張研

北京大學生命科學學院教授，北京大學麥戈文腦研究所研究員。 ^[2]  國家傑出青年科學基金獲得者。2003年在McGill大學獲博士學位。她主要從事神經退行性疾病研究，近年來在阿爾茨海默氏症中神經元凋亡及澱粉樣沉積的代謝途徑研究方面取得了令人矚目的研究成果 ^[3]  。利用人類原代神經元為模型研究神經退行性疾病，採用細胞內顯微注射系統，將外源性蛋白及表達質粒引入細胞等方法分析胞內澱粉樣沉積毒性及其作用通路，為澱粉樣沉積導致阿爾茨默症的發病機制提供了新的見解。發現並純化內源性半胱氨酸蛋白酶抑制因子；提出朊蛋白的細胞保護假説。在此基礎上，篩選並研究了一系列可以對抗細胞內澱粉樣沉積毒性的物質；發現了包含甘丙肽和嗎啡在內的臨牀應用藥物的細胞保護作用並研究了其作用機制和分子通路；發現並闡明神經細胞納米連接的誘導機制；深入探討了納米連接在神經退行性疾病中的作用；發現家族型老年性痴呆的突變可以導致microRNA調節和神經元早期發育的異常；揭示了軸突起始節部位異常和老年性痴呆的病理關係；提出了在遺傳性AD突變攜帶者中，神經元存在着早期的發育缺陷。近10年來在國際著名的神經生物學和細胞生物學期刊Neuron, PNAS, Cell Reports，Prog Neurobiol, Nat Methods, Nat Protocol, J Cell Biol, Neurosci Biobehav Rev, J Neurosci, Cell Death Differ, Cell Death Dis, JACS, J Cell Sci等發表學術論文50餘篇，先後被引用1000餘次，其中單篇論文最高他引次數近300次。

1. Cell death in neurodegenerative diseases神經退行性疾病中的細胞死亡機制研究

2. Alzheimer's disease: amyloid toxicity and metabolism, neuronal polarity and biomarkers

老年性痴呆症中的澱粉樣蛋白毒性和代謝，神經元極性和生物標記物研究

3. Cell-cell communication in physiological and stress conditions

在正常和應激條件下的細胞間交流研究 ^[1] 

1999 - 2003 , 理學博士 , Neurology and Neurosurgery , McGill University

1997 - 1999 , 理學碩士 , Neuroscience , Carleton University

1993 - 1997 , 理學學士 , Psychology , Peking University ^[1] 

2018年1月12日，張研獲得“中國青年女科學家”榮譽稱號。 ^[4] 

張研，2007年入選教育部新世紀優秀人才計劃，2011年獲得北京大學綠葉生物醫藥傑出青年學者獎，2014年獲國家自然科學基金委傑出青年基金資助 ^[3]  。

1. Finci LI, Krüger N, Sun X, Zhang J, Chegkazi M, Wu Y, Schenk G, Mertens HDT, Svergun DI,Zhang Y*, Wang J-H*, Meijers R* ,The crystal structure of netrin-1 in complex with DCC reveals the bi-functionality of netrin-1 as a guidance cue, Neuron , 2014 , 83: 839-849

2. Sun X, Wu Y, Gu M,Zhang Y* ,MiR-342-5p Decreases Ankyrin G Level in Alzheimer’s Disease Transgenic Mouse Models, Cell Reports , 2014 , 6: 264-270

3. Tian N, Cao Z,Zhang Y* ,MiR-206 Decreases BDNF Level in AD Transgenic Mouse Model, Neurosci Bull , 2013 , 20: 191-197

4. You Y,Zhang Y* ,Desflurane Accelerates Neuronal Cytotoxicity of Aβ by Downregulating miR-214, Neurosci Lett , 2013 , 554: 28-33

5. Yan H, Guan X, Wang L, Tan J, Wang G, An Y,Zhang Y* ,A point mutation in ε-sarcoglycan induces inherited myoclonus dystonia syndrome in a Chinese family., Int J Clin Exp Med , 2013 , 6: 289-293

6. Yan H, Xu T, Zhao H, Lee K-C, Wang H-Y,Zhang Y* ,Isoflurane increases neuronal cell death vulnerability by downregulating miR-214, PLoS One , 2013 , e55276. DOI:10.1371/journal.pone.0055276.

