People (only the participants of GIBH are listed)
WANG Tao
Title:Principle Investigator
Subject:
Email:wang_tao@gibh.ac.cn
Address:Kaiyuan Dadao 190,510530,Guangzhou,China
Study/Work Experience

2017.03 – now

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences/ Principal Investigator

2015.04 – 2017.03

Yale University/Research Scientist

2012.06 – 2015.04

UNC-CH/Postdoctoral Associate

2010.07 – 2012.06

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences /Research Associate

2006.09 – 2010.07

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences / Ph.D

2002.09 – 2005.07

Nankai University/Master student

Research Areas

Our research focuses on the biology of aging, age-related diseases, and tissue regeneration. Previous studies have identified several distinct factors that can trigger cellular senescence, including telomere erosion, DNA damage, mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis. Cellular senescence leads to tissue dysfunction and degeneration. One of the questions we are exploring is how to enhance genome integrity. To address this, we conduct whole-genome screenings to identify new proteins or factors involved in maintaining genome integrity. Manipulating these factors may potentially delay senescence and the aging process. 

It is recognized that a decline in autophagy leads to the collapse of proteostasis, which is characterized by the accumulation of misfolded proteins. However, it remains largely unknown how upstream signaling pathways or factors contribute to the increased production of aggregated proteins during aging and senescence. Our research has revealed that tRNA methylation, specifically the m7G modification, plays a crucial role in regulating proteome homeostasis and senescence.


Academic Performance

1. Uncover the novel and unique function of vitamin C during iPS generation.

Vitamin C is one of the essential and necessary nutrient factors for human health. During Dr.Wang’s Ph.D. training he found that this natural product plays surprising roles in somatic reprogramming to facilitate iPS generation, and later on, it is demonstrated that vitamin C also improve iPS cell quality. vitamin C alleviates aberrant induction of p53 due to forced high expression of transcription factors (sox2,klf4,oct4 and c-Myc) in somatic cells during iPS generation thus it ameliorates  cell senescence to facilitate the induction of iPS generation. Now vitamin C is widely used for somatic reprogramming in worldwide.   

2. Identification of the important Histone demethylases that involved in somatic reprogramming

Histone modifications plays key roles in cell lineage commitment and maintenance through epigenetic regulation of transcription so it is expected that histone modifying enzymes may participate in iPS generation. Dr.Wang screened jumonji family proteins and found that kdm2a and kdm2b can significantly enhance somatic reprogramming efficiency, especially in the presence of vitamin C. Their results reveal a role for H3K36me and H3K9me in cell fate determination and establish a link between histone demethylases and vitamin C during induced cell fate transition.

3. Uncover a novel DNA methylation(N6mA) in mammalian Stem Cells

In Dr.Andrew.Xiao Lab at Yale University, Dr.Wang worked along with his colleagues to uncover a novel DNA methylation,N6mA, in mouse embryonic stem cell. It is well recongnized that N6mA modification widely existed in prokaryotic cell, moreover it is one of the abundant modifications in RNA molecule. Their report presented data to support that N6mA methylation also exist in DNA molecule with low abundance. The function of this novel modification is intensely investigating.

Representative Papers

1.   Fu, Y., F. Jiang, X. Zhang, Y. Pan, R. Xu, X. Liang, X. Wu, X. Li, K. Lin, R. Shi, X. Zhang, D. Ferrandon, J. Liu, D. Pei, J. Wang and T. Wang (2024). Perturbation of METTL1-mediated tRNA N(7)- methylguanosine modification induces senescence and aging. Nat Commun 15(1): 5713.

2.   Zhang, X. & Wang, T. YIPF2 regulates genome integrity. Cell Biosci 14, 114, doi:10.1186/s13578-024-01300-x (2024).

3.   Wu, T.P., T. Wang, M.G. Seetin, Y. Lai, S. Zhu, K. Lin, Y. Liu, S.D. Byrum, S.G. Mackintosh, M. Zhong, A. Tackett, G. Wang, L.S. Hon, G. Fang, J.A. Swenberg, and A.Z. Xiao. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 2016. 532:329-333. 

4.   Esteban, M.A. *, Wang, T. *, Qin, B. *, Yang, J., Qin, D., Cai, J., Li, W., Weng, Z., Chen, J., Ni, S., Chen, K., Li, Y., Liu, X., Xu, J., Zhang, S., Li, F., He, W., Labuda, K., Song, Y., Peterbauer, A., Wolbank, S., Redl, H., Zhong, M., Cai, D., Zeng, L., and Pei, D. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell, 2010. 6(1): 71-79. (*Contributed equally) 

5.   Wang, T., Chen, K., Zeng, X., Yang, J., Wu, Y., Shi, X., Qin, B., Zeng, L., Esteban, M.A., Pan, G., and Pei, D. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell, 2011. 9(6): 575-587. 

6.   Chen, J., Liu, H., Liu, J., Qi, J., Wei, B., Yang, J., Liang, H., Chen, Y., Wu, Y., Guo, L., Zhu, J., Zhao, X., Peng, T., Zhang, Y., Chen, S., Li, X., Li, D.,Wang, T., and Pei, D. H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs.Nat Genet, 2013.45(1): 34-42.

7.   Qin, D., Gan, Y., Shao, K., Wang, H., Li, W., Wang, T., He, W., Xu, J., Zhang, Y., Kou, Z., Zeng, L., Sheng, G., Esteban, M.A., Gao, S., and Pei, D. Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. J Biol Chem, 2008. 283(48): 33730-33735. 

8.   Zhang, X., Zhang, J.,Wang, T., Esteban, M.A., and Pei, D. Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells.J Biol Chem, 2008.283(51): 35825-35833.

9.   Pan, G.,Wang, T., Yao, H., and Pei, D. Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells. Bioessays, 2012.34(6): 472-476.