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徐俊博士论文索引

徐俊博士的研究方向和内容：

研究主要包括以下几个方面：

1.利用疾病特异的iPS细胞研究重大神经退行性疾病的机制。

这部分课题主要围绕两个关键科学问题进行：（1）如何将疾病特异性iPS细胞向相应疾病中的功能细胞定向诱导，并建立研究相关疾病的细胞或动物模型？（2）如何应用这样的疾病模型探索疾病发生的机制和规律，并发现对这些疾病有效治疗的新靶点和新途径？我们将首先建立严重危害人民健康的重大疾病的iPS细胞系，重点选择我们项目组有一定研究基础的疾病，并优先考虑具有遗传起因的家族病例，包括神经系统 （阿尔茨海默病AD、帕金森病PD和小儿脊髓性肌肉萎缩症SMA等)重大疾病。

2. 利用干细胞治疗脊髓损伤，中风，关节炎，糖尿病足的研究

建立脊髓损伤的动物模型，研究不同的干细胞，包括胚胎干细胞，诱导性多功能干细胞（iPS）神经前体干细胞（NPCs）、间充质干细胞（MSCs）和少突胶质前体干细胞（OPCs）对治疗脊髓损伤和中风的效果及作用机制, 并结合表达各种神经营养因子（BDNF, NT3,GDNF, et al）找到治疗脊髓损伤和中风的最佳策略。我们的课题组还建立了包括关节炎，糖尿病足，肝损伤等重大疾病的动物模型并开展了脂肪干细胞结合组织工程材料联合治疗的研究。

3.  研究神经突触形成的分子机制

神经元的信息传递是有神经突触介导，神经突触的形成对提高神经系统的功能例如神经系统的可塑性起着重要的作用。突触形成障碍被认为是引起一些发展性神经病的病因，如Fragile Mental Retardation(FMR) 和Rett综合症(Rett syndrome)。研究突触形成的分子机制是神经科学中的重大基础问题，对理解很多重大神经系统疾病的致病机制有深远的影响。我们将具体围绕着星形胶质细胞在神经突触形成中的作用开展研究工作。

4. 神经干细胞在衰老过程中的DNA损伤修复及应答反应的调控机制的研究

本课题的主要目标是研究在衰老过程中DNA损伤修复及其应答反应对神经干细胞功能的影响，从而揭示神经干细胞衰老的分子调控机制。 具体目标包括：

1）确定在衰老过程中，神经干细胞是否对神经系统的衰老起到重要作用？

2）发现在衰老状态下，神经干细胞的细胞病理学特征，及其增殖和分化特性的改变。

3）研究衰老过程中，神经干细胞的DNA损伤及修复能力的变化及其与神经干细胞功能衰退的相关性。

4）利用特异的DSB修复的荧光报道系统，深入研究DBS相关的两个重要修复途径HR（homologous recombination）和NHEJ(non-homologous end-jointing)在神经干细胞的DNA损伤修复中的作用及其在衰老的模型中的变化及调控机制。

5）利用分子遗传学和转基因小鼠，研究与衰老相关的重要基因如Sirt1, ATM, Ku80及P53在衰老过程中对DNA损伤修复的调节机制

徐俊博士已经发表的论文 ：

57. Zhao, S., Liu, Y., Wang, J., Wen, Y., Wu, B., Yang, D., Wang, G., Xiu, G., Ling, B., Du, D., & Xu, J. (2023). ADSCs increase the autophagy of chondrocytes through decreasing miR-7-5p in Osteoarthritis rats by targeting ATG4A. International immunopharmacology, 120, 110390. https://doi.org/10.1016/j.intimp.2023.110390

4056. Le W, Zhou F, Xiang J, et al. Preliminary Study on 53BP1-Mediated DNA Double-Strand Break Response in Spermatogonial Stem Cells. Reprod Sci. 2023;30(5):1572-1584. doi:10.1007/s43032-022-01122-7

55. Jiang T, Xu C, Gao S, Zhang J, Zheng J, Wu X, Lu Q, Cao L, Yang D, Xu J, Chen X. Cathepsin L-containing exosomes from α-synuclein-activated microglia induce neurotoxicity through the P2X7 receptor. NPJ Parkinsons Dis. 2022 Oct 6;8(1):127. doi: 10.1038/s41531-022-00394-9.

