李曉江

李曉江教授致力於研究早期神經系統發育、衰老與神經退行性疾病，利用轉基因疾病動物（鼠，豬，猴）模型揭示與神經系統發育的重要基因和基因變異如何引起與衰老有關的蛋白構像異常與神經細胞死亡。研究成果發表於《Cell》《Nature》等國際核心刊物200篇，研究論文累計引用率達到27150餘次， H-index 為 86。 ^[2] 

1977-1982年，江西醫學院醫學專業學士

1983-1986年，蘇州醫學院藥理學碩士

1987-1991年，美國Oregon Health Science University 藥理學博士

1991-1995年，美國Johns Hopkins University 神經學科博士後

1995-1996年，美國Johns Hopkins University精神病學系助理教授

1996-2001年，美國Emory大學人類遺傳學系助理教授

2001-2005年，美國Emory大學人類遺傳學系終身副教授

2005年起，美國Emory大學人類遺傳學系終身教授

2007年起，美國Emory大學Distinguished Professor of Human Genetics (傑出講席教授)

2008年起，華中科技大學基礎醫學院講座教授 ^[1] 

2019年全職加盟暨南大學，任暨南大學粵港澳中樞神經再生研究院教授。 ^[2] 

1．遺傳性神經退行性疾病的病理機制研究。

2．細胞內轉運與早期神經系統的發育。

李曉江教授是國際著名神經退行性疾病研究專家，於2008年與合作者在世界上首次利用轉基因方法建立了非人靈長類的亨廷頓疾病模型。2015年製備出首例帕金森病的轉基因猴模型，並利用CRISPR/Cas9技術製備了首例杜氏肌營養不良症及自閉症猴模型。2018年建立的世界首例亨廷頓基因敲入豬模型的研究成果發表在國際頂級期刊《Cell》雜誌。研究成果發表於Cell, Nature, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, J Clin Invest, Cell Stem Cell, Cell Research, PNAS, J Cell Biol, J Neurosci等國際核心刊物180篇，研究論文總影響因子（IF）達1388，H-index為63，累計引用率近15000次。 ^[4] 

Bhat KP, Yan S, Wang CE, Li SH, Li X-J. Differential ubiquitination and degradation of huntingtin fragments modulated by E3 ligase Ube3a. Proc Natl Acad Sci U S A, 2014; published ahead of print March 31, 2014, doi:10.1073/pnas.1402215111

Yang HQ, Wang GH, Sun HT, Shu RZ, Liu T, Wang CE, Liu ZM, Zhao Y, Zhen QY, Yang DS, Huang J, Zhou YL, Li SH, Jiang XD, Xiao ZC, Li X-J*, Lai LX. Species-dependent neuropathology in transgenic SOD1 pigs. Cell Res 2014 Feb 28. doi: 10.1038/cr.2014.25. [Epub ahead of print] (*Corresponding author)

Yan S, Wang CE, Wei W, Gaertig MA, Lai L, Li S, Li X-J. TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain. Hum Mol Genet. 2014 Jan 10. [Epub ahead of print]

Su Y, Huang SS, Gaertig MA,Li X-J*, Li SH. Age-dependent decrease in chaperone activity impairs MANF expression leading to Purkinje cell degeneration in inducible SCA17 mice. Neuron, 81, 349–365 2014 (*Corresponding author)

Xiang JX, Yang H, Zhao T, Sun M, Xu XS, Zhou X.F., Li SH, Li X-J. Huntingtin-Associated Protein 1 is essential for postnatal growth by regulating neurogenesis. J Clin Invest. 124(1):85-98. 2014

Xu Q.Q., Huang S.S., Song M.K., Wang C.E. Yan S., Liu X.D., Gaertig M.A., Yu. S.P., Li H., Li S.H., Li X-J. Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms. J. Cell Biol. 202:1123-1138, 2013.

Weng L, Lin YF, Li AL, Wang CE, Yan S, Sun M, Gaertig MA, Mitha N, Kosaka J, Wakabayashi T, Xu X, Tang B, Li S, Li XJ. Loss of Ahi1 affects early development by impairing BM88/Cend1-mediated neuronal differentiation. J Neurosci. 33:8172-84. 2013.

Cape A, Chen XX, Wang CE, O’Neill A, Lin YF, He J, Xu XS, Yi H, Li H, Li SH, Li X-J. Loss of huntingtin-associated protein 1 impairs insulin secretion from pancreatic beta cells. Cell Mol Life Sci, 69:1305-17. 2012.

Wang H, Huang Z, Huang L, Niu S, Rao X, Xu J, Kong H, Yang J, Yang C, Wu D, Li S, Li XJ, Liu T, Sheng G. Hypothalamic Ahi1 mediates feeding behavior through interaction with 5-HT2C receptor. J Biol Chem. 287(3):2237-46. 2012

Mandal M, Wei J, Zhong P, Chen J, Duffney LJ, Liu W, Yuen EY, Twelvetrees AE, Li S, Li XJ, Kittler JT, Yan Z. Impaired AMPA receptor trafficking and function by mutant Huntingtin. J Biol Chem. 286:33719-28. 2011.

