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Location: Home >> Faculty >> Developmental Biology

Developmental Biology

Shilai Bao

Education
Ph.D. Molecular Biology, University of Sciences and Technology of China(USTC), China. 1999
M.S. Molecular Biology, University of Sciences and Technology of China(USTC), China. 1993
B.S. Tea Sciences, Anhui Agricultural College, Anhui, Hefei, P.R.China. 1988

PROFESSIONAL EXPERIENCE:
2006-present:Professor, Institute of Genetics and Developmental Biology, CAS. 2003-2005:Associate Professor, Institute of Genetics and Developmental Biology, CAS.
1999-2003:Postdoctoral Fellow, MD Anderson Cancer Center.
1999:Visiting Scholar, Purdue University.
1990-1999: Lecturer and Graduate Student in Biology Department, USTC.

RESEARCH INTEREST:
Golgi Apparatus Biogenesis The Golgi apparatus (GA) plays a central role in the post-translational modification, sorting, and transport of proteins. Maintenance of GA structure and function depends on Golgi matrix proteins. The function of GA in development and disease pathogenesis, however, remains largely unknown. My laboratory is interested in elucidating the molecular mechanism of PRMT5 complex components in regulating GA structure and function. Our previous studies find that PRMT5 localizes to GA and physically interacts with golgin GM130. Both PRMT5 and GM130 methylation are critical for Golgi structure. We are generating knockout mice to investigate into the significance of the Golgi apparatus in development and disease pathogenesis.

Epigenetics Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing nearly one third of all pediatric cancers. The ALL is caused by the defects of differentiation processes from hematopietic stem cell to mature lymphocytes. Many proteins have been found to be involved in lymphocytes differentiation and ALL pathogenesis. We are interested in revealing the effects of PRMT5 and PRMT7, two enzymes catalyze histone H4R3 symmetric dimethylation, and other histone modifications in regulating the lymphocyte differentiation and the ALL pathogenesis.

Epigenetics We also take advantage of arabidopsis, a model plant has a large of T-DNA insertion mutants, to study the “histone code” of flowering time controlling.

KEY PUBLICATIONS::（* corresponding author）

1. He H, Chen J, Zhao J, Zhang P, Qiao Y, Wan H, Wang J, Mei M, Bao S*, Li Q*. (2021) PRMT7 targets of Foxm1 controls alveolar myofibroblast proliferation and differentiation during alveologenesis. Cell Death & Disease DOI:10.1038/s41419-021-04129-1.

2. Pang Q, Liu C, Qiao Y, Zhao J, Lam SM, Mei M, Shui G, Bao S*, Li Q*. (2021) GM130 regulates pulmonary surfactant protein secretion in alveolar type II cells. Sci China Life Sci. doi: 10.1007/s11427-020-1875-x.

3. Lam S, Zhang C, Wang Z, Ni Z, Zhang S, Yang S, Huang X, Mo L, Li J, Lee B, Mei M, Huang L, Shi M, Xu Z, Meng F, Cao W, Zhou M, Shi L, Chua G, Li B, Cao J, Wang J, Bao S, Wang Y, Song J？, Zhang？ F, Wang F, Shui G. (2021) A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19. Nature Metabolism 3:909-922.

4. Chen M, Dong F, Chen M, Shen Z, Wu H, Cen C, Cui X, Bao S, Gao F. (2021) PRMT5 regulates ovarian follicle development by facilitating Wt1 translation. Elife 10:e68930. doi: 10.7554/eLife.68930. Online ahead of print.

5. Li F, Dong C, Yang T, Bao S, Fang W, Lucas W, Zhang Z. (2021) The tea plant CsLHT1 and CsLHT6 transporters take up amino acids, as a nitrogen source, from the soil of organic tea plantations. Horticulture Research 8:

6. Yang T, Xie Y, Lu X, Yan X, Wang Y, Ma J, Cheng X, Lin S, Bao S, Wan X, Lucas W, Zhang Z. (2021) Shading Promoted Theanine Biosynthesis in the Roots and Allocation in the Shoots of the Tea Plant (Camellia sinensis L.) Cultivar Shuchazao. J. Agric. Food Chem. 69(16): 4795–4803.

