叶克强-生命健康学院

叶克强Keqiang Ye

生物学系系主任、讲席教授

透过现象看本质，寻找复杂世界的简单法则！

个人主页

研究领域

主要研究方向包括：

1. 神经退行性疾病发病机制及早期诊断；

2. 小分子神经退行性疾病新药物的开发及研究；

3. 药物的筛选，化学合成，改造及药物设计。

Molecular mechanisms in neurodegenerative diseases, early diagnosis and drug development.

个人简介

叶克强教授，深圳理工大学生命健康学院系主任、讲席教授，曾任美国埃默里大学终身教授、博士生导师。深耕神经退行性疾病机制、早期诊断及药物研发数十年，是世界公认的小分子化合物治疗研发的领军科学家之一。获得国家自然科学基金委员会、美国国立卫生研究院、国防部科学基金会和美国癌症协会/基金会等重要基金机构资助，总金额逾1.59亿元。截至2024年7月发表论文300余篇，包括Nature（2篇）、Cell（3篇）、Nature Medicine、Nature Neuroscience等高影响因子72篇，H因子78，被引次数达22332次；申报美国及世界发明专利24项，获批19项，多项已被各国公司购买并转化，其研发的阿尔兹海默症小分子新药BrAD-R13分别在2019年、2023年取得美国FDA及中国国家药监局药品评审中心（CDE）的“临床试验默示许可”。他在世界上首次发明了a-突柱核蛋白示踪剂解决了帕金森病PET影像学诊断这一世界难题，并开创性地提出了女性绝经后FSH（卵泡刺激素）增加激活C/EBPb/AEP通路导致女性更容易得老年痴呆症理论！

学习工作经历

学习经历

1993-1998，美国埃默里大学，生物化学和细胞生物学，博士

1990-1993，北京大学，化学系，硕士

1986-1990，吉林大学，化学系，学士

工作经历

2021-至今，深圳理工大学，生命健康学院生物学系，系主任、讲席教授

2001-2021，美国埃默里大学，医学院病理系，历任助理教授、副教授、终身教授；

1998-2001，约翰霍普金斯大学，医学院神经生物学系，博士后，合作导师：Solomon H. Snyder, MD

学术成果

国际影响力

2021年，全球前2%顶尖科学家

2023年，全球前2%科学家之一（进入终身科学影响力排行榜）

2023年，“Alzheimer's Association International Conference® (AAIC®)”, Amsterdam, Netherlands, July 16-20th, 2023.

2023年，“ 12th General Meeting of the International Proteolysis Society, at the National University of Singapore)”, Singapore, June 24-29th, 2023.

2023年，The 6th NO-Age/AD meeting on ageing and dementia, Norway, 24-26th, Sep. 2023.

2023年，“The 16 Annual Meeting of Chinese Neuroscience Society &The 2 CJK International Meeting”, Zhuhai, China, July 27-30th, 2023.

2023年，“3rd Hefei International Summit on Alzheimer’s Disease (Aging and Brain Forum)”, Hefei, China, September 21-23th, 2023.

2023年，“Sino-German Workshops on Early Diagnostic Markers in Preclinical Alzheimer's Disease”, Haikou, Hainan, China, October 8-10th, 2023.

2022年至今，Elife，Review Editor.

所获荣誉

2003年，美国杰出青年科学家奖一等奖

2004年，美国优秀癌症研究学者奖国家一等奖

2011年，教育部“长江学者”讲座教授

2017年，国家重大人才工程特聘专家

2021年，深圳市海外高层次A类人才

科研成果

2021年全职加入深圳理工大学后，获批并主持国自然重点项目、国自然外国资深学者项目、国自然重大项目（课题负责人）、深圳市高层次人才团队项目，并参与国家重点研发计划项目1项，广东省区域联合基金项目1项。

