,结合疾病模型及致病机理研究结果,应用基因组学、蛋白质组学、脂质组学等多种组学技术,联合分子影像及强磁场结构与功能磁共振成像,挖掘具有诊断和预警价值的标志物及干预靶点,研发可推广应用的简便快速准确的诊断试剂盒,结合临床诊疗数据,优化神经系统疾病的精准诊治流程,制定可推广应用的精准诊治策略。

    代表性论文

    Dong HL, Cheng HL, Bai G, Shen Y, Wu ZY*. Novel GDAP2 pathogenic variants cause autosomal recessive spinocerebellar ataxia-27 (SCAR27) in a Chinese family. Brain, 2020 (in press) 

    Li XY, Li HL, Dong Y, Gao B, Cheng HR, Ni W, Gan SR, Liu ZJ, Burgunder JM, Wu ZY*. Haplotype analysis encompassing HTT gene in Chinese patients with Huntington's disease. Eur J Neurol. 2020,27(2):273-279 

    Li QF#, Dong Y#, Yang L#, Xie JJ, Ma Y, Du YC, Cheng HL, Ni W, Wu ZY*.Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3. Mol Neurodegener. 2019,14(1):39. 

    Wei Q#, Dong HL#, Pan LY#, Chen CX, Yan YT, Wang RM, Li HF, Liu ZJ, Tao QQ*, Wu ZY*. Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia. Transl Neurodegener. 2019, 8:19. 

    Liu ZJ#, Lin HX#, Wei Q#, Zhang QJ#, Chen CX, Tao QQ, Liu GL, Ni W, Gitler AD, Li HF*, Wu ZY*. Genetic Spectrum and Variability in Chinese Patients with Amyotrophic Lateral Sclerosis. Aging Dis 2019; 10(6):1199-1206. 

    Li HL#, Li XY#, Dong Y#, Zhang YB, Cheng HR, Gan SR, Liu ZJ, Ni W, Burgunder JM, Yang XW, Wu ZY*. Clinical and genetic profiles in Chinese patients with Huntington’s disease: a ten-year multicenter study in China. Aging Dis 2019;10(5):1003-1011. 

    Chen CX#, Dong HL#, Wei Q#, Li LX, Yu H, Li JQ, Liu GL, Li HF, Bai G, Ma H, Wu ZY*. Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease. Clin Genet 2019; 96: 439-448. 

    Li JQ#, Dong HL#, Chen CX, Wu ZY*. A novel WARS mutation causes distal hereditary motor neuropathy in a Chinese family. Brain 2019; 142: 1-4(e49). 

    Li XY#, Zhang YB#, Xu M#, Cheng HR, Dong Y, Ni W, Li HL*, Wu ZY*. Effect of apolipoprotein E genotypes on Huntington's disease phenotypes in a Han Chinese population. Neurosci Bull 2019, 35(4): 756-762. 

    Chen YC#, Yu H#, Wang RM#, Xie JJ, Ni W, Zhang Y, Dong Y*, Wu ZY*. Contribution of intragenic deletions to mutation spectrum in Chinese patients with Wilson's disease and possible mechanism underlying ATP7B gross deletions. Parkinsonism Relat Disord 2019; 62:128-133. 

    Li HF#, Yang L#, Yin D#, Chen WJ, Liu GL, Ni W, Wang N, Yu W, Wu ZY*, Wang Z*. Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia. Parkinsonism Relat Disord 2019; 62:134-140. 

    Jiang B#, Zhou J#, Li HL#, Chen YG#, Cheng HR, Ye LQ, Liu DS, Chen DF, Tao QQ*, Wu ZY*. Mutation screening in Chinese patients with familial Alzheimer's disease by whole-exome sequencing. Neurobiol Aging 2019; 76: 215.e15-215.e21. 

    Lu C#, Li LX#, Dong HL#, Wei Q, Liu ZJ, Ni W, Gitler4 AD, Wu ZY*. Targeted next-generation sequencing improves diagnosis of hereditary spastic paraplegia in Chinese patients. J Mol Med, 2018, 96: 701-712. 

    Chen YJ, Dong HL, Li LX, Ni W, Li HF*, Wu ZY*. Novel PLA2G6 mutations and clinical heterogeneity in Chinese cases with phospholipase A2-associated neurodegeneration. Parkinson Relat Disord, 2018, 49:88-94. 

    Tan GH#, Liu YY#, Wang Lu#, Li K#, Zhang ZQ, Li HF, Zhang ZF, Li Y, Li D, Wu MY, Yu CL, Long JJ, Chen RC, Li LX, Yin LP, Liu JW, Cheng XW, Shen Q, Shu YS, Sakimura K, Liao LJ§, Wu ZY§, Xiong ZQ*. PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res, 2018, 28: 90-110. (§Senior author) 

    Li LX, Liu GL, Liu ZJ, Lu C, Wu ZY*. Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D (CMT4D). Hum Mutat, 2017, 38(11): 1569-1578. (封面论文) 

    Liu ZJ, Lin HX, Liu GL, Tai QQ, Ni W, Xiao BG, Wu ZY*. The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis. Clin Genet, 2017, 92(3): 267-273. 

