tutor
导师介绍
李学坤
教授|博士生导师
浙江大学转化医学研究院
xuekun_li@zju.edu.cn
浙江省杭州市江干区凯旋路268号,浙江大学华家池校区中心大楼北楼440房间
个人简介
教育经历
2000/09-2003/06 协和医科大学 博士
研究经历
2014/12 - 浙江大学医学院/浙江大学儿童医院,教授
2013/06-2014/11 浙江大学生命科学学院,教授
2012/05-2013/06 美国Emory大学人类遗传学系,研究助理教授
2010/10- 2012/04 美国Emory大学人类遗传学系,Instructor
2008/12- 2010/09 美国Emory大学人类遗传学系,博士后
2006/12- 2008/11 美国新墨西哥州大学神经科学系,博士后
2004/05- 2006/11 美国Emory大学细胞生物学系,博士后
主要研究方向
1. 表观遗传学修饰对神经发生和成体神经干细胞功能的调控作用
2. 表观遗传学修饰在神经系统疾病中的作用
发表论文
47. Qiang Zhu, Xuejun Cheng, Yaxian Cheng, Junchen Chen, Huan Xu, Yuntao Gao, Xiaotao Duan, Junfeng Ji, Xuekun Li#, Wen Yi#. O-GlcNAcylation regulates the methionine cycle to promote pluripotency of stem cells. PNAS 2020 (doi/10.1073/ pnas.1915582117).
46. Yuhang Cao*,Yingliang Zhuang*, Junchen Chen, Weize Xu, Yikai Shou, Xiaoli Huang, Qiang Shu#, Xuekun Li#. Dynamic Effects of Fto in Regulating the Proliferation and Differentiation of Adult Neural Stem Cells of Mice. Hum Mol Genet 2019 (PMID: 31751468) (DOI: 10.1093/hmg/ddz274).
45. Yingliang Zhuang, Junchen Chen, Weize Xu, Qiang Shu, Xuekun Li#. The Detection of 5-Hydroxymethylcytosine in Neural Stem Cells and Brains of Mice. JoVE 2019,151,e59950.
44. Wang Y, Guo B, Xiao Z, Lin H, Zhang X, Song Y, Li Y, Gao X, Yu J, Shao Z, Li X, Luo Y, Li S. Long noncoding RNA CCDC144NL-AS1 knockdown induces naive-like state conversion of human pluripotent stem cells. Stem Cell Res Ther. 2019,10(1):220.
43. Junchen Chen*, Yi-Chang Zhang*, Chun-Min Huang*, Hui Shen, Bao-Fa Sun, Xuejun Cheng, Yujie Zhang, Yun-Gui Yang, Qiang Shu#, Ying Yang#, Xuekun Li#. mRNA Methyltransferase Mettl3 Regulates Neurogenesis and Neuronal Development via Modulating Histone Methyltransferase Ezh2. Genomics, Proteomics & Bioinformatics 2019,17(2):154-168.
42.Zhang X., Zhao X., Shu L., Li X#. Autism spectrum disorders: autistic phenotypes, complicated mechanisms. World J Pediatrics,2019. Doi: 10.1007/s12519-018-0210-2.
41.Ling Li, Yingliang Zhuang, Xingsen Zhao, Xuekun Li#. Long Noncoding RNA: Characterization and Biological Function in Development and Human Disease. Frontiers in Genetics 2019 (https://doi.org/10.3389/fgene.2018.00744).
40. Li Y, Park C, Jiang H, Li X, Vellón L. Noncoding RNAs and Base Modifications: Epigenomic Players Implicated in Neurological Disorders and Tumorigenesis. Int J Genomics,2018 Sep 24.
39. Li M, Zhang S, Zhao W, Hou C, Ma X, Li X, Huang B, Chen H, Chen D. RYBP modulates stability and function of Ring1B through targeting UBE3A. FASEB J 2018, 33(1):683-695.
38. Cheng Y, Li Z, Manupipatpong S, Lin L, Li X, Xu T, Jiang YH, Shu Q, Wu H, Jin P. 5-hydroxymethylcytosine alterations in the human postmortem brains of autism spectrum disorder. Hum Mol Genet 2018,27(17):2955-2964.
37. Tao H, Xie P, Cao Y, Shu L, Li L, Chen J, Tian G, Zhuang Y, Shu Q# Li X#. The Dynamic DNA Demethylation during Postnatal Neuronal Development and Neural Stem Cell Differentiation. Stem Cells Int 2018: 2186301.
