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基本信息:

姓名: 管敏鑫
职务: PI
职称: 教授
学历: 博士
专业: 人类遗传学
所属院系: 遗传学研究所
研究方向: 线粒体遗传学和母系遗传性疾病基础研究及临床转化
电话: 0571-88206497
信箱: gminxin88@zju.edu.cn
个人主页: http://mypage.zju.edu.cn/guanmx

个人简介:

学术团体和社会兼职:

中国人民解放军总医院/军医进修学院客座教授(2002-至今)

美国辛辛那提大学儿童医院医学中心客座教授 (2011.10-至今)

浙江省医学遗传学重点实验室学术委员会主任(2005-至今)

第四届亚洲线粒体研究与医学学会(ASMRM)主席(2011-2014 

中国遗传学会常务理事2014-至今)

中国遗传学会国际交流委员会主任委员(2014-至今)

 

学历和研究经历:

1979.9-1983.7   杭州大学(现浙江大学)生物系本科

1983.8-1989.9   浙江图书馆  馆员

1989.10-1993.7 澳大利亚国立大学生物化学与分子生物学博士研究生

1993.8-1996.7   加州理工学院生物系人类分子遗传学 Research Fellow

1996.8-1999.7   加州理工学院生物系 Senior Research Fellow

1999.8-2011.9   辛辛那提大学儿童医院医学中心人类遗传学助理教授、副教授、教授

2011.1-2013.11 浙江大学生命科学学院   院长

2011.1-2015.2   浙江大学生命科学学院教授遗传学研究所所长

2015.3-至今     浙江大学医学院/生命科学学院教授遗传学研究所所长

工作研究领域

 

 国家“千人计划”特聘专家,"973"计划项目首席科学家。长期从事线粒体遗传学和母系遗传性疾病的基础研究和临床转化。作为PI,曾经获得5项美国国立卫生研究院(NIH)基金资助。自2011年全职回国后,主持国家重点基础研究发展计划(973计划),“十二五”国家科技支撑计划,国家自然科学基金重点项目等多项课题。已在母系遗传性聋病、高血压和Leber遗传性视神经病变致病机理和tRNA转录后修饰的机制等领域发表论文共174篇,其中在Cell Am J Hum GenetHum Mol GenetCirculation ResearchOphthalmology等本领域国际权威学术期刊上发表SCI论文100多篇。曾获国家科技进步二等奖、谈家桢生物科学创新奖等多项奖励。主编出版《医学遗传学》等教材。

 

在研的主要项目: 

1. 国家重点基础研究发展计划(973计划): 单基因遗传性聋病的分子机制研究, 2014.1-2018.12

2. 国家自然科学基金重点项目:核修饰基因调控母系遗传性耳聋发病机制及听觉功能重建的策略研究,2014.1-2017.12

3. 十二五支撑项目:Leber遗传性视神经病变的分子诊断和治疗研究,2012.1-2015.12

 

专利及代表性论文(*corresponding authors)

 

国家发明专利:

用于同时检测线粒体DNA A1555G和C1494T突变的试剂盒及其使用方法.申请号:200910223263.8

 

耳聋遗传

Guan, M.X., Fischel-Ghodsian, N., Attardi, G. (1996) Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation. Hum. Mol. Genet. 5:963-972.

Guan, M.X., Enriquez, J.A., Fischel-Ghodsian, N., Puranam, R., Lin, C.P., Marion, M.A., Attardi, G. (1998) The Deafness-associated mtDNA 7445 mutation, which affects tRNASer(UCN) precursor processing, has long-range effects on NADH dehydrogenase ND6 subunit gene expression. Mol. Cell. Biol.18:5868-5879.

*Guan, M.X, Fischel-Ghodsian, N., Attardi,G. (2000) A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity. Hum. Mol. Genet. 9: 1787-1793.

*Guan, M.X., Fischel-Ghodsian, N., Attardi,G. (2001) Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation. Hum. Mol. Genet.10: 573-580.

Li, X., Fischel-Ghodsian,N., Schwartz, F., Yan, Q., Friedman, R.A., *Guan, M.X.(2004) Biochemical characterization of the mitochondrial tRNAT7511C mutation associated with nonsyndromic deafness. Nucleic Acids Res.32: 867-877.

Zhao, H., Li, R., Wang, Q., Yan, Q., Deng, J.H., Han, D., Bai, Y., Young, W.Y., *Guan, M.X. (2004) Maternally inherited aminoglycoside-induced and non-syndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. Am. J. Hum. Genet.74:139-152.