先后共发表论文260余篇，H因子77，被引次数共计21722余次。其中高影响因子的文章包括Nature杂志2篇，Cell杂志3篇，以及Nature Medicine, Cancer Cell, Nature Neuroscience, Nature Cell Biology, Nature Structure & Molecular Biology, Nature Communications, Cell Research等。获批13项发明专利。

叶克强教授于2015年联合创立上海博芮健制药有限公司，专注于中枢神经系统疾病领域的创新药和诊断方法开发，产品管线包括一个临床阶段的创新药，两个临床前阶段已立项IND的小分子药物以及一项PET-CT诊断试剂，适应症包括阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化（ALS)等。博芮健自主研发的Ⅰ类创新药BrAD-R13片（一款小分子TrkB受体激动剂产品），已获得美国FDA以及中国药品监督管理局药品审评中心的临床试验默示许可，拟用于轻、中度AD治疗。另一款自主研发的PD早期诊断新型PET示踪剂“[18F]-F0502B”，正在进行准备进入临床阶段。

代表性论文

1. Wang G, Han J, Meng X, Kang SS, Liu X, Sun YE, Luo Q,Ye K.Zein-Based Nanopartic les Improve the Therapeutic Efficacy of a TrkB Agonist toward Alzheimer's Disease.ACS Chem Neurosci.2023, Sep 6;14(17):3249-3264.

2. Qian Z, Li B, Meng X, Liao J, Wang G, Li Y, Luo Q,Ye K.Inhibition of asparagine end opeptidase (AEP) effectively treats sporadic Alzheimer's disease in mice.Neuropsychopharm acology.2024,Feb;49(3):620-630.

3. Xiang J, Xia Y, Luo S, Zhang Z,Ye K.Protocol for screening α-synuclein PET tracer cand idates in vitro and ex vivo.STAR Protoc.2023,Dec 19;5(1):102788.

4. Xiang J, Zhang Z,Ye K.A promising PET tracer candidate targeting α-synuclein inclusions. Clin Transl Med.2023, Sep;13(9):e1408.

5. Ahn EH, Liu X, Alam AM, Kang SS,Ye K.Helicobacter hepaticus augmentation triggers Dopaminergic degeneration and motor disorders in mice with Parkinson's disease.Mol Psychiatry.2023Mar;28(3):1337-1350.

6. Xiong J, Kang SS, Wang M, Wang Z, Xia Y, Liao J, Liu X, Yu SP, Zhang Z, Ryu V, Yuen T, Zaidi M,Ye K.FSH and ApoE4 contribute to Alzheimer's disease-like pathogenesis via C/EBPβ/δ-secretase in female mice.Nat Commun.2023,Oct 18;14(1):6577.

7. Xia Y, Xiao Y, Wang ZH, Liu X, Alam AM, Haran JP, McCormick BA, Shu X, WangX,Ye K.Bacteroides Fragilis in the gut microbiomes of Alzheimer's disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice.Nat Commun.2023, Sep 6;14(1):5471.

8. Xiong J, Zhang Z,Ye K.C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis.Neurosci Bull.2023,Jul; 39(7):1173-1185.

9. Xiang, J.; Tao, Y.; Xia, Y.; Luo, S.; Zhao, Q.; Li, B.; Zhang, X.; Sun, Y.; Xia, W.; Zhang,M.; Kang, S. S.; Ahn, E. H.; Liu, X.; Xie, F.; Guan, Y.; Yang, J. J.; Bu, L.; Wu, S.; Wang, X.; Cao, X.; Liu, C.; Zhang, Z.; Li, D.;Ye, K.Development of an alpha-synuclein positron emission tomography tracer for imaging synucleinopathies.Cell2023, 186, 3350-3367 e3319.

10. Xiong, J.; Liao, J.; Liu, X.; Zhang, Z.; Adams, J.; Pacifici, R.;Ye, K.A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin.Nat Commun2022,13, 4820.