36. Li X#, Yao B, Chen L, Kang Y, Li Y, Cheng Y, Li L, Lin L, Wang Z, Wang M, Pan F, Dai Q, Zhang W, Wu H, Shu Q, Qin Z, He C, Xu M, Jin P#. Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. Nature Communications 2017, 8:15903. (co-correspondence)
35. Li L, Zang L, Zhang F, Chen J, Shen H, Shu L, Liang F, Feng C, Chen D, Tao H, Xu T, Li Z, Kang Y, Wu H, Tang L, Zhang P, Jin P#, Shu Q#, Li X#. Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Hum Mol Genet 2017,26(13):2398-2411. (co-correspondence)
34. Liqi Shu, Wenjia Sun, Liping Li, Zihui Xu, Li Lin, Pei Xie, Hui Shen, Luoxiu Huang, Qi Xu, Peng Jin, Xuekun Li#. Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer’s disease. BMC Genomics2017,17(1):381-391.
33. Zhang P, Zhang L, Zhu L, Chen F, Zhou S, Tian T, Zhang Y, Jiang X, Li X, Zhang C, Xu L, Huang F. The change tendency of PI3K/Akt pathway after spinal cord injury. Am J Transl Res 2015,15;7(11):2223-3222.
32. Li, H., Zhong, X., Chau, KF., Santistevan, NJ., Guo,WX., Kong, GY., Li, X. , Kadakia, M., Masliah,J., Chi,JY., Jin, P., Zhang, J., Zhao, XY., Chang, Q. Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway. Nature communications 2014,5:5601-5610.
31. Sun, W*., Zang, L*., Shu, Q., Li., X#. From development to diseases: The role of 5hmC in brain. Genomics 2014,104:347-351.
30. Sun, W., Guan, M., and Li, X#. 5-hydroxymethylcytosine mediated DNA demethylation in stem cells and development. Stem cells and Dev 2014,23:923-930.
29. Xu, Z., Poidevin, M., Li, X., Li, Y., Shu, L., Nelson, DL., Li, H., Hales, CM., Gearing, M., Wingo, TS., Jin, P. Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc Natl Acad Sci USA 2013,110:7778-7783.
28. Wang. T., Wu, H., Li, Y., Szulwach, KE., Lin, L., Li, X., Chen, I., Goldlust, I., Chamberlain, S., Ananiev, G., Mowrey, J., Han, J., Kim, M., Yoon,Y., Rudd, M., Song, C., He, C., Chang, Q., Warren, S., Jin, P. Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency. Nature Cell biology 2013,15:700-711.
27. Hong,Y., Chan, CB., Kwon, IS., Li, X., Song, M., Lee, HP., Liu, X., Sompol, P., Jin, P., Lee, HG., Yu, SP., Ye, K. SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease. J Neurosci 2012,32:17262-12772.
26. Wang, T., Pan, Q., Lin L, Szulwach, KE., Song, CX., He, C., Wu, H., Warren, ST., Jin, P#., Duan, R#., Li, X#. Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human cerebellum. Hum Mol Genet 2012,21,5500-5510.
25. Yu, M., Hon, G., Szulwach, K., Song, C., Zhang, L., Kim, A., Li, X., Dai, Q., Park, B., Min, J., Jin, P., Ren, B., He, C. Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome. Cell 2012,149,1368-1380.
24. Xu,Z., Li, X#. DNA Methylation in Neurodegenerative Disorders. Curr Tran Geriatr Gerontol 2012,1:199–205.
23. Szulwach, K.E*., Li, X*., Li, Y., Song, C.X., Wu, H., Dai, Q., Irier, H., He, C. and Jin, P. 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging. Nature Neuroscience 2011,14:1607-1616 (* equal contribution).
22. Szulwach, KE., Li, X, Li, Y., Song, CX., Han, JW., Kim, S., Namburi,S., Hermetz, K., Kim, JJ., Rudd, MK., Yoon, YS., Ren, B., He, C., Jin, P. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet 2011, 7: e1002154.
21. Qurash,A., Li, X#., Jin, P#. (2011) Fragile X Mental Retardation Protein and Stem Cells. (* co-corresponding author; Robert B. Denman edited, Springer)
20. Song, C.X., Szulwach, K.E., Fu, Y., Dai, Q., Yi, C., Li, X., Li, Y., Chen, C.H., Zhang, W., Jian, X., Wang, J., Zhang, L., Looney, T.J., Zhang, B., Godley, L.A., Hicks, L.M., Lahn, B.T., Jin, P., and He, C. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nature Biotechnology 2011, 29,68-72.