7. Chen M, Wang Y, Lin L, Dong F, Wu H, Bao S, Gao F. (2020) PRMT7 is involved in regulation of germ cell proliferation during embryonic stage. Biochem Biophys Res Commun. 533(4):938-944.

8. Dong C, Li F, Yang T, Feng L, Zhang S, Li F, Li W, Xu G, Bao S, Wan X, Lucas WJ, Zhang Z. (2020) Theanine transporters identified in tea plants (Camellia sinensis L.). Plant J. 101(1):57-70.2019.

9. Li F, Li H, Dong C, Yang T, Zhang S, Bao S, Wan X, Zhang Z. (2020) Theanine transporters are involved in nitrogen deficiency response in tea plant (Camellia sinensis L.). Plant Signal Behav. 15(3):1728109.

10. Jin H, Du Z, Zhang Y, Antal J, Xia Z, Wang Y, Gao Y, Zhao X, Han X, Cheng Y, Shen Q, Zhang K, Elder RE, Benko Z, Fenyvuesvolgyi C, Li G, Rebello D, Li J, Bao S, Zhao RY, Wang D. (2020) A distinct class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. Sci Adv. 6(20):eaba3418.

11. Mei M, Zhang R, Zhou Z, Ying Z, Wang J, Zhang H, Zheng H*, Bao S*. (2019) PRMT5-mediated H4R3sme2 Confers Cell Differentiation in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia. Clin. Cancer Res. 25(8): 2633-2643.

12. Ding X, Jiang X, Tian R, Zhao P, Li L, Wang X, Chen S, Zhu Y, Mei M, Bao S, Liu W, Tang Z, Sun Q. (2019) RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells. Autophagy. 15(10):1774-1786.

13. Li Q*, Jiao J, Li H Wan H, Zheng C, Cai J, Bao S*. (2018) Histone arginine methylation by Prmt5 is required for lung branching morphogenesis through repression of BMP signaling. J Cell Sci. 131(14): jcs217406.（Cover story）

14. Xu L, Zhang H, Mei M, Du C, Huang X, Li J, Wang Y, Bao S*, Zheng H*. (2018) Phosphorylation of serine/arginine-rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia. Cancer Sci. 109(12):3805-3815.

15. Jiang Q, Lu X, Huang P, Gao C, Zhao X, Xing T, Li G, Bao S, Zheng H. (2018) Expression of miR-652-3p and Effect on Apoptosis and Drug Sensitivity in Pediatric Acute Lymphoblastic Leukemia. Biomed Res Int. 2018:5724686.

16. Hu J, Yang H, Mu J, Lu T, Peng J, Deng X, Kong Z, Bao S, Cao X, Zuo J. (2017) Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants. Molecular Cell 67:1-9.

17. Liu C, Mei M, Li Q, Roboti P, Pang Q, Ying Z, Gao F, Lowe M*, Bao S*. (2017) Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice. Proc Natl Acad Sci U S A. 114(2):346-351.（Cover story）

18. Han F, Liu C, Zhang L, Chen M, Zhou Y, Qin Y, Wang Y, Chen M, Duo S, Cui X, Bao S, Gao F*. (2017) Globozoospermia and lack of acrosome formation in GM130-deficient mice. Cell Death & Disease 8: e2532

19. Li Q, Zhao Y, Yue M, Xue Y, Bao S*.（2016）The Protein Arginine Methylase 5 (PRMT5/SKB1) Gene Is Required for the Maintenance of Root Stem Cells in Response to DNA Damage. J Genet Genomics 43(4):187-97.（Cover story）

20. Ying Z, Mei M, Zhang P, Liu C, He H, Gao F, Bao S*. (2015) Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription. The Journal of Immunology 195(4):1538-1547.