    Tao QQ#, Liu ZJ#, Sun YM#, Li HL, Yang P, Liu DS, Jiang B, Li XY, Xu JF, Wu ZY*. Decreased gene expression of CD2AP in Chinese patients with sporadic Alzheimer’s disease. Neurobiol Aging, 2017, 56: 212.e1-e10. 

    Li HF, Liu ZJ, Dong HL, Xie JJ, Zhao SY, Ni W, Dong Y, Wu ZY*. Clinical features of Chinese patients with Gerstmann-Str?ussler-Scheinker identified by targeted next-generation sequencing. Neurobiol Aging, 2017, 49: 216.e1-e5 

    Dong Y#, Ni W#, Chen WJ#, Wan B#, Zhao GX, Shi Z, Zhang Y, Wang N, Yu L, Xu J, Wu ZY*. Spectrum and classification of ATP7B variants in a large cohort of Chinese patients with Wilson’s disease guides genetic diagnosis. Theranostics, 2016, 6(5): 638-649. 

    Su P#, Chen S#, Zheng YH#, Zhou HY, Yan CH, Yu F, Zhang YG, He L, Zhang Y, Wang Y, Wu L, Wu X, Yu B, Ma LY, Yang Z, Wang J, Zhao G, Zhu J*, Wu ZY*, Sun B*. Novel function of extracellular matrix protein 1 in suppressing Th17 cell development in experimental autoimmune encephalomyelitis. J Immunol, 2016, 197(4): 1054-1064. 

    Liu Y, Su Q, Chen M, Dong Yi, Shi Y, Feng W, Wu ZY, Li F. Near-infrared upconversion chemodosimeter for in vivo detection of Cu2+ in Wilson disease. Advanced Materials (ADV Meter), 2016, 28: 6625-6630. 

    Yao Y#, Cui X#, Al-Ramahi I#, Sun X#, Li B, Hou J, Difiglia M, Palacino J, Wu ZY*,Ma L*, Botas J*, Lu B*. A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity. Elife, 2015; 4: e05449. 

    Cheng Q#, He SQ#, Gao D, Lei B, Long X, Liang HF, Zhu P, Jin JF, Tang B, Tomlinson S, Wu ZY*, Chen XP*. Early Application of Auxiliary Partial Orthotopic Liver Transplantation in Murine Model of Wilson Disease. Transplantation, 2015, 99 (11): 2317-2324. 

    Lu HP#, Gan SR#, Chen S#, Li HF, Liu ZJ, Ni W, Wang N, Wu ZY*. Intermediate-length polyglutamine in ATXN2 is a possible risk factor among Eastern Chinese patients with amyotrophic lateral sclerosis. Neurobiol Aging, 2015, 36(3): 1603.e11-14. 

    Dong Y, Wu JJ, Wu ZY*. Identification of 46 CAG repeats within PPP2R2B as probably the shortest pathogenic allele for SCA12. Parkinsonism Relat Disord, 2015, 21(4): 398-401. 

    Liu ZJ#, Li HF#, Tan GH#, Tao QQ, Ni W, Cheng XW, Xiong ZQ, Wu ZY*. Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system. Neurobiol Aging, 2014, 35(12):2881.e11-15. 

    Jiang H#, Sun YM#, Hao Y, Yan YP, Chen K, Xin SH, Tang YP, Li XH, Jun T, Chen YY, Liu ZJ, Wang CR, Li H, Pei Z, Shang HF, Zhang BR, Gu WH, Wu ZY*, Tang BS, Burgunder JM*, Chinese HD Network. Huntingtin gene CAG repeat numbers in Chinese patients with Huntington's disease and controls. Eur J Neurol, 2014, 21(4):637-642. 

    Liu ZJ#, Sun YM#, Ni W, Dong Y, Shi SS, Wu ZY*. Clinical features of Chinese patients with Huntington’s disease carrying CAG repeats beyond 60 within HTT gene. Clin Genet, 2014, 85:189-193. 

    Zhu M, Tao Y, He Q, Gao H, Song F, Sun YM, Li HL, Wu ZY*, David Saffen*. A common GSAP promoter variant contributes to Alzheimer’s disease liability. Neurobiol Aging, 2014, 35(11): 2656.e1-7. 

    Tao QQ, Sun YM, Liu ZJ, Yang P, Li HL, Lu SJ, Wu ZY*. Lack of association between CALHM1 p.P86L variation and Alzheimer's disease in the Han Chinese population. Neurobiol Aging, 2014, 35(8):1956.e13-14.  

    Lu SJ#, Li HL#, Sun YM, Liu ZJ, Yang P, Wu ZY*. Clusterin variants are not associated with southern Chinese patients with Alzheimer's disease. Neurobiol Aging, 2014, 35(11): 2656.e9-11. 