54. Wu B, Feng J, Guo J, Wang J, Xiu G, Xu J, Ning K, Ling B, Fu Q, Xu J. ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis. Stem Cell Res Ther. 2022 Oct 4;13(1):494. doi: 10.1186/s13287-022-03049-x.

53. Qi L, Wang J, Chen X, Ding Y, Ling B, Wang W, Xu J, Xue Z. Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis. Heliyon. 2022 Oct 18;8(11):e11148.

52. Tian X, Zhu Z, Wang G, Xu J, Liang A, Zhang W. Inhibition of DEK Enhances Doxorubicin-Induced Apoptosis and Cell Cycle Arrest in T-Cell Acute Lymphoblastic Leukemia Cells. Dis Markers. 2022 Jun 20;2022:9312971.

51.Jian Wang # , Rui Hao # , Tianfang Jiang # , Xuanxuan Guo, Fei Zhou , Limei Cao , Fengjuan Gao , Guangming Wang , Juan Wang , Ke Ning , Chunlong Zhong* , Xu Chen* , Ying Huang* , Jun Xu* , Shane Gao*. Rebuilding Hippocampus Neural Circuit with hADSC-derived Neuron Cells for Treating Ischemic Stroke

 Cell & Bio  2022 Apr 4;12(1):40  (*Corresponding author)

50. Chuanming Dong#, Xianli Wang#, Lixin Sun#, Liang Zhu, Danjing Yang, Shane

Gao, Wenjun Zhang, Bin Ling, Aibin Liang*, Zhengliang Gao*, Jun Xu*. ATM modulates subventricular zone neural stem cell maintenance and senescence

through Notch signaling pathway. Stem Cell Res  2022 Jan;58:102618 (Corresponding author)

49. Ren J#, Wang X#, Dong C#, Wang G#, Zhang W, Cai C, Qian M, Yang D, Ling B, Ning K, Mao Z, Liu B, Wang T, Xiong L, Wang W*, Liang A*, Gao Z*, Xu J*. Sirt1 Protects Subventricular Zone-Derived Neural Stem Cells from DNA Double-Strand Breaks and Contributes to Olfactory Function Maintenance in Aging Mice. Stem Cells. 2022 May 27;40(5):493-507.   (*Corresponding author)

48.Fangce Wang#，Zheng Li#，Jie Zhou, Guangming Wang,Wenjun zhang*，Jun Xu *Aibin Liang* .SIRT1 regulates the phosphorylation and degradation of P27 by deacetylating CDK2 to promote T-cell acute lymphoblastic leukemia progression. J. Exp. Clin. Cancer Res 2021 Aug 18;40(1):259 (*Corresponding author)

47.Zheng Li#，Fangce Wang#, Xiaoxue Tian, Jun Long, Bin Ling, Wenjun zhang*，Jun Xu *Aibin Liang*. HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML. J. Exp. Clin. Cancer Res 2021 Jun 24;40(1):210 (*Corresponding author)

46.Min-Min Lou#, Xiao-Qiang Tang#,Guang-Ming Wang#, Jia He,Fang Luo,Ming-Feng Guan,Fei Wang,Huan Zou,Jun-Ying Wang,Qun Zhang,Ming-Jian Xu,Qi-Li Shi,Li-Bing Shen,Guo-Ming Ma,Yi Wu,Yao-Yang Zhang,Ai-bin Liang,Ting-Hua Wang,Liu-Lin Xiong,Jian Wang*,Jun Xu* ,Wen-Yuan Wang* Long noncoding RNA BS-DRL1 modulates DNA damage response and genome stability in the central nervous systemby interacting with HMGB1.Nat Commun 2021 Jul 1;12(1):4075 (*Corresponding author)

45. Chiqi Chen#, Xiaoxin Hao#, Xiaoyun Lai#, Hongfang Shao#, Jun Zhu#, Dan

Huang, Hao Gu, Tinghua Zhang, Zhuo Yu, Li Xie, Ligen Liu, Xiaocui Zhang, Yi

Yang, Jun Xu*, Yuzheng Zhao*, Zhigang Lu*, Junke Zheng*. Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B-cell acute lymphoblastic leukemia. Science Advance 2021 Mar 10;7(11):eabd6280 (accepted) (*Corresponding author)

44. Qiande Hu*, Liang Zhu, Yuan Lia, Jianjun Zhou* , Jun Xu* . bACTA1 is inhibited by PAX3-FOXO1 through RhoA-MKL1-SRF signaling pathway and impairs cell proliferation, migration and tumor growth in Alveolar Rhabdomyosarcoma Cell & Bio 2021 Jan 28;11(1):25  (*Corresponding author)