21. Zhang H, Cheng H, Wang Q, Zeng X, Chen Y, Yan J, Sun Y, Zhao X, Li W, Gao C, Gong W, Li B, Zhang R, Nan L, Wu Y, Bao S*, Han J,* & Zheng H*. (2015) An advanced fragment analysisbased individualized subtype classification of pediatric acute lymphoblastic leukemia. Sci Rep. 5:12435

22. Wang Y, Zhu T, Li Q, Liu C, Han F, Chen M, Zhang L, Cui X, Qin Y, Bao S*, Gao F*. (2015) Prmt5 is required for germ cell survival during spermatogenesis in mice. Sci Rep. 5:11031

23. Wang Y, Li Q, Liu C, Han F, Chen M, Zhang L, Cui X, Qin Y, Bao S, Gao F (2015) Protein Arginine Methyltransferase 5 (Prmt5) Is Required for Germ Cell Survival During Mouse Embryonic Development. Biol Reprod.114:127308.

24. Li Q, Li Y, Gu B, Fang L, Zhou P, Bao S, Huang L, Dai X. (2015) Akt Phosphorylates Wnt Coactivator and Chromatin Effector Pygo2 at Serine 48 to Antagonize Its Ubiquitin/Proteasome-mediated Degradation. J Biol Chem. 290(35):21553-67.

25. Zhang H, Zhu L, He H, Zhu S, Zhang W, Liu X, Zhao X, Gao C, Mei M, Bao S *, Zheng H*. (2014) NF-kappa B mediated Up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia. Molecular Cancer 13(5).

26. Fan H, Zhang Z, Wang N, Cui Y, Sun H, Liu Y, Wu H, Zheng S, Bao S*, Ling H* (2014) SKB1/PRMT5-mediated histone H4R3 dimethylation of Ib subgroup bHLH genes negatively regulates iron homeostasis in arabidopsis thaliana. Plant Journal 77(2):209-221.

27. Yue M, Li Q, Zhang Y, Zhao Y, Zhang Z, Bao S*. (2013) Histone H4R3 methylation catalyzed by SKB1/PRMT5 is required for maintaining shoot apical meristem . PLoS One 8(12):.

28. Liu X, Zou L, Zhu L, Zhang H, Du C, Li Z, Gao C, Zhao X, Bao S, Zheng H. (2012) miRNA mediated up-regulation of cochaperone p23 acts as an anti-apoptotic factor in childhood acute lymphoblastic leukemia. Leuk Res. 36(9):1098-104.

29. Zou L, Zhang H, Du C, Liu X, Zhu S, Zhang W, Li Z, Gao C, Zhao X, Mei M, Bao S, Zheng H. (2012) Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia. J Hematol Oncol. 27;5:42.

30. Sun, L., Wang, M., Lv, Z., Yang, N., Liu, Y., Bao, S., Gong, W., and Xu, R. (2011) Structural Insights into Protein Arginine Symmetric Dimethylation by PRMT5. PNAS 108(51): 20538-20543.

31. Zhang, Z., Zhang, S., Zhang, Y., Wang, X., Li, D., Li, Q., Yue, M., Li, Q., Zhang, Y.E., Xu, Y., Xue, Y., Chong, K., and Bao, S*. (2011). Arabidopsis Floral Initiator SKB1 Confers High Salt Tolerance by Regulating Transcription and Pre-mRNA Splicing through Altering Histone H4R3 and Small Nuclear Ribonucleoprotein LSM4 Methylation. Plant Cell 23 (1):396-411.

32. Guo S, and Bao S*. (2010) srGAP2 arginine methylation regulates cell migration and cell spreading through promoting of dimerization. J Biol Chem 285: 35133-41.

