Principal Investigator, Associate Professor
Lab of Regenerative Medicine and Neural Repair
Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology (SLST), ShanghaiTech University
Research Area: Regenerative Medicine and Neural Repair
Regenerative medicine holds great potential bringing new knowledge and treatments to medicine. It will take efforts and resources to figure out the proper ways of using stem cells and revolutionizing our treatment of many debilitating diseases and injuries. Right now, we are still learning how to generate and grow stem cells, understand and control how stem cells differentiate to become specific cell types-heart, neuron, skin, liver, or whatever kind is needed.
Neurodegenerative diseases cause heavy burden both to family and society. Till now there is no effective prevention or disease-modifying therapy available. Elucidate neuronal dysfunction and molecular mechanisms of these neurodegenerative disorders should pave the way to the discovery of new drugs or effective treatment against the diseases. In our previous work, we uncovered that the GPCR/secretase complex regulates the specificity of secretase for A production which suggests that intervention of either formation or trafficking of the GPCR/secretase complex could lead to a new strategy against AD potentially with fewer side effects. We found several active components in traditional medicines with clinically proved effects enhanced the NPC proliferation under physiological and pathological conditions in which growth factor supply was deficient. We further established transdifferentiation systems to generate human iPSCs, NPCs or neuronal cells from somatic cells by lineage-specific transcription factors or chemical cocktails. We systematically generated iPSC, iNPC and iN from about 100 patients suffered from AD, PD, depression, anxiety disorder and etc., providing human disease-modeling cells to explore the pathogenesis as well as novel therapeutic strategies thereof.
1. Wenxiang Hu, Binlong Qiu, Wuqiang Guan, Qinying Wang, Min Wang, Wei Li, Longfei Gao, Lu Shen, Yin Huang, Gangcai Xie, Hanzhi Zhao, Ying Jin, Beisha Tang, Yongchun Yu, Jian Zhao* and Gang Pei*. Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. (2015) Cell Stem Cell. 17:204-12. [*Co-corresponding authors]
2. Lin Cheng, Longfei Gao, Wuqiang Guan, Jianxin Mao, Wenxiang Hu, Binlong Qiu, Jian Zhao, Yongchun Yu and Gang Pei. Direct conversion of astrocytes into neuronal cells by drug cocktail (2015) Cell Res. 25:1269–1272.
3. Jin Cui, Xiaoyin Wang, Xiaohang Li, Xin Wang, Chenlu Zhang, Wei Li, Yangming Zhang, Haifeng Gu, Xin Xie, Fajun Nan, Jian Zhao* and Gang Pei*. Targeting the γ-/β-secretase interaction reduces β-amyloid generation and ameliorates Alzheimer’s disease-related pathogenesis. (2015) Cell Discovery 1:15021. [Co-corresponding authorship and Co-first authorship]
4. Jianxin Mao, Shichao Huang, Shangfeng Liu, Xiao-Lin Feng, Miao Yu, Junjun Liu, Yi Eve Sun, Guoliang Chen, Yang Yu, Jian Zhao* and Gang Pei1*. A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation. (2015) Aging Cell. 14(5):784-96 [*Co-corresponding authors]
5. Xin Wang, Jin Cui, Wei Li, Xianglu Zeng, Jian Zhao* and Gang Pei*. γ-secretase modulators and inhibitors induce different conformational changes of presenilin 1 revealed by FLIM and FRET. (2015) Journal of Alzheimer’s Disease 47:927-37 [*Co-corresponding authors]
6. Lin Cheng, Wenxiang Hu, Binlong Qiu, Jian Zhao*, Yongchun Yu, Wuqiang Guan, Min Wang, Wuzhou Yang and Gang Pei*. Generation of neural progenitor cells by chemical cocktails and hypoxia. (2014) Cell Res. 24:665-7 [Co-corresponding authorship and Co-first authorship]
7. Yujun Hou, Ying Wang, Jian Zhao*, Xiaohang Li, Jin Cui, Jianqing Ding, Ying Wang, Xianglu Zeng, Yun Ling, Xiaoheng Shen, Shengdi Chen, Chenggang Huang and Gang Pei*. Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits (2014) PLoS ONE (2014), 9(11):e111215. [Co-corresponding authorship and Co-first authorship]
8. Wenxiang Hu, Jian Zhao* and Gang Pei*. Activation of aryl hydrocarbon receptor by Tranilast, an anti-allergy drug, promotes miR-302 expression and cell reprogramming. (2013) J Biol Chem. 288: 22973-84 [*Co-corresponding authors]
9. Xiaosong Liu, Xiaohui Zhao, Xianglu Zeng, Koen Bossers, Dick F. Swaab, Jian Zhao* and Gang Pei*. β-Arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology. (2013) Cell Res., 23: 351-65. [*Co-corresponding authors]
10. Jian Zhao and Gang Pei. Arrestins in metabolic regulation. (2013) Prog Mol Biol Transl Sci. 118:413-27. (Review)
11. Xiaosong Liu and Jian Zhao. GPCR, a rider of Alzheimer’s disease. (2011) Frontiers in Biol. 6: 282-288. (Review)
12. Jian Zhao and Gang Pei. Why Cell Reprogramming is Functionally Linked to Aging? (2011) Aging, 3(8) (Review)