Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the major cause of dementia globally. It is commonly associated with progressive neuronal loss and cognitive decline. Based on the data from Alzheimer's disease International (ADI), there are currently over 50 million AD cases worldwide, from which approximately 1/5 are Chinese. However, there remains no effective treatment for the great majority of patients. Furthermore, a large number of clinical trials have been discontinued or failed in the past few years. This is due to:1) lack of standard reliable in vitro or in vivo research models; 2) the primary causes of the disease are unknown; 3) current biomarkers cannot effectively support early diagnosis.

We apply a wide range of advanced biochemical, molecular and cell biological, electrophysiological techniques, to study the complex mechanisms during AD progression and ultimately develop new biomarkers and therapeutic strategies. Current research interests include: 1)Develop “all human AD models” based on human iPSC and brain-derived neurotoxic protein aggregates; 2)Dissect the molecular characteristics of highly heterogeneous neurotoxic amyloid β-protein (Aβ) present in human AD brains; 3)Develop new biomarkers targeting to covalently-cross linked Aβ dimers; 4) Discover new pathological, cellular and molecular mechanisms during AD progression using “all human AD models”.

Biography

2019-present, Associate Professor, BCBDI, SIAT at CAS
2014-2019, Postdoctoral Fellow, Department of Neurology, Harvard Medical School/Brigham and Women’s Hospital
2009-2014, PhD, Microbiology, College of Life Sciences, Wuhan University
2005-2009, B.S., Biotechnology, College of Life Sciences, Wuhan University

Selected publications

1.Grant T Corbett, Zemin Wang, Wei Hong, Marti Colom-Cadena, Jamie Rose, Meichen Liao, Adhana Asfaw, Tia C Hall, Lai Ding, Alexandra DeSousa, Matthew P Frosch, John Collinge, David A Harris, Michael S Perkinton, Tara L Spires-Jones, Tracy L Young-Pearse, Andrew Billinton, Dominic M Walsh; PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins; Acta Neuropathologica , 2020, 139: 503–526.

2.Sipian Li, Shuwen Sunchen, Dangui He, Chenhu Qin, Zheng Zuo, Bingzheng Shen, Zhijian Cao, Wei Hong* , Lixia Miao*; ImKTx96, a peptide blocker of the Kv1. 2 ion channel from the venom of the scorpion Isometrus maculates; Peptides , 2020, 123: 170172.

3.Benedikt Zott, Manuel M Simon, Wei Hong , Felix Unger, Hsing-Jung Chen-Engerer, Matthew P Frosch, Bert Sakmann, Dominic M Walsh, Arthur Konnerth; A vicious cycle of beta amyloid-dependent neuronal hyperactivation; Science , 2019, 365(6453): 559-565.

4.Gunnar Brinkmalm#, Wei Hong# , Zemin Wang, Wen Liu, Tiernan T O’Malley, Xin Sun, Matthew P Frosch, Dennis J Selkoe, Erik Portelius, Henrik Zetterberg, Kaj Blennow, Dominic M Walsh; Identification of neurotoxic cross-linked amyloid-beta dimers in the Alzheimer's brain; Brain , 2019, 142(5): 1441-1457.

5. Wei Hong , Zemin Wang, Wen Liu, Tiernan T O’Malley, Ming Jin, Michael Willem, Christian Haass, Matthew P Frosch, Dominic M Walsh; Diffusible, highly bioactive oligomers represent a critical minority of soluble Abeta in Alzheimer's disease brain; Acta Neuropathologica , 2018, 136(1): 19-40.

6.Ming Jin, Brian O’Nuallain, Wei Hong , Justin Boyd, Valentina N Lagomarsino, Tiernan T O’Malley, Wen Liu, Charles R Vanderburg, Matthew P Frosch, Tracy Young-Pearse, Dennis J Selkoe*, Dominic M Walsh*; An in vitro paradigm to assess potential anti-Abeta antibodies for Alzheimer's disease; Nature Communications , 2018, 9(1): 1-13.

7.Zhengyang Zeng#, Runhong Zhang#, Wei Hong# , Yuting Cheng, Huijuan Wang, Yange Lang, Zhenglin Ji, Yingliang Wu, Wenxin Li, Youli Xie*, Zhijian Cao*; Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1; Theranostics , 2018, 8(1): 199-211.