33. Jiang Y, Wang X, Bao S, Guo R, Johnson D, Shen X, Li L. (2010) The INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. PNAS 107(40):17274-9.

34. Zhou, Z*., Sun, X*., Zou, Z., Sun, L., Zhang, T., Guo, S., Wen, Y., Liu, L., Wang, Y., Qin, J., Li, L., Gong, W., and Bao, S*. (2010) PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130. Cell Research 20, 1023-33.

35. Ren, J., Wang, Y., Liang, Y., Zhang, Y., Bao, S. and Xu, Z. (2010). Methylation of ribosomal protein s10 by protein arginine methyltransferase 5 regulates ribosome biogenesis. J Biol Chem. 285, 12695-12705.

36. Li, Z, Zhang, W., Wu, M., Zhu, S., Gao, C., Sun, L., Zhang, R., Qiao, N., Xue, H., Hu, Y., Bao, S*, Zheng, H*. and Han, J.D*. (2009) Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia. Blood, 114, 4486-4493.

37. Liu, R., Strom, A. L., Zhai, J., Gal, J., Bao, S., Gong, W., and Zhu, H. (2009). Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase. Int J Biochem Cell Biol 41, 1371-1380.

38. Sun L, Zhou Z, Xie X, and Bao S*. (2008) Study on biological activity of various truncations of human PRMT5 in E.coli. Progress in Biochemistry and Biophysics 35 (7).

39. Wang, X., Zhang, Y., Ma, Q., Zhang, Z., Xue, Y., Bao, S*., and Chong, K*. (2007). SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis. EMBO J. 26, 1934-1941.

40. Hou, X., Wang, Y., Zhou, Z., Bao, S., Lin, Y., and Gong, W. (2007). Crystal structure of SAM-dependent O-methyltransferase from pathogenic bacterium Leptospira interrogans. J Struct Biol 159, 523-528.

41. Liu, Z., Zhou, Z., Chen, G., and Bao, S*. (2007). A putative transcriptional elongation factor hIws1 is essential for mammalian cell proliferation. Biochem Biophys Res Commun 353, 47-53.

42. Wang, X., Xu, Y., Han, Y., Bao, S., Du, J., Yuan, M., Xu, Z., and Chong, K. (2006). Overexpression of RAN1 in rice and Arabidopsis alters primordial meristem, mitotic progress, and sensitivity to auxin. Plant Physiol 140, 91-101.

43. Wang, X., Zou, L., Lu, T., Bao, S., Hurov, K. E., Hittelman, W. N., Elledge, S. J., and Li, L. (2006). Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 23, 331-341.

44. Cheng, Z., Bao, S., Shan, X., Xu, H., and Gong, W. (2006). Human thioesterase superfamily member 2 (hTHEM2) is co-localized with beta-tubulin onto the microtubule. Biochem Biophys Res Commun 350, 850-853.

45. Bao, S., Lu, T., Wang, X., Zheng, H., Wang, L. E., Wei, Q., Hittelman, W. N., and Li, L. (2004). Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene 23, 5586-5593.

46. Hu, M. C., Lee, D. F., Xia, W., Golfman, L. S., Ou-Yang, F., Yang, J. Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004). IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225-237.

47. Bao, S., Qyang, Y., Yang, P., Kim, H., Du, H., Bartholomeusz, G., Henkel, J., Pimental, R., Verde, F., and Marcus, S. (2001). The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast Schizosaccharomyces pombe. J Biol Chem 276, 14549-14552.

48. Kim, H. W., Yang, P., Qyang, Y., Lai, H., Du, H., Henkel, J. S., Kumar, K., Bao, S., Liu, M., and Marcus, S. (2001). Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1. Mol Cell 7, 1095-1101.

49. Li, H., Sherman, D. M., Bao, S., and Sherman, L. A. (2001). Pattern of cyanophycin accumulation in nitrogen-fixing and non-nitrogen-fixing cyanobacteria. Arch Microbiol 176, 9-18.