Research Field

Brain injury and aging are major causes of cognitive decline and functional impairment, yet effective strategies for restoring brain function remain limited. Functional reconstruction of the central nervous system relies on coordinated repair processes at the cellular and circuit levels, among which myelin regeneration plays a critical but often underappreciated role. Myelin, the multilayered membrane structure that ensheathes neuronal axons, is essential for maintaining neuronal integrity and enabling rapid signal conduction. Emerging evidence indicates that myelin dysfunction contributes not only to classical demyelinating disorders but also to brain aging and a broad spectrum of neurological diseases. Therefore, understanding the mechanisms governing myelin regeneration is of fundamental importance for promoting functional recovery following brain injury and aging.

Our research focuses on the role of myelin in brain function, specifically investigating the regulatory mechanisms underlying myelin development, formation, and regeneration, as well as the contribution of myelin to aging, neurodegenerative diseases, and other brain disorders, alongside the development of new therapeutics. Utilizing techniques in stem cell biology, chemical biology, and high-throughput chemical screening, we aim to develop small-molecule compounds that promote myelination, decipher the key signaling pathways that govern myelin development and regeneration, and investigate the role of myelin in maintaining neuronal function and facilitating repair following injury.

Our goal is to explore new strategies for ameliorating cognitive dysfunction and delaying aging through targeted remyelination, thereby providing novel approaches and technological support for chemical intervention and endogenous repair in neurological disorders. Our original research has been published in journals such as Cell Stem Cell, Cell Reports, Nucleic Acids Research, and Journal of Molecular Cell Biology. Our work is supported by grants including the National Key R & D Program of China, the National Natural Science Foundation of China, the Basic Research Program of Shanghai Science and Technology Committee, and the Project of the Shanghai Municipal Education Commission.

We are always looking for highly motivated researchers and students with a strong interest in stem cells and brain function. Postdoctoral positions are currently available. Candidates who have recently obtained a Ph.D., particularly those with expertise in stem cell biology, molecular biology, or animal models, are strongly encouraged to apply. Applicants could contact mingliang.zhang@shsmu.edu.cn. We look forward to hearing from you.

Personal Introduction

Dr. Mingliang Zhang, Principal Investigator and Ph.D. Supervisor, is a recipient of the Shanghai Eastern Talent Program, Shanghai Pujiang Talent Program and Distinguished Professor of the Shanghai Eastern Scholar Program. He received his Bachelor’s degree from Xiamen University in 2002, and PhD from Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in 2009. From 2010 to 2016, he worked as a postdoc at the Scripps Research Institute and the J. David Gladstone Institutes. He joined the Department of Histoembryology and Genetic Development, Shanghai Jiao Tong University School of Medicine since 2016. He currently serves as a member of the Glial Cell Branch of the Chinese Society for Neuroscience, the Committee on Basic Research and Clinical Translation of the Chinese Medical Doctor Association, the Neural Repair and Regeneration Committee of the China Association for Pharmaceutical Biotechnology, the Standing Expert Committee of the Cell Medicine Branch of the China Food and Drug Enterprise Quality and Safety Promotion Association, and the Youth Working Committee of the Chinese Society for Cell Biology.

Scientific Research Projects

• The National Key R & D Program of China

• The National Natural Science Foundation of China

• The Basic Research Program of Shanghai Science and Technology Committee,

• The Project of the Shanghai Municipal Education Commission

Publications

1. Li Yawen, et al. Combination Therapy Dramatically Promotes Remyelination. J Mol Cell Biol. 2025, 17(3), mjaf005.

2. Yang Yudong, et al. Small-molecule activators specific to adenine base editors through blocking the canonical TGF-β pathway. Nucleic Acids Res. 2022 Sep 23;50(17):9632-9646.

3. Wang Jia, et al. Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions. Nat Biomed Eng. 2022 Apr;6(4):403-420.

4. Zhang GuanYu, et al. Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells. J Mol Cell Biol. 2022 Feb 24;14(1):mjab076.

5. Cheng Zhouli, et al. The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming. Cell Rep. 2020 Jul 14;32(2):107877.

6. Sun Pingxin, et al. Maintenance of Primary Hepatocyte Functions In Vitro by Inhibiting Mechanical Tension-Induced YAP Activation. Cell Rep. 2019 Dec 3;29(10):3212-3222.e4.

7. Liu Chang, et al. Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach. J Mol Cell Biol. 2019 Jun 1;11(6):489-495.

8. Zhang Mingliang, et al. Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation. Cell Stem Cell. 2016 May 5;18(5):653-67.

9. Cao Nan, et al. Conversion of human fibroblasts into functional cardiomyocytes by small molecules. Science. 2016 Jun 3;352(6290):1216-20.

10. Zhu Saiyong, et al. Human pancreatic beta-like cells converted from fibroblasts. Nat Commun. 2016 Jan 6;7:10080.

11. Xie Fei, et al. Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells. Stem Cells Dev. 2016 Aug 15;25(16):1243-8.

12. Zhu Saiyong, et al. Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells. Cell Res. 2014 Jan;24(1):126-9.

13. Xu Tao, et al. Concise review: chemical approaches for modulating lineage-specific stem cells and progenitors. Stem Cells Transl Med. 2013 May;2(5):355-61.

14. Tong Xiajing, et al. Est1 protects telomeres and inhibits subtelomeric y'-element recombination. Mol Cell Biol. 2011 Mar;31(6):1263-74.

15. Zhang Mingliang, et al. Yeast telomerase subunit Est1p has guanine quadruplex-promoting activity that is required for telomere elongation. Nat Struct Mol Biol. 2010 Feb;17(2):202-9.

16. Liao Xinhua, et al. Characterization of recombinant Saccharomyces cerevisiae telomerase core enzyme purified from yeast. Biochem J. 2005 Aug 15;390(Pt 1):169-76.

17. Zhang Mingliang, et al. Chemical Approaches to Controlling Cell Fate. in Principles of Developmental Genetics, 2nd Edition, Moody S., 2014, Academic Press. pp59-76.

Patent

• Zhang Mingliang, and Ding Sheng. Chemical reprogramming to generate neuronal cells， PCT/US2016/045290, WO/2017/027280

• Zhang Mingliang, and Yang Yudong. Compounds and chemical modulation methods for specifically promoting activity of adenine base editor, and uses thereof. 202210266569.7, PCT/CN2022/115597