Li, R., Greinwald, J.H., Yang, L., Choo, D.I., Wenstrup, R.J.,*Guan, M.X.(2004) Molecular analysis of mitochondrial 12S rRNA and tRNA genes in pediatric subjects with nonsyndromic hearing loss. J. Med. Genet. 41:615-620.

Li, Z., Li, R., Chen, J., Liao, Z.,Zhu,Y., Qian,Y., Xiong,S., Heman-Ackah,S., Wu, J., Choo, D.I., *Guan, M.-X. (2005)Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside induced and non-syndromic hearing loss. Hum. Genet.117:9-15.

Zhao, H., Young, W.Y., Yan, Q., Li, R., Cao, J., Wang, Q., Li, X., Peters, J.L., Han, D., *Guan, M.X.(2005) Functional characterization of the mitochondrial 12S rRNA C1494T mutation associated with aminoglycoside-induced and nonsyndromic hearing loss. Nucleic Acid Res. 33:1132-1139.

*Guan, M.X, Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, M., Suzuki, T., del Castillo, I., Peters, J.L., Li, R., Qian, Y., Wang, X., Ballana, E., M. Shohat, Lu, J., Estivill, X., Watanabe, K., Fischel-Ghodsian, N. (2006) Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations. Am. J. Hum. Genet.79:291-302.

Qian Y,*Guan MX.(2009) Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness-associated mutation. Antimicrob Agents Chemother. 53:4612-4618.

*Guan, M.X. (2011) Mitochondrial 12S rRNA Mutations associated with aminoglycoside ototoxicity. Mitochondrion. 11: 237-245.

Yan X, Wang X, Wang Z, Sun S, Chen G, He Y, Mo JQ, Li R, Jiang P, Lin Q, Sun M, Li W, Bai Y, Zhang J, Zhu Y, Lu J, Yan Q, Li H, *Guan MX. (2011)Maternally transmitted late-onset non-syndromic deafness is associated with the novel heteroplasmic T12201C mutation in the mitochondrial tRNAHis gene. J Med Genet. 48:682-90.

Raimundo N, Song, L, Shutt TE, McKay SE, Cotney J, Guan MX, Gilliland TC, Hohuan, D, Santos-Sacchi S, Shadel GS. (2012) Mitochondrial Stress Engages E2F1Apoptotic Signaling to Cause Deafness. Cell. 148, 716-726.

Zheng J, Ji Y, *Guan, M.X. (2012) Mitochondrial tRNA mutations associated with deafness. Mitochondrion. 12:406-13.

Gong, S., Peng, Y., Jiang, P., Wang, M., Fan, M., Wang, X., Zhou, H., Li, H., Yan, Q., Huang, T., *Guan, M.X (2014) A deafness-associated tRNAHis mutation alters the mitochondrial function, ROS production and membrane potential. Nucleic Acids Res. 42:8039-48.

 

Leber遗传性视神经病变

Qu,J., Li,R., Tong,Y., Zhou,X., Lu,F., Qian,Y., Hu,Y., Mo, J.Q., West, C.E., *Guan, M.X. (2006) The novel A4435G mutation in the mitochondrial tRNAMet may modulate the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family. Invest. Ophth. Vis. Sci. 47:475-83.

Qu, J., Zhou, X., Zhang, J., Zhao, F., Sun, Y.H., Yong, Y., Wei, Q.P., Cai, W., West, C.E., *Guan, M.X. (2009) Extremely low penetrance of Leber’s hereditary optic neuropathy in eight Han Chinese families carrying the ND4 G11778A mutation. Ophthalmology.16:558-564.

Qu J, Wang Y, Tong Y, Zhou X, Zhao F, Yang L, Zhang S, Zhang J, West CE,*Guan MX.(2010) Leber's hereditary optic neuropathy affects only female matrilineal relatives in two Chinese families. Invest Ophthalmol Vis Sci. 51:4906-4912.

Liu XL, Zhou T, Zhou J, Zhao F, Zhang J, Li C, Ji Y, Zhang Y, Wei QP,Sun YH, Yang L, Lin B, Yuan Y, Li Y, Qu J, *Guan MX (2011) Leber’s hereditary optic neuropathy is associated with the novel T12338C mutation in mitochondrial ND5 gene in six Han Chinese families. Ophthalmology. 118:978-985.

Zhou X, Qian Y, Zhang J, Tong Y, Jiang P, Liang M, Dai X, Zhou H, Zhao F, Ji Y, Mo JQ, Qu J, *Guan MX (2012) Leber's Hereditary Optic Neuropathy Is Associated with the T3866C Mutation in Mitochondrial ND1 Gene in Three Han Chinese Families. Invest Ophthalmol Vis Sci. 53:4586-4594.