11. Xiong, J.; Kang, S. S.; Wang, Z.; Liu, X.; Kuo, T. C.; Korkmaz, F.; Padilla, A.; Miyashita, S.; Chan, P.; Zhang, Z.; Katsel, P.; Burgess, J.; Gumerova, A.; Ievleva, K.; Sant, D.; Yu,S. P.; Muradova, V.; Frolinger, T.; Lizneva, D.; Iqbal, J.; Goosens, K. A.; Gera, S.; Rosen,C. J.; Haroutunian, V.; Ryu, V.; Yuen, T.; Zaidi, M.;Ye, K.FSH blockade improves cognition in mice with Alzheimer's disease.Nature2022,603, 470-476.

12. Xia, Y.; Qadota, H.; Wang, Z. H.; Liu, P.; Liu, X.; Ye, K. X.; Matheny, C. J.; Berglund,K.; Yu, S. P.; Drake, D.; Bennett, D. A.; Wang, X. C.; Yankner, B. A.; Benian, G. M.;Ye,K.Neuronal C/EBPbeta/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression.Sci Adv2022,8, eabj8658.

13. Wang, Z. H.; Xia, Y.; Wu, Z.; Kang, S. S.; Zhang, J. C.; Liu, P.; Liu, X.; Song, W.; Huin, V.; Dhaenens, C. M.; Yu, S. P.; Wang, X. C.;Ye, K.Neuronal ApoE4 stimulates C/EBPbeta activation, promoting Alzheimer's disease pathology in a mouse model.Prog Neurobiol2022,209, 102212.

14. Liu, P.; Wang, Z. H.; Kang, S. S.; Liu, X.; Xia, Y.; Chan, C. B.;Ye, K.High-fat diet-induced diabetes couples to Alzheimer's disease through in flammation-activated C/EBPbeta/AEP pathway.Mol Psychiatry2022,19, 1283-1297.

15. Kang, S. S.; Wu, Z.; Liu, X.; Edgington-Mitchell, L.;Ye, K.Treating Parkinson's Diseasevia Activation of BDNF/TrkB Signaling Pathways and Inhibition of Delta-Secretase.Neuroth erapeutics2022,Online ahead of print.

16. Kang, S. S.; Meng, L.; Zhang, X.; Wu, Z.; Mancieri, A.; Xie, B.; Liu, X.; Weinshenker,D.; Peng, J.; Zhang, Z.;Ye, K.Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation.Nat Struct Mol Biol2022,29, 292-305.

17. Chen, G.; Ahn, E. H.; Kang, S. S.; Xia, Y.; Liu, X.; Zhang, Z.;Ye, K.UNC5C Receptor Proteolytic Cleavage by Active AEP Promotes Dopaminergic Neuronal Degeneration in Parkinson's Disease.Adv Sci (Weinh)2022,9, e2103396.

18. Chen, C.; Liao, J.; Xia, Y.; Liu, X.; Jones, R.; Haran, J.; McCormick, B.; Sampson, T. R.;Alam, A.;Ye, K.Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.Gut2022,71, 2233-2252.

19. Yao, Y.; Kang, S. S.; Xia, Y.; Wang, Z. H.; Liu, X.; Muller, T.; Sun, Y. E.;Ye, K.A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.Brain2021,144, 1833-1852.

20. Xia, Y.; Wang, Z. H.; Liu, P.; Edgington-Mitchell, L.; Liu, X.; Wang, X. C.;Ye, K.TrkBreceptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer's disease pathologies.Mol Psychiatry2021,26, 2943-2963.

21. Kang, S. S.; Ahn, E. H.; Liu, X.; Bryson, M.; Miller, G. W.; Weinshenker, D.;Ye, K.ApoE4 inhibition of VMAT2 in the locus coeruleus exacerbates Tau pathology in Alzheimer'sdisease.Acta Neuropathol2021,142, 139-158.

22. Chen, G.; Kang, S. S.; Wang, Z.; Ahn, E. H.; Xia, Y.; Liu, X.; Sandoval, I. M.; Manfredsson, F. P.; Zhang, Z.;Ye, K.Netrin-1 receptor UNC5C cleavage by active delta-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.Sci Adv2021,7.

