Lab of Regenerative Medicine and Neural Repair
Jian ZhaoAssociate Professor , PhD, Associate Professor
School of Life Science and Technology, Shanghai Institute for Advanced Immunochemical Institute
- 1992/09-1996/07, Fudan University, Shanghai, China, B.S.
- 1996/09-1999/07, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, M.S.
- 2000/10-2004/01, The Ruperto-Carola University of Heidelberg, Germany, Ph.D.
- 1996/07-2000/09, Young Scientists Group, Max-Planck Guest Laboratory, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Assistant Research Professor
- 2000/10-2004/01, German Cancer Research Center, Heidelberg, Germany, PhD candidate, Research assistant
- 2004/02-2007/01, German Cancer Research Center, Heidelberg, Germany, Post Doctoral Fellow, Scientist
- 2007/02-2016/02, Lab of Cell Signaling, Institute of Biochemistry and cell biology, Shanghai Institutes for Biology Sciences (SIBS), Chinese Academy of Sciences (CAS), Associate Professor
- 2015/06-2018/07, Stem cell core facility, Shanghai East Hospital, Tongji University School of Medicine , Director
- 2016/03-2018/04, Institute for Advanced Study, Tongji University, Shanghai, China, Professor
- 2018/05-2019/02, School of Medicine, Tongji University, Shanghai, China, Professor
- 2019/03-Present, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), School of Life Science and Technology, ShanghaiTech University, Shanghai, Associate Professor
New Mechanisms, New Drug Targets and New Therapeutic Strategies against Dementia Translational Research
In more than a decade of research, I have focused on the study of new mechanisms of important signal transduction pathways in cell fate determination as well as in the pathogenesis and progression of neurodegenerative diseases. Our major findings include:
1. Established a novel chemical-induced transdifferentiation technology, providing induced human neural (progenitor) cells for disease-modeling. A series of in vitro small molecule transdifferentiation induction systems were established, and the possible general formula of transdifferentiation was proposed, by which exploration of the regulatory mechanisms of neurodegenerative diseases with human cells become possible.
2. Elucidated that the secretase protein complex as the key regulators of the development and progression of the Alzheimer’s diseases, providing a unique path for finding novel drugs that affects Aβ production and metabolism by various signal transduction proteins or protein complexes on the cell surface. We found that cell surface receptors, secretases and their regulatory proteins form functional secretase protein complexes (holo-secretase complex). Our results show that assembly of these secretase complex mediates the production of pathogenic β-amyloid, whereas intervention of which retards the generation of β-amyloid and Alzheimer's disease process. Our studies not only reveal new regulatory molecules in AD pathogenesis but propose new therapeutic strategies against the disease.
Our efforts will continue to focus on elucidating new mechanisms of key signal transduction pathways mediating the pathogenesis and progression of neurodegenerative diseases based on our previous achievements.
Direction I. Generating induced human neural (progenitor) cells as disease-modeling system.
Direction II. Cellular surface protein complexes as novel targets for the Alzheimer's disease.
Direction III. Exploring the multiple etiological characteristics of neurodegenerative diseases and new strategies for systematic treatment with multiple targets
Representative Publications (*First Author, # Corresponding Author)
- 1. Hu, Wenxiang*; Qiu, Binlong; Guan, Wuqiang; Wang, Qinying; Wang, Min; Li, Wei; Gao, Longfei; Shen, Lu; Huang, Yin; Xie, Gangcai; Zhao, Hanzhi; Jin, Ying; Tang, Beisha; Yu, Yongchun; Zhao, Jian#; Pei, Gang#.Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules.CELL STEM CELL. 2015. 17(2):204-212.
- 2. Cheng, Lin*; Gao, Longfei; Guan, Wuqiang; Mao, Jianxin; Hu, Wenxiang; Qiu, Binlong; Zhao, Jian#; Yu, Yongchun; Pei, Gang#.Direct conversion of astrocytes into neuronal cells by drug cocktail.CELL RESEARCH. 2015. 25(11):1269-1272.
- 3. Cui, Jin*; Wang, Xiaoyin; Li, Xiaohang; Wang, Xin; Zhang, Chenlu; Li, Wei; Zhang, Yangming; Gu, Haifeng; Xie, Xin; Nan, Fajun#; Zhao, Jian#; Pei, Gang#.Targeting the gamma-/beta-secretase interaction reduces beta-amyloid generation and ameliorates Alzheimer's disease-related pathogenesis.CELL DISCOVERY. 2015. 1.
- 4. Mao, Jianxin*; Huang, Shichao; Liu, Shangfeng; Feng, Xiao-Lin; Yu, Miao; Liu, Junjun; Sun, Yi Eve; Chen, Guoliang; Yu, Yang; Zhao, Jian#; Pei, Gang#.A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.AGING CELL. 2015. 14(5):784-796.
- 5. Wang, Xin*; Cui, Jin; Li, Wei; Zeng, Xianglu; Zhao, Jian#; Pei, Gang#.gamma-Secretase Modulators and Inhibitors Induce Different Conformational Changes of Presenilin 1 Revealed by FLIM and FRET.JOURNAL OF ALZHEIMERS DISEASE. 2015. 47(4):927-937.
- 6. Cheng, Lin*; Hu, Wenxiang; Qiu, Binlong; Zhao, Jian#; Yu, Yongchun; Guan, Wuqiang; Wang, Min; Yang, Wuzhou; Pei, Gang#.Generation of neural progenitor cells by chemical cocktails and hypoxia.CELL RESEARCH. 2014. 24(6):665-679.
- 7. Hou, Yujun*; Wang, Ying; Zhao, Jian#; Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang#.Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits.PLOS ONE. 2014. 9(11).
- 8. Hu, Wenxiang*; Zhao, Jian; Pei, Gang#.Activation of Aryl Hydrocarbon Receptor (AhR) by Tranilast, an Anti-allergy Drug, Promotes miR-302 Expression and Cell Reprogramming.JOURNAL OF BIOLOGICAL CHEMISTRY. 2013. 288(32):22972-22984.
- 9. Liu, Xiaosong*; Zhao, Xiaohui; Zeng, Xianglu; Bossers, Koen; Swaab, Dick F.; Zhao, Jian#; Pei, Gang#.beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology.CELL RESEARCH. 2013. 23(3):351-365.
- 10. Zhao, Jian#*; Pei, Gang.Arrestins in Metabolic Regulation.MOLECULAR BIOLOGY OF ARRESTINS. 2013. 118:413-427.
- 11. Zhao, Jian#*; Pei, Gang#.Why Cell Reprogramming is Functionally Linked to Aging?.AGING-US. 2011. 3(8):700-700.