43. Jian Wang, Xuanxuan Guo, Zhanrong Kang, Lingbin Qi, Ying Yang, Juan Wang, Jun Xu, and Shane Gao. Roles of Exosomes from Mesenchymal Stem Cells in Treating Osteoarthritis. Cell Reprogram  2020 Jun;22(3):107-117

42. Zhuoyi Fan, Huacheng Luo, Jie Zhou , Fangce Wang , Wenjun Zhang, Jian Wang , Shuo Li , Qian Lai , Yueshuang Xu , Guangming Wang , Aibin Liang*, Jun Xu*. Checkpoint kinase‑1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair Oncol Rep . 2020 Nov;44(5):2152-2164  (*Corresponding author)

41. Lian Wang , Shengkai Jin , Peibin Dai , Tianran Zhang, Yanghua Shi , Guihai Ai , Xiaowen Shao , Yutong Xie , Jun Xu*, Zhongping Chen*, Zhengliang Gao* . p57 Kip2 is a master regulator of human adipose derived stem cell quiescence and senescence . Stem Cell Res 2020 Apr; 44:101759  (*Corresponding author)

40. Ma R, Wang M, Gao S, Zhu L, Yu L, Hu D, Zhu L, Huang W, Zhang W, Deng J, Pan J, He H, Gao Z, Xu J*, Han X*. miR-29a Promotes the Neurite Outgrowth of Rat Neural Stem Cells by Targeting Extracellular Matrix to Repair Brain Injury. Stem Cells Dev 2020 May 1;29(9):599-614  (*Corresponding author)

39. Wang F, Li Z, Wang G, Tian X, Zhou J, Yu W, Fan Z, Dong L, Lu J, Xu J, Zhang W*, Liang A*. Integrated transcriptomic and epigenetic data analysis identifies aberrant expression of genes in acute myeloid leukemia with MLL‑AF9 translocation. Mol Med Rep. 2020  21(2):883-893

38. Zhou X, Ning K, Ling B, Chen X, Cheng H, Lu B, Gao Z, Xu J*. Multiple Injections of Autologous Adipose-Derived Stem Cells Accelerate the Burn Wound Healing Process and Promote Blood Vessel Regeneration in a Rat Model. Stem Cells Dev. 2019 28(21):1463-1472  (*Corresponding author)

37. Gao SE, Guo XX, Zhao SM, Jin YP, Zhou F, Yuan P, Cao LM, Wang J, Qiu Y, Sun CX, Kang ZR, Gao FJ, Wei W,  Hu X, Yang DJ, Qin Y, Ning K, Shaw PJ, Zhong GS*, Cheng LM*, Zhu HW*, Gao ZL*, Chen X*, Xu J*, Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury, Cell Death Dis, 2019 Aug 8;10(8):597(*Corresponding author)

36. Sun C, Zhu L, Ma R, Ren J, Wang J, Gao S, Yang D, Ning K, Ling B*, Lu B*, Chen X*, Xu J*. Astrocytic miR-324-5p is essential for synaptic formation by suppressing the secretion of CCL5 from astrocytes. Cell Death Dis. 2019 Feb 13;10(2):141.

35. Zhu L, Sun C, Ren J, Wang G, Ma R, Sun L, Yang D, Gao S, Ning K, Wang Z, Chen X, Chen S*, Zhu H*, Gao Z*, Xu J*. Stress-induced precocious aging in PD-patient iPSC-derived NSCs may underlie the pathophysiology of Parkinson’s disease. Cell Death Dis. 2019 Feb 4;10(2):105. (*Corresponding author)

34. Wenlei Yu, Liang Li, Guangming Wang, Wenjun Zhang*, Jun Xu*, Aibin Liang*, KU70 Inhibition Impairs Both Non-Homologous End Joining and Homologous Recombination DNA Damage Repair Through SHP-1 Induced Dephosphorylation of SIRT1 in Adult T-Cell Leukemia-Lymphoma Cells, Cell Physiol Biochem 2018;49(6):2111-2123. (*Corresponding author)

33. Yinpeng Jin, Junyi Wang, Hongchao Li, Shane Gao, Rongfeng Shi, Danjing Yang, Xianli Wang, Xi Wang, Liang Zhu, Xiaojin Wang, Chengwei Chen, Ke Ning, Zhengliang Gao*, Jun Xu*, Qingchun Fu*, Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19, EBioMedicine,Volume 34,2018,Pages 231-242 (*Corresponding author)