23. Chen, C.; Zhou, Y.; Wang, H.; Alam, A.; Kang, S. S.; Ahn, E. H.; Liu, X.; Jia, J.;Ye,K.Gut inflammation triggers C/EBPbeta/delta-secretase-dependent gut-to-brain propagation of Abeta and Tau fibrils in Alzheimer's disease.EMBO J2021,40, e106320.

24. Ahn, E. H.; Lei, K.; Kang, S. S.; Wang, Z. H.; Liu, X.; Hong, W.; Wang, Y. T.; Edgington-Mitchell, L. E.; Jin, L.;Ye, K.Mitochondrial dysfunction triggers the pathogenesis of Par kinson's disease in neuronal C/EBPbeta transgenic mice.Mol Psychiatry2021,26, 7838-7850.

25. Kang, S. S.; Liu, X.; Ahn, E. H.; Xiang, J.; Manfredsson, F. P.; Yang, X.; Luo, H. R.; Li les, L. C.; Weinshenker, D.;Ye, K.Norepinephrine metabolite DOPEGAL activates AEP and pathological Tau aggregation in locus coeruleus.J Clin Invest2020,130, 422-437.

26. Wang, Z. H.; Xiang, J.; Liu, X.; Yu, S. P.; Manfredsson, F. P.; Sandoval, I. M.; Wu, S.X.; Wang, J. Z.;Ye, K.Deficiency in BDNF/TrkB Neurotrophic Activity Stimulates delta-Secretase by Upregulating C/EBP beta in Alzheimer's Disease.Cell Rep2019,28, 655-+.27.Wang, Z. H.; Gong, K.; Liu, X.; Zhang, Z. T.; Sun, X. O.; Wei, Z. Z.; Yu, S. P.; Manfredsson, F. P.; Sandoval, I. M.; Johnson, P. F.; Jia, J. P.; Wang, J. Z.;Ye, K.C/EBP beta regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer's disease.Nat Commun2018,9.

28. Chen, C.; Wang, Z.; Zhang, Z.; Liu, X.; Kang, S. S.; Zhang, Y.;Ye, K.The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease.Proc Natl Acad Sci U S A2018,115, 578-583.

29. Zhang, Z.; Obianyo, O.; Dall, E.; Du, Y.; Fu, H.; Liu, X.; Kang, S. S.; Song, M.; Yu, S.P.; Cabrele, C.; Schubert, M.; Li, X.; Wang, J. Z.; Brandstetter, H.;Ye, K.Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease.Nat Commun2017,8, 14740.

30. Zhang, Z.; Kang, S. S.; Liu, X.; Ahn, E. H.; Zhang, Z.; He, L.; Iuvone, P. M.; Duong,D. M.; Seyfried, N. T.; Benskey, M. J.; Manfredsson, F. P.; Jin, L.; Sun, Y. E.; Wang, J.Z.;Ye, K.Asparagine endopeptidase cleaves alpha-synuclein and mediates pathologic activities in Parkinson's disease.Nat Struct Mol Biol2017,24, 632-642.

31. Wang, Z. H.; Liu, P.; Liu, X.; Manfredsson, F. P.; Sandoval, I. M.; Yu, S. P.; Wang, J.Z.;Ye, K.Delta-Secretase Phosphorylation by SRPK2 Enhances Its Enzymatic Activity, Provoking Pathogenesis in Alzheimer's Disease.Mol Cell2017,67, 812-825 e815.

32. Zhang, Z.; Song, M.; Liu, X.; Su Kang, S.; Duong, D. M.; Seyfried, N. T.; Cao, X.; Cheng, L.; Sun, Y. E.; Ping Yu, S.; Jia, J.; Levey, A. I.;Ye, K.Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease.Nature commun2015,6, 8762.

