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Tongbiao ZHAO, Ph. D.

stem cell and immunology


Co-workers: Jiani Cao, Xiaoyan Li, Haifeng Gu, Qian Zhao, Chao Zhang, Kun Liu, Pinglei Liu, Hongyan Sun, Jianxia Zhou, Linyuan Jin, Jiaqi Gong, Haoyu Xu, Shenghui Chen

• ZHAO Group website

 

  Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, human ESCs hold great promise for cell replacement therapy. However, one major obstacle is that the cells derived from human ESCs have allogeneic antigens when transplanted into the patients, leading to immune rejection even under chronic immune suppression that itself poses serious risk for cancer and infection. Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells. Whereas it has been generally assumed that these autologous cells should be immune-tolerated by the recipient from whom the iPSCs are derived, our recent work showed that cells derived from iPSCs can trigger immune rejection response. The findings suggest appropriate immune tolerance induction should be reconsidered for clinic development of pluripotent stem cells. Like development, somatic cell reprogramming is an epigenomic reconstruction process. How does the transcription factors orchestrate the process is one of the most critical open questions. Our long-term goal is to understand the epigenetic mechanisms of reprogramming and differentiation.



An episomal approach to generate mouse and human iPSCs

 

 

Plain english:
  Our research interests mainly focus on stem cells and immunology including: 1) Understanding the immunogenicity of induced pluripotent stem cells; 2) Developing new tolerance strategies to derivatives of stem cells; 3) Dissecting the epigenetic mechanisms of reprogramming.

 

Selected publications:

• 1. Zhao T1, Zhang Z1, Westenskow P1, Todorova D, Hu Z, Lin T, Rong Z, Kim J, He J, Wang M, Clegg D, Yang Y, Zhang K, Friedlander M, Xu Y*.2015 Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells. Cell Stem Cell, 17, 353-359.

• 2. Wang L, Cao J, Wang Y, Lan T, Liu L, Wang W, Jin N, Gong J, Zhang C, Teng F, Yan G, Li C, Li J, Wan H, Hu B, Li W, Zhao X, Qi Z*,Zhao T*,Zhou Q* . 2015 Immunogenicity and functional evaluation of iPSC-derived organs for trans-plantation. Cell Discovery, 1, 15015.

• 3. Zhao T, Zhang Z, Rong Z, Xu Y*. 2011 Immunogenicity of induced pluripotent stem cells. Nature, 474(7350), 212-216. 
Highlighted by Nature (Nature 474:165); Nature Medicine (Nature Medicine 17: 670)
Recommended by Faculty of 1000 (F1000.com/11136956)
Reported by Nature, Scinece, New York Time, New Scientist, ScineceDaily, UK Guardian, USA today et al.

• 4. Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs S, Xu Y*. 2010 Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc Natl Acad Sci USA. 107(30), 13312-13317.

• 5. Zhao T, Xu Y*. 2010 p53 and stem cells: new developments and new concerns.Trends Cell Biol, 20(3), 170-175

• 6. Zhao T, Zhang H, Guo Y, Zhang Q, Lu H, Hou Q, Hua G, Fan Z*. 2007 Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of the target cells. Cell Death Differ, 14, 489-499.

• 7. Zhao T1, Zhang H1, Guo Y, Fan Z*. 2007 Granzyme K directly processes Bid to release of cytochrome c and endonuclease G leading to mitochondrial - dependent cell death.  J Biol Chem, 16, 12104-12111.