32. W Le, L Qi L, C Xu, Z Xiang, Z Mao, J Zhang*, J Xu* and D Wu*. Preliminary study of the homologous recombination repair pathway in mouse spermatogonial stem cells[J]. Andrology, 2018, 9 (*Corresponding author)

31. Guangming Wang, Fangce Wang, Jie Ren, Yue Qiu, Wenjun Zhang, Shane Gao, Danjing Yang, Zhigang Wang, Aibin Liang*, Zhengliang Gao*, Jun Xu*, SIRT1 Involved in the Regulation of Alternative Splicing Affects the DNA Damage Response in Neural Stem Cells. Cell Physiol Biochem 2018;47:657-669 (*Corresponding author)

30. Qian M, Liu Z, Peng L, Tang X, Meng F, Ao Y, Zhou M, Wang M, Cao X, Qin B, Wang Z, Zhou Z, Wang G, Gao Z, Xu J, Liu B* (2018) Boosting ATM activity alleviates ageing and extends lifespan in a mouse model of progeria. Elife  May 2;7:e34836

29. Liang Q, Cai C, Duan D, Hu X, Hua W, Jiang P, Zhang L, Xu J*, Gao Z* (2018) Postnatal Vitamin D Intake Modulates Hippocampal Learning and Memory in Adult Mice. Frontiers in Neuroscience 12:141 (*Corresponding author)

28. Kang S, Zhang Z, Liu X, Manfredsson F, Benskey M, Cao X, Luo H, Xu J*, Sun Y, K Ye*. (2017) TrkB neurotrophic activities are blocked by α-synuclein, triggering dopaminergic cell death in Parkinson’s disease. PNAS 114(40):10773-10778 (*Corresponding author)

27. Wang J, Li J, Yang J, Zhang L, Gao S, Jiao F, Yi M, Xu J*. （2017）MicroRNA‑138‑5p regulates neural stem cell proliferation and differentiation in vitro by targeting TRIP6 expression. Mol Med Rep 16(5):7261-7266 (*Corresponding author)

26. Ciervo Y, Ning K, Xu J, Shaw PJ, Mead RJ*. (2017) Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis. Mol Neurodegener 12(1):85 (*Corresponding author)

25. Wang X║, Sun C║, Zhu L, Sun L, Ma R, Wang Z, Lu B*, Chen X*, Xu J*. (2017) Quantitative proteomic analysis revealed changes in protein synthesis and mitochondrial functions after acute DNA damage in mouse neural stem cells. Neurosci Lett. 653:355-361 (*Corresponding author,║equal contribution)

24. Shi R║, Jin Y║, Cao C, Han S, Shao X, Meng L, Cheng J, Zhang M, Zheng J, Xu J*, Li M*. （2016） Localization of human adipose-derived stem cells and their effect in repair of diabetic foot ulcers in rats Stem Cell Res Ther. 7(1):155 (*Corresponding author,║equal contribution )

23. Wang X║, Dong C║, Sun L║, Zhu L, Sun C, Ma R, Ning K, Lu B*, Zhang J*, Xu J*. (2016) Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease.  Sci Rep.6:37443. doi: 10.1038/srep37443. (*Corresponding author,║equal contribution )

22. Gao SE*║, Wang Juan║, Wu ZY, Yuan P, Gao FJ, Zhou F, Cao LM, Chen X, Zhu HW and Xu J* (2015) Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? Autism Open Access, 5(3):151, 2015. (*Corresponding author,║equal contribution )

21. Zhang WJ║, Wu HX║, Yang M║, Ye SG, Li L, Zhang H, Hu J, Wang XG*,  Xu J*, Liang AB* (2015) SIRT1 inhibition impairs non-homologous end joining DNA damage repair by increasing Ku70 acetylation in chronic myeloid leukemia cells. Oncotarget   3. doi: 10.18632/oncotarget.6455. [Epub ahead of print] (*Corresponding author,║equal contribution )

20. Zhu L║, Dong CM║, Ma RJ, Sun CX, Zhu HW*, Xu J* (2015) Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy.  BBRC 464(2):526-33 (*Corresponding author,║equal contribution )

19. Yang DJ║, Zhu L║, Ren J, Ma RJ, Zhu HW*, Xu J* (2015) Dysfunction of autophagy as the pathological mechanism of motor neuron disease based on a patient-specific disease model. Neuroscience Bulletin 31(4):445-51 (*Corresponding author,║equal contribution )

18. Zhou F║, Gao S║, Wang L║, Sun CX, Chen L, Li Q, Yuan P, Zhao H, Yi Y, Qin Y, Dong ZY,  Cao LM, Ren HY, Zhu L, Ma RJ, Lu B, Liang AB, Xu GT, Zhu HW, Gao ZL, Ma J*, Xu J*, Chen X*  (2015). Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model. Stem cell research & therapy 6, 92.

