Biography

Education

09/2007-06/2010  Tongji Medical College, Huazhong University of Science and Technology. Doctor’s degree in neurology.

09/2004-06/2007  Tongji Medical College, Huazhong University of Science and Technology. Master’s degree in neurology.

09/1999-06/2004  Weifang Medical College. Batcher’s degree in clinical medicine.

Academic and professional appointments

11/2017-Now  Renmin Hospital of Wuhan University, Department of Neurology. Professor, chief physician.

10/2016-02/2015  Emory University, Department of Pathology and Laboratory Medicine. Assistant professor.

02/2012-01/2015  Emory University, Department of Pathology and Laboratory Medicine. Postdoctoral Fellow.

11/2016-10/2017 Renmin Hospital of Wuhan University, Department of Neurology. Professor, associate chief physician.

07/2010-01/2012 Renmin Hospital of Wuhan University, Department of Neurology. Professor, attending physician.

Research

Dr. Zhang's research focuses on disease proteins that form pathological inclusions in neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). His work demonstrated that the fragmentation, modification by homocysteine and DOPEGAL, and other post-translational modifications of Tau and alpha-synuclein promote the aggregation and propagation of these pathologic proteins, leading to neurodegeneration. Furthermore, his group demonstrated that endogenous and exogenous seeds trigger the aggregation of Tau and alpha-synuclein. He is also interested in the molecular mechanisms underlying synaptic dysfunction and neuronal injury in neurodegenerative diseases. His work supports that the protease asparagine endopeptidase (AEP) plays a key role in mediating AD and PD pathogenesis. He has authored or co-authored over 100 professional publications in the field of neurobiology, most of which are on Parkinson's disease and Alzheimer's disease.

Representative  Publications

1. Xiang J^#, Tao Y^#, Xia Y^#, Luo S, Zhao Q, Li B, Zhang X, Sun Y, Xia W, Zhang M, Kang SS, Ahn EH, Liu X, Xie F, Guan Y, Yang JJ, Bu L, Wu S, Wang X, Cao X, Liu C, Zhang Z^*, Li D^*, Ye K^*. Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies. Cell, 2023, 186(16):3350-3367.

2. Zhang X^#, Tang L^#, Yang J, Meng L, Chen J, Zhou L, Wang J, Xiong M, Zhang Z^*. Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease. Nature Communications, 2023, 14(1):6670.

3. Meng L, Liu C, Li Y, Chen G, Yu T, Pan L, Zhang X, Zhou L, Guo T, Yuan X, Zhang Z, Liu C, Xiong M, Zhang Z^*. The yeast prion protein Sup35 initiates α-synuclein pathology in mouse models of PD. Science Advances, 2023, in press.

4. Meng L, Liu C, Liu M, Chen J, Liu C, Zhang Z, Chen G, Zhang Z^*. The yeast protein Ure2p triggers Tau pathology in a mouse model of tauopathy. Cell reports, 2023, in press.

5. Yan M^#, Tang L^#, Dai L, Lei C, Xiong M, Zhang X, He M, Tian Y, Xiong J, Ke W, Zhang Z, Zhang C, Deng X, Zhang Z^*. Cofilin promotes tau pathology in Alzheimer’s disease. Cell Reports, 2023, 42(2):112138.

6. Dai L^#, Wang J^#, Zhang X, Yan M, Zhou L, Zhang G, Meng L, Chen L, Cao X, Zhang Z, Wang G^*, Zhang Z^*. 27-Hydroxycholesterol Drives the Spread of α-Synuclein Pathology in Parkinson's Disease. Movement Disorders, 2023. doi: 10.1002/mds.29577.

7. Zhou L^#, Guo T^#, Meng L, Zhang X, Tian Y, Dai L, Niu X, Li Y, Liu C, Chen G, Liu C, Ke W, Zhang Z, Bao A*, Zhang Z^*. N-homocysteinylation of α-synuclein promotes its aggregation and neurotoxicity. Aging Cell, 2023: e13745.

