博士生导师李学坤教授实验室简介

编辑:admin 时间:2015年08月25日 访问次数:2765

导师个人介绍

李学坤,教授,博士生导师,浙江省“千人计划”入选者,于2003年获得中国协和医科大学药理学博士学位。先后在美国新墨西哥州大学和Emory大学进行博士后研究,并晋升为研究助理教授。以第一作者、通讯作者和共同作者在Nature NeuroscienceJournal of Cell Biol JBC Journal of NeuroscienceNature Reviews NeurosciencePLoS GeneticsNature BiotechCell等国际学术期刊发表论文30多篇,并获得美国Fragile X syndrome foundationAutism speaks foundation的博士后研究基金和独立研究基金资助。2013年加盟浙江大学,研究得到科技部“973”计划、国家自然基金委和人社部回国人员基金(优秀类)等资助。

 

研究介绍

“一方水土养一方人”,不同的地域和饮食习惯对应和丰富着人的性格,所以又有了“江南多才子,塞北出侠士”的说法。环境和饮食是如何与人相互影响的?过去几十年的研究表明,表观遗传学机制是人与环境对话的重要桥梁。表观遗传学不仅在胚胎和出生后发育、细胞功能等多种生物学过程中发挥重要作用,而且在人类疾病的发生和发展中扮演了重要角色。研究表观遗传学,对于认识生命的奥妙和疾病的治疗具有重要意义。神经干细胞是一类具有自我更新能力和多分化潜能的干细胞。成体神经干细胞产生的神经元可以整合到神经回路中,发挥生理功能,参与学习和记忆过程,并与多种疾病相关。

我们实验室采用细胞和分子生物学、表观遗传学和生物信息学等手段,依托浙江大学儿童医院,充分利用丰富的临床病例资源,致力于探索表观遗传学机制特别是DNARNA修饰在神经干细胞调控、神经和心脏发育以及疾病中的作用,从而为相关疾病的治疗提供新的思路和靶点。

实验室重点研究方向:

1.DNARNA修饰在成体神经干细胞和神经系统疾病中的调控作用;

2. DNARNA修饰在心脏发育和先天性心脏病中的调控作用;

3. DNA去甲基化与内耳发育。

 

研究论文

1.     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 8: 15903(2017). (# co-correspondence).
 
2.     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 26(13): 2398-2411(2017). (# co-correspondence).
 
3.     Li Y, Park C, Vellón L, Li X. iPSCs: From Bench to Clinical Bed. Stem Cells Int. 8367587(2016).
 
4.     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 Genomics 17(1):381-391(2016).
 
5.     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 15;7(11):2223-3222(2015).
 
6.     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 5:5601-5610 (2014)
 
7.     Sun, W*., Zang, L*., Shu, Q., Li., X. From development to diseases: The role of 5hmC in brain. Genomics104:347-351 (2014).
 
8.     Sun, W., Guan, M., and Li, X. 5-hydroxymethylcytosine mediated DNA demethylation in stem cells and development. Stem cells and Dev 23:923-930 (2014).
 
9.     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 110:7778-7783 (2013).
 
10. 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 15:700-711(2013).
 
11. Hong,Y., Chan, CB., Kwon, IS., Li, X., Song, M., Lee, HP., Liu, X., Sompol, P.,  Jin, P., Lee, HG., Yu, SP., Ye, K. (2012) SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease. J Neurosci 32:17262-12772.
 
12. Wang, T., Pan, Q., Lin L, Szulwach, KE., Song, CX., He, C., Wu, H., Warren, ST., Jin, P., Duan, R., Li, X. (2012) Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human cerebellum, Hum Mol Genet21,5500-5510.
 
13. 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. (2012) Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome. Cell149,1368-1380.
 
14. Xu,Z., Li, X. DNA Methylation in Neurodegenerative Disorders. Curr Tran Geriatr Gerontol1:199–205 (2012).
 
15. Szulwach, K.E*., Li, X*., Li, Y., Song, C.X., Wu, H., Dai, Q., Irier, H., He, C. and Jin, P. (2011) 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging. Nature Neuroscience 14:1607-1616 (* equal contribution).
 
16. 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. (2011) Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet 7: e1002154.
 