(*Corresponding author,║equal contribution )

17. Dong CM║, Wang XL║, Wang GM║, Zhu L, Ma RJ, Sun CX, Deng HT, Liang A*, Gao ZL*, Xu J* (2014) A stress-induced cellular aging model with postnatal neural stem cells. Cell death & disease 5:e1116 (*Corresponding author,║equal contribution )

16. Yang DJ║, Wang XL║, Ismail A, Ashman CJ, Valori CF, Wang G, Gao S, Higginbottom A, Ince PG, Azzouz M, Xu J*, Shaw PJ*, Ning K* (2014) PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons. Cell death & disease 5:e1096. (*Corresponding author,║equal contribution )

15. Gao S║, Zhao P║, Lin C, Sun Y, Wang Y, Zhou Z, Yang D, Wang X, Xu H, Zhou F, Cao L, Zhou W, Ning K, Chen X*, Xu J* (2014) Differentiation of Human-Adipose Derived Stem Cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds. Tissue engineering Part A 20(7-8):1271-84 (*Corresponding author,║equal contribution )

14. Shi S║, Gao S║, Cao T, Liu J, Gao X, Hao J, Lv C, Huang H, Xu J*, Yao T* (2013) Targeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+). PloS one 8:e84419. (*Corresponding author,║equal contribution )

13. Peng H, Kang N, Xu J*, Stanton PK, Kang J* (2013) Two distinct modes of exocytotic fusion pore expansion in large astrocytic vesicles. The Journal of biological chemistry 288:16872-16881. (*Corresponding author )

12. Hu G, Huang K, Yu J, Gopalakrishna-Pillai S, Kong J, Xu H, Liu Z, Zhang K, Xu J, Luo Y, Li S, Sun YE, Iverson LE, Xue Z, Fan G (2012) Identification of miRNA signatures during the differentiation of hESCs into retinal pigment epithelial cells. PloS one 7:e37224.

11. Gustavsson N, Wang X, Wang Y, Seah T, Xu J, Radda GK, Sudhof TC, Han W (2010) Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion. PloS one 5:e15414.

10. Shin OH║, Xu J║, Rizo J, Sudhof TC (2009) Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release. Proceedings of the National Academy of Sciences of the United States of America 106:16469-16474. (║equal contribution)

9. Xu J, Pang ZP, Shin OH, Sudhof TC (2009) Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nature neuroscience 12:759-766

8. Xu J, Mashimo T, Sudhof TC (2007a) Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron 54:567-581.

7. Xu J, Peng H, Kang N, Zhao Z, Lin JH, Stanton PK, Kang J (2007b) Glutamate-induced exocytosis of glutamate from astrocytes. The Journal of biological chemistry 282:24185-24197.

6. Wu H, Xu J║, Pang ZP║, Ge W║, Kim KJ, Blanchi B, Chen C, Sudhof TC, Sun YE (2007) Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proceedings of the National Academy of Sciences of the United States of America 104:13821-13826. (║equal contribution)

5. Kang N║, Xu J║, Xu Q, Nedergaard M, Kang J (2005) Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. Journal of neurophysiology 94:4121-4130. (║equal contribution)

4. Xu J, Kang N, Jiang L, Nedergaard M, Kang J (2005) Activity-dependent long-term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 25:1750-1760.

3. Xu J, Kang J (2005) The mechanisms and functions of activity-dependent long-term potentiation of intrinsic excitability. Reviews in the neurosciences 16:311-323.

2. Kang N, Jiang L, He W, Xu J, Nedergaard M, Kang J (2004) Presynaptic inactivation of action potentials and postsynaptic inhibition of GABAA currents contribute to KA-induced disinhibition in CA1 pyramidal neurons. Journal of neurophysiology 92:873-882.

1. Jiang L, Xu J, Nedergaard M, Kang J (2001) A kainate receptor increases the efficacy of GABAergic synapses. Neuron 30:503-513.