19. Li, X. and Jin, P. Roles of small regulatory RNAs in determining neuronal identity. Nature Reviews Neurosci 2010,11:329-338.
18. Luo, Y., Shan, G., Guo, W., Smrt, R.D., Johnson, E., Li, X., Duan, R., Barkho, B.Z., Li, W., Jin, P., and Zhao, X. Fragile X mental retardation protein regulates adult neurogenesis. PLoS Genetics 2010,6: e1000898.
17. Smrt, RS., Szulwach, KE., Pfeiffer, RL., Li, X., Guo, W., Pathania, M., Luo, Y., Wilson, MC., Bordey, A., Jin, P., and Zhao, X. MicroRNA miR-137 modulates neuronal maturation through translational regulation of Mind Bomb-1. Stem Cells 2010,28:1060-1070.
16. Szulwach, KE*., Li, X*., Smrt, RS., Li, Y., Luo, Y., Lin, L., Santistevan, N., Li, W., Zhao X., and Jin, P. MeCP2-mediated crosstalk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biology 2010,189:127-141(*equal contribution).
15. Li, X., and Jin, P. (2009) Macro role(s) of microRNAs in fragile X syndrome? Neuromolecular Med 11:200-207.
14. Barkho, B., Munoz., A., Li, X., Li, L., Cunningham, L., and Zhao, X. Endogenous Matrix Metalloproteinase (MMP)-3 and MMP-9 mediate the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells 2008,26: 3139-3149.
13. Li, X., Tang, X., Jablonska, B., Aguirre, A., Gallo, V., and Luskin, M. p27KIP1 Regulates Neurogenesis in the Rostral Migratory Stream and Olfactory Bulb of the Postnatal Mouse. J Neurosci 2009,29:2902-2914.
12. Szulwach, K., Li, X., Zhao, X, Jin, P. (2009) Epigenetic Regulation of miRNA in Stem Cells. Current Perspective in miRNAs, (Springer).
11. Li, X., Barkho. BZ., Luo, Y., Smrt, RD., Santistevan, NJ., Liu, C., Kuwabara, T., Gage, FH., Zhao, X. Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. J Biol Chem 2008,283:27644-27652.
10. Allan, A., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K., Chen, D., Jin, P., Zhao, X. The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Hum Mol Genet 2008, 17:2047-2057.
9. Li, X., Zhao, X. Epigenetic Regulation of mammalian stem Cells. Stem Cells Dev 2008,17:1043-1052.
8. Li, X., Barkho, BZ., Zhao, X. (2008) Neural stem cells and neurogenic niche in the adult brain. Stem Cell Research and Therapeutics edited by Shi Y and Clegg D. Springer
7. Kong, X., Li, X., Cai, Z., Yang, N., Liu, Y., Shu, J., Pan, J., Zuo, P. Melatonin regulates viability and differentiation of rat midbrain neural stem cells. Cellular and Molecular Neurobiology 2008, 28:569-579.
6. Tang, X*., Falls, L*., Li, X., Lane, T., and Luskin, MB. Antigen-Retrieval Procedure for Bromodeoxyuridine Immunolabeling with Concurrent Labeling of Nuclear DNA and Antigens Damaged by HCl Pretreatment. J Neurosci 2007,27:5837-5844.
5. Cui, X., Zuo, P., Zhang, Q., Li, X., Hu, Y., Long, J., Packer, L., Liu, J. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: Protective effects of R-alpha-lipoic acid. J Neurosci Res 2006,83:1584-1590.
4. Zhang Q., Huang Y., Li, X., Cui X., Zuo P. and Li J. GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose. Neuroreport 2005, 16:1297-1301.
3. Zhang Q*., Li, X*., Cui X. and Zuo P. D-Galactose injured neurogenesis in the hippocampus of adult mice. Neurol Res 2005,27: 552-556.
2. Li, X., and Zuo P. Effects of Aβ25-35 on neurogenesis in the adult mouse subventricular zone and dentate gyrus. Neurol Res 2005,27: 218-222.
1.Li, X., Guo A. and Zuo P. Survival and differentiation of transplanted neural stem cell in the brain of MPTP-induced Parkinson’s disease model mouse. ACTA PHARMACOLOGICA SINICA 2003,24:1192-1198.