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刘磊教授课题组研究方向为细胞死亡、衰老的分子机制及药物干预。在神经元坏死的分子机制方面，建立了世界上首个钙超载介导的神经元坏死的果蝇模型，通过遗传筛选发现了表观遗传通路介导神经元坏死的新机制(PNAS， 2014)；揭示了神经元坏死过程中细胞核皱缩的分子机制、坏死细胞导致周围细胞死亡的方式及线粒体、自噬对细胞坏死的影响 (CellDeath and Disease, 2013，2021；PLoS Genetics, 2016；Journalof Cell Science, 2016； Scientific Reports, 2017)。发现了慢性钙超载导致细胞死亡新的分子机制及通路(CellDeath and Differentiation, 2016)，该通路可能参与了帕金森病等疾病的病理过程。在干预细胞凋亡方面，发现特拉唑嗪具有抗细胞凋亡作用，其分子机制是通过激活磷酸甘油激酶及下游Hsp90实现的(NatureChemical Biology, 2015)。同时，特拉唑嗪可提高糖代谢效率、改善帕金森病模型动物病理表型，这种神经元的保护作用获得了超过二十万患者的流行病数据分析的支持(JCI, 2019;JAMA Neurology, 2021）。获得包括科技部重大专项973、基金委重点项目、面上项目等资金支持。获得4项药物专利授权，相关研究已进入临床前试验阶段。
1. 项目名称：研发延缓和逆转血管老化药物
项目来源：科技部“主动健康及老龄化应对”重点项目/编号:2020YFC2008004
项目经费： 总经费436万元 (本课题组承担270万元)
项目起讫时间：2020年12月1日 到2023年11月31日
项目完成人： 刘磊
2. 项目名称：钙超载对帕金森病模型中自噬功能的作用及机制研究
项目来源： 北京市教育委员会2020年度科技计划重点项目
项目经费： 80万元
项目起讫时间：2020年1月1日 到2022年12月31日
项目完成人： 刘磊
本课题组感兴趣衰老相关的分子机制研究。包括大脑加速衰老是如何发生的？如何干预衰老过程？神经元慢性钙超载如何参与病理过程？如何用小分子药物、多肽药物、或基因治疗药物干预帕金森病、老年痴呆症、青光眼、脑小血管？
1. Yanyan Cao, Kai Liu, Ying Xiong, Chunyue Zhao* and Lei Liu* (2021) (* Corresponding author) Increased expression of fragmented tRNApromoted neuronal necrosis. Cell Death and Disease, 12:823 (IF:8.47)
2. Jacob ESimmering, Michael JWelsh, Lei Liu, Nandakumar SNarayanan, AntonPottegård (2021) Association of Glycolysis-Enhancing α-1 BlockersWith Risk of Developing Parkinson Disease. JAMANeurology 78(4):407-413 (IF:18.32)
3. Rong Cai, Yu Zhang, Jacob E.Simmering, Jordan L. Schultz, Yuhong Li, Irene Fernandez-Carasa,Antonella Consiglio, Angel Raya, Philip M. Polgreen, Nandakumar S. Narayanan,Yanpeng Yuan, Zhiguo Chen, Wenting Su, Yanping Han, Chunyue Zhao, Lifang Gao,Xunming Ji, Michael J. Welsh*and Lei Liu* Enhancing glycolysisattenuates Parkinson’s disease progression in models and clinical databases. TheJournal of Clinical Investigation,129(10):4539-4549. (IF:14.81)
4. Ye Lei，Kai Liu, Lin Hou, Lianggong Ding,Yuhong Li and Lei Liu* (2017) Smallchaperons and autophagy protected neurons from necrotic cell death. ScientificReports, 7(1):5650. (IF: 4.38)
5. Lianggong Ding, Ye Lei, YanpingHan, Yuhong Li, Xunming Ji* and Lei Liu* (2016) Vimar is a novelregulator of mitochondrial fission through Miro. PLoS Genetics, 12(10):e1006359. (IF: 5.92)
6. Lin Hou, Kai Liu, Yuhong Li, ShuangMa, Xunming Ji* and Lei Liu * (2016) Necrotic pyknosis is amorphologically and biochemically distinct event from apoptotic pyknosis. Journalof Cell Science, 129：3084-3090. (IF: 5.28)
7. Yu Zhang#, Rong Cai#, Rui Zhou,Yuhong Li* and Lei Liu* (2016). Tousled-like kinase mediates a new typeof cell death in Drosophila. CellDeath and Differentiation, 23:146-57. (IF=15.8)
8. Xinping Chen#, Chunyue Zhao#,Xiaolong Li#, Tao Wang#, Yizhou Li, Cheng Cao, Yuehe Ding, Mengqiu Dong,Lorenzo Finci, Jia-huai Wang*, Xiaoyu Li* and Lei Liu* (2015) Terazosinactivates Pgk1 and Hsp90 to promote stress resistance. Nature ChemicalBiology 11: 19-25. (IF: 15.04)
9. Kai Liu, Lianggong Ding, YuhongLi, Hui Yang, Chunyue Zhao, Ye Lei, Shuting Han, Wei Tao, Dengshun Miao, HermannSteller, Michael Welsh* and Lei Liu* (2014). Neuronal necrosis isregulated by a conserved chromatin-modifying cascade. PNAS 111: 13960-13965. (IF: 11.21)
10. Yong Yang, Lin Hou, Yuhong Li, Jianquan Ni and Lei Liu*(2013) Neuronal necrosis and spreading death in Drosophila genentic model. Cell Death & Disease 4 e723. (IF: 8.47)
11. Kai Liu, Yuhong Li and Lei Liu* (2013） Chapter 15: Modeling calcium-overloadmediated necrosis in Drosophila. Methods in Molecular Biology1004:203-13. (IF: 13.9)
12. Yishan Sun,Lei Liu,YehudaBen-Shahar, Julie S. Jacobs,Daniel F.Eberl and Michael J.Welsh* (2009). TRPA channels distinguish gravity sensing fromhearing in Johnston's organ. PNAS 106:13606-13611. (IF:11.21)
13. David A. Stoltz, Egon A.Ozer, Peter J. Taft, Marilyn Barry, Lei Liu, Peter J. Kiss, Thomas O.Moninger, Matthew R. Parsek, and Joseph Zabner* (2008). Drosophila areprotected from Pseudomonas aeruginosa lethality by transgenic expression ofparaoxonase-1. Journal of Clinical Investigation 118(9):3123–3131. (IF:14.81)
14. Lei Liu, Yuhong Li, Runping Wang, Chong Yin, Qian Dong, Huey Hing, ChangsooKim and Michael J. Welsh*(2007) Drosophila Hygrosensation requires the TRP channels water witch and nanchung. Nature 450:294-298. (IF:45.819)
15. Lei Liu, A. Soren Leonard, David G.Motto, Margaret A. Feller, Margaret P. Price, Wayne A. Johnson and Michael J.Welsh* (2003). Contribution of DrosophilaDEG/ENaC genes to salt taste. Neuron 39: 133-146. (IF:16.319)
16. Lei Liu, OlenaYermolaieva, Wayne A. Johnson, Francois M. Abboud, and Michael J. Welsh*(2003). Identification and function of thermosensory neurons in Drosophila larvae. Nature Neuroscience 6(3):267-273. (IF:21.403)
17. Lei Liu, Wayne A. Johnson, and MichaelJ. Welsh* (2003). Drosophila DEG/ENaC pickpocket genes are expressed in thetracheal system, where they may be involved in liquid clearance. PNAS 100(4):2128-2133. (IF:11.21)
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