Liang M, Jiang P, Li F, Zhang J, Ji Y, He Y, Xu M, Zhu J, Meng X, Zhao F, Tong Y, Liu X, Sun Y, Zhou X, Mo JQ, Qu J, *Guan MX (2014) Frequency and spectrum of mitochondrial ND6 mutations in 1218 Han Chinese subjects with Leber's hereditary optic neuropathy. Invest Ophthalmol Vis Sci 55:1321-31.

 

原发性高血压

Liu, Y., Li, R., Li, Z., Wang, X., Yang, L., Wang, S., *Guan, M.X.(2009).The mitochondrial tRNAMet 4435A>G mutation is associated with maternally inherited hypertension in a Chinese pedigree. Hypertension. 53:1083-1090.

Li, R., Liu, Y., Li, Z., Yang, L., Wang, S., *Guan, M.X. (2009) Failures in mitochondrial tRNAMet and tRNAGln metabolism caused by the novel 4401A>G mutation are involved in essential hypertension in a Han Chinese family. Hypertension 54:329-337.

Wang S, Li R, Fettermann A, Li Z, Liu Y, Wang X, Zhou A, Yang L, Taschner A, Rossmanit W, *Guan MX. (2011) Maternally inherited essential hypertension is associated with the novel 4263A>G mutation in the mitochondrial tRNAIle gene in a large Han Chinese family. Circulation Res. 108:862-870.

Lu Z, Chen H, Meng Y, Wang Y, Xue L, Zhi S, Qiu Q, Yang L, Mo JQ,*Guan MX. (2011) The tRNAMet 4435A>G mutation in the mitochondrial haplogroup G2a1 is responsible for maternally inherited hypertension in a Chinese pedigree. Eur J Hum Genet. 19(11):1181-6.

Chen H, Zheng J, Xue L, Meng Y, Wang Y, Zheng B, Fang F, Shi S, Qiu Q, Jiang P, Lu Z, Mo JQ, Lu J, *Guan MX (2012) The 12S rRNA A1555G mutation in the mitochondrial haplogroup D5a is responsible for maternally inherited hypertension and hearing loss in two Chinese pedigrees. Eur J Hum Genet. 20(6):607-12.

Qiu Q, Li R, Jiang P, Xue L, Lu Y, Song Y, Han J, Lu Z, Zhi S, Mo JQ, *Guan MX (2012)Mitochondrial tRNA mutations are associated with maternally inherited hypertension in two Han Chinese pedigrees. Hum Mutat. 33(8):1285-93

Jia Z, Wang X, Qin Y, Xue L, Jiang P, Meng Y, Shi S, Wang Y, Qin Mo J, *Guan MX (2013) Coronary heart disease is associated with a mutation in mitochondrial tRNA. Hum Mol Genet. 22:4064-73

Qin, Y., Xue, L., Jiang, P., Xu, M., He, Y., Shi, S., Huang, Y., He, J., Mo, J.Q., *Guan MX (2014) Mitochondrial tRNA variants in Chinese subjects with coronary heart disease. J Am Heart Assoc. 3:e000437

 

线粒体tRNA碱基修饰机制

Li, X., Li,R., Lin,X.,*Guan,M.X.(2002) Isolation and characterization of the putative nuclear modifier gene MTO1 involved in the pathogenesis of deafness-associated mitochondrial 12S rRNA A1555G mutation. J. Biol. Chem. 277:27256-27264.

Li, X.,*Guan, M.X.(2002) A human mitochondrial GTP binding protein related to tRNA modification may modulate the phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation. Mol. Cell. Biol.22:7701-7711.

Yan, Q., Li, X., Faye, G. and *Guan, M.X. (2005) Mutations in MTO2 related to tRNA modification impair mitochondrial gene expression and protein synthesis in the presence of a paromomycin resistance mutation in mitochondrial 15S rRNA. J. Biol. Chem. 280: 29151-29157.

*Guan, M.X, Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, M., Suzuki, T., del Castillo, I., Peters, J.L., Li, R., Qian, Y., Wang, X., Ballana, E., M. Shohat, Lu, J., Estivill, X., Watanabe, K., Fischel-Ghodsian, N. (2006) Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations. Am. J. Hum. Genet.79:291-302.

Wang X, Yan Q,*Guan MX. (2010) Combination of the loss of cmnm5U34 with the lack of s2U34 modifications of tRNA, tRNA, and tRNAaltered mitochondrial biogenesis and respiration. J Mol Biol.395:1038-1048.

Li R, *Guan MX. (2010) Human mitochondrial leucyl-tRNA synthetase correctes mitochondrial dysfunctions due to the MELAS and diabetes associated tRNALeu(UUR) A3243G mutation. Mol Cell Biol. 30:2147-54.