17. Qurash,A., Li, X*., Jin, P*. (2011) Fragile X Mental Retardation Protein and Stem Cells. (* co-corresponding author; Robert B. Denman edited, Springer)
 
18. 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. (2011) Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nature Biotechnology 29,68-72.
 
19. Li, X. and Jin, P. (2010) Roles of small regulatory RNAs in determining neuronal identity. Nature Reviews Neurosci 11:329-338.
 
20. 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. (2010) Fragile X mental retardation protein regulates adult neurogenesis. PLoS Genetics 6: e1000898.
 
21. Smrt, RS., Szulwach, KE., Pfeiffer, RL., Li, X., Guo, W., Pathania, M., Luo, Y., Wilson, MC., Bordey, A., Jin, P., and Zhao, X.(2010)MicroRNA miR-137 modulates neuronal maturation through translational regulation of Mind Bomb-1. Stem Cells 28:1060-1070.
 
22. Szulwach, KE*., Li, X*., Smrt, RS., Li, Y., Luo, Y., Lin, L., Santistevan, N., Li, W., Zhao X., and Jin, P. (2010) MeCP2-mediated crosstalk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biology 189:127-141(*equal contribution).
 
23. Li, X., and Jin, P.(2009) Macro role(s) of microRNAs in fragile X syndrome? Neuromolecular Med11:200-207.
 
24. Barkho, B., Munoz., A., Li, X., Li, L., Cunningham, L., and Zhao, X. (2008) Endogenous Matrix Metalloproteinase (MMP)-3 and MMP-9 mediate the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells 26: 3139-3149.
 
25. Li, X., Tang, X., Jablonska, B., Aguirre, A., Gallo, V., and Luskin, M. (2009) p27KIP1 Regulates Neurogenesis in the Rostral Migratory Stream and Olfactory Bulb of the Postnatal Mouse. J Neurosci 29:2902-2914.
 
26. Szulwach, K., Li, X., Zhao, X, Jin, P. (2009) Epigenetic Regulation of miRNA in Stem Cells. Current Perspective in miRNAs, (Springer).
 
27. Li, X., Barkho. BZ., Luo, Y., Smrt, RD., Santistevan, NJ., Liu, C., Kuwabara, T., Gage, FH., Zhao, X. (2008) Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. J Biol Chem 283:27644-27652.
 
28. Allan, A., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K., Chen, D., Jin, P., Zhao, X. (2008) The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Hum Mol Genet 17:2047-2057.
 
29. Li, X., Zhao, X. (2008) Epigenetic Regulation of mammalian stem Cells. Stem Cells Dev 17:1043-1052.
 
30. 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   
 
31. Kong, X., Li, X., Cai, Z., Yang, N., Liu, Y., Shu, J., Pan, J., Zuo, P. (2008) Melatonin regulates viability and differentiation of rat midbrain neural stem cells. Cellular and Molecular Neurobiology 28:569-579.
 
32. Tang, X*., Falls, L*., Li, X., Lane, T., and Luskin, MB. (2007) Antigen-Retrieval Procedure for Bromodeoxyuridine Immunolabeling with Concurrent Labeling of Nuclear DNA and Antigens Damaged by HCl Pretreatment. J Neurosci 27:5837-5844.
 
33. Cui, X., Zuo, P., Zhang, Q., Li, X., Hu, Y., Long, J., Packer, L., Liu, J. (2006) Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: Protective effects of R-alpha-lipoic acid. J Neurosci Res83:1584-1590.
 
34. Zhang Q., Huang Y., Li, X., Cui X., Zuo P. and Li J. (2005) GM1 ganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose. Neuroreport 16:1297-1301.
 
35. Zhang Q*., Li, X*., Cui X. and Zuo P. (2005) D-Galactose injured neurogenesis in the hippocampus of adult mice. Neurol Res 27: 552-556.
 
36. Li, X., and Zuo P. (2005) Effects of Aβ25-35 on neurogenesis in the adult mouse subventricular zone and dentate gyrus. Neurol Res 27: 218-222.
 
37. Li, X., Guo A. and Zuo P. (2003) Survival and differentiation of transplanted neural stem cell in the brain of MPTP-induced Parkinson’s disease model mouse. ACTA PHARMACOLOGICA