8. Pan L^#, Li C^#, Meng L, Tian Y, He M, Yuan X, Zhang G, Zhang Z, Xiong J, Chen G, Zhang Z^*. Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease. Brain, 2022, 145(10):3454-3471.

9. Zhang G^#, Meng L^#, Wang Z, Peng Q, Chen G, Xiong J, Zhang Z^*. Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer's disease. Molecular Neurodegeneration, 2022, 17(1):12.

10. Meng L^#, Zou L, Xiong M, Chen J, Zhang X, Yu T, Li Y, Liu C, Chen G, Wang Z, Ye K, Zhang Z^*. A synapsin Ⅰ cleavage fragment contributes to synaptic dysfunction in Alzheimer's disease. Aging Cell, 2022, 21(5):e13619.

11. Kang SS^#, 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. Nature Structural & Molecular Biology, 2022, 29(4):292-305.

12. Yuan X^#, Yang Y, Liu C, Tian Y, Xia D, Liu Z, Pan L, Xiong M, Xiong J, Meng L, Zhang Z, Ye K, Jiang H, Zhang Z^*. Fine Particulate Matter Triggers α-Synuclein Fibrillization and Parkinson-like Neurodegeneration. Movement Disorders, 2022, 37(9):1817-1830.

13. Yan M^#, Xiong M, Dai L, Zhang X, Zha Y, Deng X, Yu Z, Zhang Z*. Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease. NPJ Parkinson's Disease, 2022, 8(1):1.

14. Xiong M^#, Zou L, Meng L, Zhang X, Tian Y, Zhang G, Yang J, Chen G, Xiong J, Ye K, Zhang Z*. A γ-adducin cleavage fragment induces neurite deficits and synaptic dysfunction in Alzheimer's disease. Progress in Neurobiology, 2021, 203:102074.

15. Zhang Z^#, Li XG^#, Wang ZH, Song M, Yu SP, Kang SS, Liu X, Zhang Z, Xie M, Liu GP, Wang JZ^*, Ye K^*. δ-Secretase-cleaved Tau stimulates Aβ production via upregulating STAT1-BACE1 signaling in Alzheimer's disease. Molecular Psychiatry, 2021, 26(2):586-603.

16. Zhang X^#, Zou L^#, Meng L, Xiong M, Pan L, Chen G, Zheng Y, Xiong J, Wang Z, Duong DM, Zhang Z, Cao X, Wang T, Tang L, Ye K, Zhang Z*. Amphiphysin I cleavage by asparagine endopeptidase leads to tau hyperphosphorylation and synaptic dysfunction. Elife, 2021, 10:e65301.

17. Zhang Z^#, Kang SS, Liu X, Ahn EH, Zhang Z, He L, Iuvone PM, Duong DM, Seyfried NT, Benskey MJ, Manfredsson FP, Jin L*, Sun YE, Wang JZ^*, Ye K^*. Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease. Nature Structural & Molecular Biology, 2017, 24(8):632-642.

18. Zhang Z^#, Obianyo O^#, Dall E^#, Du Y, Fu H, Liu X, Kang SS, Song M, Yu SP, Cabrele C, Schubert M, Li X, Wang JZ^*, Brandstetter H^*, Ye K^*. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease. Nature Communications, 2017, 8:14740.

19. Zhang Z^#, Song M, Liu X, Su Kang S, Duong DM, Seyfried NT, Cao X, Cheng L, Sun YE^*, Ping Yu S, Jia J^*, Levey AI, Ye K^*. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease. Nature Communications, 2015, 6:8762.

20. Zhang Z^#, Song M, Liu X, Kang SS, Kwon IS, Duong DM, Seyfried NT, Hu WT, Liu Z, Wang JZ, Cheng L^*, Sun YE, Yu SP, Levey AI, Ye K^*. Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease. Nature Medicine, 2014, 20, 1254-1262.