李家驿
职称：教授
联系电话：
E-mail: lijiayi@cmu.edu.cn, wl1042@gmail.com
研究方向：神经退行性疾病发病机理及早期干预；干细胞生物学及其应用
李家驿 教授，博士生导师
分别于1982年和1988年在西南医科大学（原 泸州医学院）及四川大学（原 华西医科大学）获得学士和硕士学位，1995年在瑞典哥德堡大学获得博士学位。 1999年任瑞典哥德堡大学副教授。2001年任瑞典隆德大学副教授，2011年任隆德大学终身教授。2013-2018年曾任东北大学生命科学与健康学院院长。主持及参与国家国家自然科学基金重点项目、联合项目等科研项目。
科研方向
（一） 神经退行性疾病，如帕金森病和亨廷顿病的病原性机理研究
发现帕金森病病致病蛋白细胞间“感染”新机制，明确了α-突触核蛋白从一个“患病的”细胞转运到另一个正常细胞并被远程转运是帕金森病发病过程中的一个重要机制，此“朊蛋白样(prion-like)传染”机制对于帕金森病全脑的神经病理学现象的形成起到了重要的作用。目前，我们以此为基点，致力于进一步探索帕金森病的致病过程，寻找可能影响及干预帕金森病病变聚集和传播的全新的治疗策略。
（二） 神经退行性疾病中突触功能及轴浆运输功能障碍的研究
我们提出关于帕金森病与亨廷顿病发病机制的新假说，其相关病理蛋白造成轴浆运输及突触功能异常，由此导致神经细胞环路的“功能联系阻断”，最终引起神经细胞死亡。此假说为研究神经退行性疾病发病进程中早期病理改变提供了新的研究方向。
（三） 神经生成（Neurogenesis）改变及神经移植及干细胞疗法在神经退行性疾病中的应用研究
研究神经退行性疾病如何影响内源性神经干细胞的增值及分化，同时，研究在神经移植包括干细胞疗法中，移植细胞与宿主细胞的相互关系、环路重建及功能整合，为干细胞疗法在神经退行性疾病中的应用提供实验依据。
主要学术贡献
1. “α-synuclein”在细胞间传播
我们对PD患者移植11-16年胎儿中脑多巴胺能神经元进行追踪分析，结果显示，移植的中脑多巴胺能神经元形态良好（A），在部分移植的多巴胺能神经元中发现明显的PD病理性蛋白—α-synuclein的沉积（B）。我们发现分别移植12年及16年的PD患者中约40%及80%的TH阳性神经元出现大量α-synuclein的沉积。结果表明移植中脑多巴胺能神经元十年PD患者，大多数中脑多巴胺能神经元在功能上均未受损，而接受移植的PD患者能够得到症状缓解。该研究的重大发现为PD发病机制的研究提供重要思路。
2. 检测不同年龄的BAC-α-syn-GFP小鼠结肠传入神经元磷酸化α-syn
通过对过表达a-syn的转基因小鼠肠道的观察，我们发现随着年龄增加（6月、9月及24月龄），BAC-α-syn-GFP鼠肠蠕动速度变慢，结肠中a-syn的含量及其磷酸化程度随着年龄的增加逐渐增加，反映了PD病理的肠道起源。
3. 诱导型多能干细胞的多巴胺能分化
上图显示诱导型多能干细胞克隆（A、B）多巴胺能分化12天（C、D、E）和分化25天（F）的形态。
代表性论文
1. Xue-Jing Wang, Ming-Ming Ma, Le-Bo Zhou, Xiao-Yi Jiang, Miao-Miao Hao, Robert K.F. Teng, Erxi Wu, Bei-Sha Tang*, Jia-Yi Li*, Jun-Fang Teng*, Xue-Bing Ding* (2020) Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy. Nature Communication 11:934.
2. Yan Sun, Chuang Guo, Lin Yuan, Wen Li, Wang Zhan-You, Feng Yue Y*, Jia-Yi Li* (2020) Diabetes Mellitus induces prodromal pathological alterations of Parkinson’s Disease in spontaneously-developed T2DM Cynomolgus Monkeys. Frontiers in Neuroscience 14: Article 63.
3. Caroline Haikal, Qian-Qian Chen, Jia-Yi Li* (2020) Microbiome changes: an indicator of Parkinson’s Disease? Translational Neurodegeneration 8:38.
4. Qian-Qian Chen, Caroline Haikal, Wen Li and Jia-Yi Li*. Gut inflammation in association with pathogenesis of Parkinson’s disease. Frontiers in Molecular Neuroscience 12:218.
5. Lin Yuan, Jia-Yi Li* (2019) Exosomes in Parkinson’s disease: Current perspectives and future challenges. ASC Chemical Neuroscience 10: 963-972.
6. Jia-Zhen Wu, Mustafa Ardah, Caroline Haikal, Alexander Svanbergsson, Meike Diepenbroek, Nishant N. Vaikath, Wen Li, Zhan-You Wang, Tiago F. Outeiro, Omar M. El-Agnaf, Jia-Yi Li* (2019) Dihydromyricetin and Salvianolic acid B reduce alpha-synuclein aggregation by enhancing chaperone-mediated autophagy. Translational Neurodegeneration 8:18.
7. Qian-Qian Chen, Caroline Haikal, Wen Li, Ming-Tao Li, Zhan-You Wang, Jia-Yi Li* (2018) Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson's disease. Translational Neurodegeneration 7:13.
8. Chong-Bin Zhong, Qian-Qian Chen, Caroline Haikal, Wen Li, Alexander Svanbergsson, Meike Diepenbroek, Jia-Yi Li* (2017) Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson’s Disease. Neuroscience Bulletin 33(5): 483–492.