7. Chen Q, Sun X, Zhou X-H, Liu J-H, Wu J,Zhang Y*, Wang J-H* ,N-terminal horseshoe conformation of DCC is functionally required for axon guidance and may be shared by other neural receptors, J Cell Sci , 2013 , 126: 186-195

8. Du Y, Wang Q,Zhang Y, Wu X-H, Li L* ,Perceived target-masker separation unmasks responses of lateral amygdala to the emotionally conditioned target sounds in awake rats, Neuroscience , 2012 , 225: 249-257

9. Qin X, Lv J, Cui J, Fang X,Zhang Y* ,Curcumin protects against staurosporine toxicity in rat neurons, Neurosci Bull , 2012 , 28: 606-610

10. Hejjaoui M, Butterfield S, Fauvet B, Vercruysse F, Cui J, Dikiy I, Prudent M, Olschewski, Diana;Zhang Y, Eliezer D, Lashuel H* ,Elucidating the role of C-terminal post-translational modifications using protein semisynthesis strategies: α-synuclein phosphorylation at tyrosine 125, JACS , 2012 , 134: 5196-5210

11. Sun X, Meng X, Zhang J, Li Y, Wang L, Qin X, Sui N,Zhang Y* ,GABA attenuates amyloid toxicity by downregulating its endocytosis and improves cognitive impairment, J Alzheimer Dis , 2012 , 30: 1-15

12. Yang B, Sun X, Lashuel H andZhang Y* ,Reactive oxidative species is involved in enhanced amyloid toxicity in APP/PS1 mouse neurons, Neurosci Bull , 2012 , 28: 233-239

13. Sun X, Wang Y, Zhang J, Tu J, Wang X-J, Su X-D, Wang L,Zhang Y* ,Tunneling-nanotube direction determination in neurons and astrocytes, Cell Death Dis , 2012 , 3: e438. DOI: 10.1038/cddis.2012.177

14. Cui J, Wang Y, Dong Q, Wu S, Xiao X, Hu J, Chai Z* andZhang Y* ,Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70, J Neurosci , 2011 , 31: 16277-16240

15.Zhang Y* ,Tunneling-nanotube: A new way of cell-cell communication, Comm Integ Biol , 2011 , 4: 324-325

16.Zhang Y* and Lee D ,Sink hypothesis and therapeutic strategies for attenuating Abeta levels, Neuroscientist , 2011 , 17: 163-173

17. Wang Y, Cui J, Sun X andZhang Y* ,Tunneling-nanotube development in astrocytes depends on p53 activation, Cell Death Differ , 2011 , 18: 732-742

18. Qin XY, Cui J andZhang Y* ,Coeloglossum viride var. bracteatum extract protects against amyloid toxicity in rat prefrontal cortex neurons, Int J Clin Exp Med , 2010 , 3: 88-94

19. Cui J, Chen Q, Yue X, Jiang X, Gao GF*, Yu L* andZhang Y* ,Galanin protects against intracellular amyloid toxicity in human primary neurons, J Alzheimer Dis , 2010 , 19: 529-544

20. Wang XJ, Cao Q, Liu X, Wang KT, Mi W,Zhang Y, Li LF, LeBlanc AC* and Su XD* ,Crystal structures of human caspase 6 reveral a new mechanism for intramolecular cleavage self-activation, EMBO Report , 2010 , 11-841-847

21.Zhang Y*, Xiong W, Lin X, Ma X and Yu L ,Roles of mu-opioid receptor phosphorylation in opioid tolerance and dependence, Neurosci Biobehav Rev , 2009 , 33: 1192-1197

22. Qin XY, Cheng Y, Cui J,Zhang Yand Yu L* ,Potential protection of curcumin against amyloid beta-induced toxicity on cultured rat prefrontal cortical neurons, Neurosci Lett , 2009 , 463: 158-161

23. Hou J, Cui J, Yu L andZhang Y* ,Intracellular amyloid induces impairments on electrophysiological properties of cultured human neurons, Neurosci Lett , 2009 , 462: 294-299

24.Zhang Y* and Yu L* ,Single-cell microinjection technology in cell biology, BioEssays , 2008 , 30: 606-610.