Huang SS, Ling JJ, Yang S. Li X-J*, Li SH. Neuronal expression of TATA box binding protein containing expanded polylgutamine in knock-in mice reduces chaperone protein response by impairing the function of NF-Y transcription factor. Brain 134(Pt 7):1943-58, 2011 (*Corresponding author)

Havel LS, Wang CE, Huang B, Wade B, Li SH, Li X-J. Preferential localization of N-terminal mutant huntingtin in striatal neurons cause neurological symptoms and is regulated by phosphorylation. Hum Mol Genet. 20:1424-37, 2011

Xu XS, Yang H, Lin Y.F., Li X, Cape A, Ressler KJ, Li SH, Li X-J. Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype.Proc Natl Acad Sci U S A. 107:19126-31, 2010

Yang DS, Wang CE, Zhao BT, Li W, Quyan Z, Liu ZM, Yang HQ, O’Neill A, Yi H, Li SH, Lai LX, Li X-J. Expression of Huntington disease protein results in apoptotic neurons in the brains of cloned transgenic pigs. Hum. Mol. Genet, 19:3983-94, 2010

Lin YF, Xu XS, Cape A, Li SH, Li XJ. Hap1 deficiency in orexin-producing neurons impairs neuronal process extension and leads to abnormal behavior in mice. J Biol Chem. 285:15941-9, 2010.

Bradford J, Shin J-Y, Roberts M, Wang C-E, Sheng G-Q, Li SH, Li X-J. Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. J Biol Chem. 285:10653-61, 2010.

Bradford J, Shin J-Y, Roberts M, Wang C-E, Li X-J, Li SH. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci USA. 106:22480-5,

Friedman MJ, Li S, Li X-J. Activation of gene transcription by heat shock protein 27 may contribute to its neuronal protection. J Biol Chem. 284:27944-51, 2009

Orr AG, Orr AL, Li X-J, Gross RE, Traynelis SF. Adenosine A2A receptor mediates microglial process retraction. Nature Neurosci. 12:872-8, 2009.

Shah A, Freidman M. Huang SS, Roberts M, Li X-J, Li SH Transcriptional dysregulation of TrkA associates with neurodegeneration in spinocerebellar ataxia type 17. Hum Mol Genet. 18: 4141-52, 2009.

Tydlacka S, Wang CE, Wang XJ, Li SH, Li X-J. Differential activities of the ubiquitin-proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons. J. Neurosci. 28: 13285-13295, 2008

Wang CE, Tydlacka S, Adam OL, Yang SH, Graham RK, Hayden MR, Li SH, Chan AW, Li X-J. Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington’s disease. Hum. Mol. Genet. 17: 2738-2751, 2008

Sheng GQ, Xu XS, Lin YF, Wang CE, Rong J, Peng J, Jiang X, Li SH, Li X-J. Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. J Clin Invest 118:2785-95, 2008

Wang CE, Zhou H, McGuire JR, Cerullo V, Lee B, Li SH, Li X-J. Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J. Cell Biol. 181: 803-816, 2008

Orr AL, Huang SS, Robert MA, Reed JC, Li SH, Li X-J. Sex-dependent effect of BAG1 in ameliorating motor deficits of huntington’s disease transgenic mice. J. Biol. Chem. 283:16027-36, 2008

Yang SH, Cheng PH, Banta H, Piotrowska-Nitsche K, Yang JJ, Larkin K, Snyder B, Cheng ECH, Liu J, Orkin J, Fang ZH, Smith Y, Bachevalier J, Zola SM, Li SH, Li X-J, Chang AWS. Toward a transgenic model of Huntington’s disease in a non-human primate. Nature 453: 921-924, 2008

Orr AL, Li SH, Wang CE, Li H, Rong J, Xu XS, Mastroberardino PJ, Greenamyre TJ, Li X-J. N-terminal Mutant Huntingtin Associates with Mitochondria Directly and Disrupts the Interaction of Mitochondria with Trafficking Proteins. J. Neurosci. 28: 2783-92, 2008

Wang JJ, Wang CE, Orr A, Tydlacka S, Li SH, Li X-J. Impaired ubiquitin-proteasome system activity in the synapses of Huntington disease mice. J. Cell Biol. 180: 1177-89, 2008.

Friedman MJ, Wang CE, Li XJ, Li SH. Polyglutamine expansion reduces the association of TBP with DNA and induces DNA binding-independent neurotoxicity. J Biol Chem. 283: 8283-90, 2008

Metzger S, Rong J, Nguyen HP, Cape A, Tomiuk J, Soehn A, Propping P, Freudenberg-Hua Y, Freudenberg J, Tong L, Li SH, Li XJ*, Riess O. Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease. Hum Mol Genet. 17: 1137-46, 2008 (*Corresponding author)

Friedman M., Fang ZH., Shah A., Goursac L., Warren S., Li SH., Li X-J. Polyglutamine domain regulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nature Neuroscience 10: 1519-28, 2007

重慶醫科大學腦科學與腦疾病研究院學術顧問委員會 ^[4] 

由於SHANK3基因突變也可以導致自閉症。李曉江團隊與張永清團隊早在2017年就利用CRISPR/Cas9技術建立了世界首例SHANK3基因編輯的自閉症猴模型，並且發現SHANK3可特異性調控靈長類胚胎大腦發育。而本研究中關於CHD8基因突變猴模型的發現再次證實了利用非人靈長類動物模型研究自閉症病理機制的必要性和不可取代性。 ^[3]