9. Wen Li, Elisabet Englund, Håkan Widner, Bengt Mattsson, Danielle van Westen, Jimmy Lätt,e Stig Rehncrona, Patrik Brundin, Anders Björklund, Olle Lindvall, Jia-Yi Li* (2016) Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating Parkinsonian brain. Proceedings of the National Academy Of Sciences of the united states of America 113: 6544-6549.
10. Wen Li, Shengdi Chen *, Jia-Yi Li* (2015) Human induced pluripotent stem cells in Parkinson’s disease: a novel cell source of cell therapy and disease modeling. Progress in Neurobiology 134:161-177.
11. Reena Prity Murmu, Wen Li, Zsuzsanna Szepesi, Jia-Yi Li* (2015) Altered sensory experience exacerbates stable dendritic spine and synapse loss in a mouse model of Huntington’s disease. Journal of Neuroscience 35:287-298.
12. Laurent Roybon*, Teresa L. Mastracci, Joyce Li, Simon R. W. Stott, Andrew B. Leiter, Lori Sussel, Patrik Brundin, Jia-Yi Li* (2015) The origin, development and molecular diversity of rodent olfactory bulb glutamatergic neurons distinguished by expression of transcription factor NeuroD1. Plos One 1-21.
13. Staffan Holmqvist , Oldriska Chutna, Luc Bousset, Patrick Aldrin-Kirk, Wen Li, Tomas Björklund, Zhan-You Wang, Laurent Roybon, Ronald Melki, Jia-Yi Li* (2014) Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathologica. 128: 805-820.
14. Reena Prity Murmu , Wen Li, Anthony Holtmaat, Jia-Yi Li *(2013) Dendritic spine instability leads to progressive neocortical spine loss in a mouse model of Huntington’s disease. Journal of Neuroscience 33: 12997-13009
15.ChristianHansen*, TomasBjörklund, GeraldineH.Petitc, MartinLundblad, Reena PrityMurmua, PatrikBrundince, Jia-Yi Li* (2013) A novel alpha-synuclein GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of alpha-synuclein GFP. Neurobiology of Disease 56: 145-155.
16. Jia-Yi Li,Laura Conforti* (2013) Axonopathies in Huntington’s disease. Experimental Neurology 246: 62-71
17. Iksoo Jeon , Nayeon Lee, Jia-Yi Li, In-Hyun Park, Kyoung Sun Park, Jisook Moon, Sung Han Shim, Chunggab Choi, Da-Jeong Chang, Jihye Kwon, Seung-Hun Oh, Dong Ah Shin, Hyun Sook Kim, Jeong Tae Do, Dong Ryul Lee, Manho Kim, Kyung-Sun Kang, George Q Daley, Patrik Brundin*, Jihwan Song* (2012) Neuronal properties, in vivo effects and pathology of a Huntington’s disease patient-derived induced pluripotent stem cells. Stem cells 30: 2054-2062
18. Christian Hansen , Jia-Yi Li* (2012) Beyond alpha-synuclein transfer: Pathology propagation in Parkinson’s disease. Trends Molecular Medicine 18: 248-255
19. Christian Hansen 1, Elodie Angot, Ann-Louise Bergström, Jennifer A Steiner, Laura Pieri, Gesine Paul, Tiago F Outeiro, Ronald Melki, Pekka Kallunki, Karina Fog, Jia-Yi Li*, Patrik Brundin* (2011) α-synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. Journal of Clinical Investigation 121: 715-725.
20. Jia-Yi Li , Elisabet Englund, Håkan Widner, Stig Rehncrona, Anders Björklund, Olle Lindvall, Patrik Brundin (2010) Characterization of Lewy body pathology in 12- and 16-year old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Movment Disorders 25:1091-1096.
21. Laurent Roybon , Tord Hjalt, Simon Stott, Francois Guillemot, Jia-Yi Li*, Patrik Brundin* (2009) Neurogenin 2 directs hippocampal granule neurogenesis through a NeuroD1-controlled mechanism of cell-cycle exit and neuronal commitment. PloS One. 4: e4779.
22. Laurent Roybon* , Tomas Deierborg, Patrik Brundin, Jia-Yi Li (2009) Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis. European Journal Neuroscience 29: 232-243.
23.Ruben Smith , Karl Bacos, Valentina Fedele, Denis Soulet, Helena A Walz, Stefanie Obermüller, Anders Lindqvist, Maria Björkqvist, Pontus Klein, Patrik Onnerfjord, Patrik Brundin, Hindrik Mulder, Jia-Yi Li * (2009) Mutant huntingtin interact with beta-tubulin and disrupts vesicular transport and insulin secretion. Human Molecular Genetics 18:3942-3954.
24. Jia-Yi Li., Englund E, Holton J.L., Soulet D., Hagell P., Lees A.J., Lashley T., Quinn N.P., Rehncrona S., Björklund A., Widner H., Revesz T., Lindvall O. and Brundin P* (2008) Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nature Medicine 14: 501-503.
25. Laurent Roybon* , Zhi Ma, Fredrik Asztely, Anna Fosum, Sten Eirik W Jacobsen, Patrik Brundin, Jia-Yi Li (2006) Failure of transdifferentiation of adult hematopoietic stem cells into neurons. Stem Cells 24: 1594-1604.
26. Anke Brederlau , Ana Sofia Correia, Sergey V Anisimov, Muna Elmi, Gesine Paul, Laurent Roybon, Asuka Morizane, Filip Bergquist, Ilse Riebe, Ulf Nannmark, Manolo Carta, Erik Hanse, Jun Takahashi, Yoshiki Sasai, Keiko Funa, Patrick Brundin, Peter S Eriksson* Jia-Yi Li* (2006) Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson’s disease: effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24: 1433-1440