33. Zhang, Z.; Song, M.; Liu, X.; Kang, S. S.; Kwon, I. S.; Duong, D. M.; Seyfried, N. T.;Hu, W. T.; Liu, Z.; Wang, J. Z.; Cheng, L.; Sun, Y. E.; Yu, S. P.; Levey, A. I.;Ye, K.Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease.Nat Med2014,20, 1254-1262.

34. Jang, S. W.; Liu, X.; Yepes, M.; Shepherd, K. R.; Miller, G. W.; Liu, Y.; Wilson, W. D.;Xiao, G.; Blanchi, B.; Sun, Y. E.;Ye, K.A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone.Proc Natl Acad Sci U S A2010,107, 2687-2692.

35. Tang, X. L.; Jang, S. W.; Okada, M.; Chan, C. B.; Feng, Y.; Liu, Y.; Luo, S. W.; Hong,Y.; Rama, N.; Xiong, W. C.; Mehlen, P.;Ye, K.Netrin-1 mediates neuronal survival throughPIKE-L interaction with the dependence receptor UNC5B.Nat Cell Biol2008,10, 698-706.

36. Liu, Z.; Jang, S. W.; Liu, X.; Cheng, D.; Peng, J.; Yepes, M.; Li, X. J.; Matthews, S.; Watts, C.; Asano, M.; Hara-Nishimura, I.; Luo, H. R.;Ye, K.Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase.Mol Cell2008,29, 665-678.

37. Tang, X. L.; Jang, S. W.; Wang, X. R.; Liu, Z. X.; Bahr, S. M.; Sun, S. Y.; Brat, D.; Gutmann, D. H.;Ye, K.Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation.Nat Cell Biol2007,9, 1199-1207.

38. Ahn, J. Y.; Liu, X.; Cheng, D.; Peng, J.; Chan, P. K.; Wade, P. A.;Ye, K.Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD.Mol Cell2005,18, 435-445.39.Rong, R.; Tang, X. L.; Gutmann, D. H.;Ye, K.Neurofibromatosis 2 (NF2) tumor suppress or merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L.Proc Natl AcadSci U S A2004,101, 18200-18205.

40. Ahn, J. Y.; Rong, R.; Liu, X.;Ye, K.PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus.EMBO J2004,23, 3995-4006.

41. Rong, R.; Ahn, J. Y.; Huang, H.; Nagata, E.; Kalman, D.; Kapp, J. A.; Tu, J.; Worley, P.F.; Snyder, S. H.;Ye, K.PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis.Nat Neurosci2003,6, 1153-1161.

42. Ye, K.; Aghdasi, B.; Luo, H. B. R.; Moriarity, J. L.; Wu, F. Y.; Hong, J. J.; Hurt, K. J.;Bae, S. S.; Suh, P. G.; Snyder, S. H. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE.Nature2002,415, 541-544.

43. Ye, K.; Hurt, J.; Wu, F. Y.; Fang, M.; Luo, H. B. R.; Hong, J. J.; Blackshaw, S.; Ferris,C. D.; Snyder, S. H. PIKE: A nuclear GTPase that enhances PI3Kinase activity and is regulated by protein 4.1N.Cell2000,103, 919-930.

44. Ye, K.; Ke, Y.; Keshava, N.; Shanks, J.; Kapp, J. A.; Tekmal, R. R.; Petros, J.; Joshi, H.C. Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells.Proc Natl Acad Sci U S A1998,95, 1601-1606.

英文名	Keqiang Ye	首字母	Y
学系	生物学系	岗位	讲席教授
职称-职务	生物学系系主任、讲席教授	前海外职称-职务	美国埃默里大学终身教授
邮箱	kq.ye@siat.ac.cn	座右铭	透过现象看本质，寻找复杂世界的简单法则！
介绍一	现任深圳理工大学生命健康学院生物学系主任、讲席教授	介绍二	叶克强教授是世界公认的小分子化合物治疗研发的领军科学家之一，是研发小分子化合物治疗神经退行性疾病领域的国际权威。