25. Chen Q, Cui J,Zhang Y* and Yu L* ,Prolonged morphine application modulates Bax and Hsp70 levels in primary rat neurons, Neurosci Lett , 2008 , 441: 311-314.

26.Zhang Y*, Chen Q and Yu L* ,Morphine: a protective or destructive role in neurons?, Neuroscientist , 2008 , 14: 561-570

27. Cui J, Chen Q, Yu L andZhang Y* ,Chronic morphine application is protective against cell death in primary human neurons, NeuroReport , 2008 , 19: 1745-1749

28.Zhang Y* and Yu L* ,Microinjection as a tool of mechanical delivery, Curr Opin Biotech , 2008 , 19: 506-510

29.Zhang Y* ,Microinjection Technique and Protocol to Single Cells, Nat Protocols , 2007 , DOI: 10.1038/nprot.2007.487

30. Guo H, Petrin D,Zhang Y, Bergeron C, Goodyer C and LeBlanc A* ,Caspase-1 activation of caspase-6 in human apoptotic neurons, Cell Death Differ , 2006 , 13: 285-292.

31. Roucou X, Giannopoulos PN,Zhang Y, Jodoin J, Goodyer C and LeBlanc A* ,Cellular prion protein inhibits proapoptitic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells, Cell Death Differ , 2005 , 12: 783-795.

32. Tounekti O,Zhang Y, Goodyer C and LeBlanc A* ,Caspase inhibitory factor is mediated by a cysteinyl protease activity, J Neurochem , 2004 , 89: 561-568.

33.Zhang Y, Beitel L, Goodyer C, Trifiro M and LeBlanc A* ,Estrogen and androgen protect against intracellular amyloid beta toxicity, J Neurosci , 2004 , 24: 5315-5321.

34.Zhang Y, Guo Y, Bounhar Y, Roucou X, Goodyer C and LeBlanc A* ,p75NTR protects against extracellular amyloid beta toxicity in human neurons, J Neurosci , 2003 , 23: 7385-7394.

35. Roucou X, Gou Q,Zhang Y, Bounhar Y, Goodyer C and LeBlanc A* ,Cytosolic PrP protects against Bax-mediated cell death in human neurons, J Biol Chem , 2003 , 278: 40877-40881.

36.Zhang Y, McLauglin R, Vereker E, Goodyer C and LeBlanc A* ,Selectively cytotoxicty of intracellular amyloid beta peptide1-42 through p53 and Bax in cultured primary human neurons, J Cell Biol , 2002 , 156: 519-529.

37. Bounhar Y,Zhang Y, Papasopulos M, Turcotte B, Goodyer C and leBlanc A* ,Prion protein protects human neurons against Bax-mediated cell death, J Biol Chem , 2001 , 276: 39145-39149.

38.Zhang Y, Tounekti O, Akerman B, Goodyer C and LeBlanc A* ,17-beta-estradiol induces an inhibitor of active caspases, J Neurosci , 2001 , 21: RC176, 1-6.

39.Zhang Y, Goodyer C and LeBlanc A* ,Selective and protracted apoptosis in human primary neurons microinjected with active caspase-3, -6, -7 and –8, J Neurosci , 2000 , 20: 8384-8389.

40.Zhang Yand Wu SH* ,Long-term potentiation in the dorsal nucleus of the lateral lemniscus and inferior colliculus of rats, Hearing Res , 2000 , 147: 92-103.

41. Zuohong Xue* andZhang Y,Psychological selection methods for winter-over members of the Chinese National Antarctiv Research Expedition, Chinese J Polar Res , 1998 , 10: 49-58.

42. Zuohong Xue*,Zhang Y, Yao Z and Quanfu Xue ,An investigation of physiological changes in winter-over members of Zhongshan Station, Chinese J Polar Res , 1998 , 10: 139-143.

43.Zhang Yand Zuohong Xue* ,Recent studies on human physiology and psychology in Antarctica, Acta Scientiarum Naturalium , 1998 , 34: 125-136.

44. Zuohong Xue*,Zhang Y, Yao Z and Quanfu Xue ,A study of the personality and psychological characteristics of winter-over members in the Antarctic Great Wall Station, Chinese J Polar Res , 1997 , 9: 207-213.

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