8.Tomas Ondrejcak, Igor Klyubin, Grant T Corbett, Graham Fraser, Wei Hong , Alexandra J Mably, Matthew Gardener, Jayne Hammersley, Michael S Perkinton, Andrew Billinton, Dominic M Walsh, Michael J Rowan; Cellular Prion Protein Mediates the Disruption of Hippocampal Synaptic Plasticity by Soluble Tau In Vivo; J Neurosci , 2018, 38(50):10595-10606.

9.Zemin Wang, Rosemary J Jackson, Wei Hong , Taylor M Walter, Arturo Moreno, Wen Liu, Shaomin Li, Matthew P Frosch, Inna Slutsky, Tracy Young-Pearse, Tara L Spires-Jones, Dominic Walsh; Human Brain-Derived Abeta Oligomers Bind to Synapses and Disrupt Synaptic Activity in a Manner That Requires APP; J Neurosci , 2017, 37(49):11947-11966.

10.Zhengyang Zeng#, Shisong Han#, Wei Hong , Yange Lang, Fangfang Li, Yongxiang Liu, Zeyong Li, Yingliang Wu, Wenxin Li, Xianzheng Zhang*, Zhijian Cao*; A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA; Mol Ther Nucleic Acids , 2016, 5:e295.

11. Wei Hong# , Yange Lang#, Tian Li, Zhengyang Zeng, Yu Song, Yingliang Wu, Wenxin Li, Zhijian Cao; A p7 Ion Channel-derived Peptide Inhibits Hepatitis C Virus Infection in Vitro; J Biol Chem , 2015, 290(38):23254-23263.

12.Shisong Han, Zeyong Li, Jingyi Zhu, Kai Han, Zhengyang Zeng, Wei Hong , Wenxin Li, Huizhen Jia, Yun Liu, Renxi Zhuo, Xianzheng Zhang; Dual-pH Sensitive Charge-Reversal Polypeptide Micelles for Tumor-Triggered Targeting Uptake and Nuclear Drug Delivery; Small , 2015, 11(21): 2543-2554.

13. Wei Hong , Tian Li, Yu Song, Runhong Zhang, Zhengyang Zeng, Shisong Han, Xianzheng Zhang, Yingliang Wu, Wenxin Li, Zhijian Cao; Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1; Antiviral Research , 2014, 102:1-10.

14.Yu Song, Ke Gong, Hong Yan, Wei Hong , Le Wang, Yingliang Wu, Wenhua Li*, Wenxin Li*, Zhijian Cao*; Sj7170, a unique dual-function peptide with a specific alpha-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. J Biol Chem . 2014, 289(17):11667-11680.

15. Wei Hong , Runhong Zhang, Zhiyong Di, Yawen He, Zhenhuan Zhao, Jun Hu, Yingliang Wu, Wenxin Li, Zhijian Cao; Design of histidine-rich peptides with enhanced bioavailability and inhibitory activity against hepatitis C virus; Biomaterials , 2013, 34(13): 3511-3522.

16.Zhijian Cao#, Yao Yu#, Yingliang Wu#, Pei Hao#, Zhiyong Di#, Yawen He#, Zongyun Chen, Weishan Yang, Zhiyong Shen, Xiaohua He, Jia Sheng, Xiaobo Xu, Bohu Pan, Jing Feng, Xiaojuan Yang, Wei Hong , Wenjuan Zhao, Zhongjie Li, Kai Huang, Tian Li, Yimeng Kong, Hui Liu, Dahe Jiang, Binyan Zhang, Jun Hu, Youtian Hu, Bin Wang, Jianliang Dai, Bifeng Yuan, Yuqi Feng, Wei Huang, Xiaojing Xing, Guoping Zhao, Xuan Li*, Yixue Li*, Wenxin Li*; The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods; Nature Communications , 2013, 4(1): 1-10.

17.Zhenhuan Zhao, Wei Hong , Zhengyang Zeng, Yingliang Wu, Kanghong Hu, Xiaohui Tian, Wenxin Li*, Zhijian Cao*; Mucroporin-M1 inhibits hepatitis B virus replication by activating the mitogen-activated protein kinase (MAPK) pathway and down-regulating HNF4alpha in vitro and in vivo; J Biol Chem , 2012, 287(36):30181-30190.