    Liu QB, Li ZX, Zhao GX, Yu H, Wu ZY*. No association between the identified multiple sclerosis non-MHC risk loci and neuromyelitis optica. Neurosci Bull, 2014, 30(6):1036-1044. 

    Li HF#, Chen WJ#, Ni W, Wu ZY*. Paroxysmal kinesigenic dyskinesia and myotonia congenita in the same family: coexistence of a PRRT2 mutation and two CLCN1 mutations. Neurosci Bull, 2014, 30(6): 1010-1016. 

    Li HF, Chen WJ, Ni W, Wang KY, Liu GL, Wang N, Xiong ZQ, Xu J, Wu ZY*. PRRT2 mutation correlated with phenotype of paroxysmal kinesigenic dyskinesia and drug response. Neurology, 2013, 80(16):1534-1535. 

    Dong Y#, Sun YM#, Liu ZJ, Ni W, Shi SS, Wu ZY*. Chinese patients with Huntington’s disease initially presenting with spinocerebellar ataxia. Clin Genet, 2013, 83(4):380-383. 

    Zhao GX#, Liu Y#, Li ZX, Lv CZ, Traboulsee A, Sadovnick AD, Wu ZY*. Variants in the promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Han Chinese population. Neurosci Bull, 2013, 2013, 29(5): 525-530. 

    Chen WJ, Lin Yu, Xiong ZQ, Wei W, Ni W, Tan GH, Guo SL, He J, Chen YF, Zhang QJ, Li HF, Lin Yi, Murong SX, Xu J, Wang N*, Wu ZY*. Exome sequencing identifies truncating mutations in the PRRT2 gene that cause paroxysmal kinesigenic dyskinesia. Nat Genet, 2011, 43(12): 1252-1255. 

    Wang ZQ, Chen XJ, Murong SX, Wang N, Wu ZY*. Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A. J Mol Med, 2011, 89(6): 569-576. 

    Cai B, Lin Y, Xue XH, Fang L, Wang N*, Wu ZY*. TAT-mediated delivery of neuroglobin protects against focal cerebral ischemia in mice. Exp Neurol, 2011, 227(1): 224-231.

    Wang N, Xue XH, Lin Y, Fang L, Murong SX, Wu ZY*. The R219K polymorphism in the ATP-binding cassette transporter 1 gene has a protective effect on atherothrombotic cerebral infarction in Chinese Han ethnic population. Neurobiol Aging, 2010, 31(4): 647-653. 

    Xu H#, Wu ZY#, Fang F, Guo L, Chen D, Xi Chen J, Stern D, Taylor GA, Jiang H, Shidu Yan S. Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells. FASEB J, 2010, 24(5):1583-1592. (#Co-first) 

    Gan SR#, Zhao K#, Wu ZY*, Wang N, Murong SX. Chinese patients with Machado-Joseph disease presenting with complicated hereditary spastic paraplegia. Eur J Neurol, 2009, 16(8):953-956. 

    Wu ZY*, Lin Y, Chen WJ, Zhao GX, Xie H, Murong SX, Wang N. Molecular analyses of GCH-1, TH and parkin genes in Chinese dopa- responsive dystonia families. Clin Genet, 2008, 74(6): 513-521. 

    Chen WJ#, Wu ZY#, Lin MT, Su JF, Lin Y, Murong SX, Wang N*. Molecular analysis and prenatal prediction of spinal muscular atrophy in Chinese patients by the combination of restriction fragment length polymorphism analysis, denaturing high-performance liquid chromatography, and linkage analysis. Arch Neurol, 2007, 64(2): 225-231. (#Co-first) 

    Wu ZY*, Zhao GX, Chen WJ,Wang N, Wan B, Lin MT, Murong SX, Yu L. Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease. J Mol Med, 2006, 84(5): 438-442. 

    Wu ZY*, Wang ZQ, Murong SX, Wang N*. FSHD in Chinese population: Characteristics of translocation and genotype-phenotype correlation. Neurology, 2004, 63(3): 581-583. 

    Wu ZY*, Lin MT, Murong SX, Wang N*. Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease. Arch Neurol (2015年更名为JAMA Neurology), 2003, 60(5): 737-741. 

    Yan SS, Wu ZY, Zhang HP, Furtado G, Chen X, Yan SF, Schmidt AM, Brown C, Stern A, LaFailie J, Chess L, Stern D, Jiang H. Suppressipn of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat Med, 2003, 9(3): 287-293. 

    Wu ZY*, Wang N, Lin MT, Fang L, Murong SX. Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in Chinese patients with Wilson disease. Arch Neurol (2015年更名为JAMA Neurology), 2001, 58 (6): 971-976.

    实验室网址:https://person.zju.edu.cn/wuzhiying/
    E-mail: zhiyingwu@zju.edu.cn
    电话:0571-87783695