DESCRIPTION OF RESEARCH WORK

In the biological system, most of the important cellular events, such as growth, differentiation and migration are regulated by post-translational modifications. Protein methylation has emerged as one of the major control mechanisms in protein function. Earlier, we suggested a cytosolic role for the histone lysine methyltransferase, Ezh2, in regulating lymphocyte activation (Cell 2005, 121, 425-436). Our recent data reveal that Ezh2-mediated methylation of talin1, a key regulatory molecule in cell migration, disrupts its binding to F-actin and thereby promotes adhesion turnover and cell migration (Nature Immunology 2015, 16: 505-516). The physiological significance of cytoplasmic Ezh2 is further substantiated by studies in leukocytes (iScience 2018,10: 23–39; J Immunol 2018, 201: 3651-3661) and in neoplastic transformation (Oncogene 2018, 37: 461-477). Ezh2 and other lysine methyltransferases are likely to methylate additional proteins to modulate various cytosolic signaling events. ​

 

I-hsin SuLEAD PI
Su​ I-Hsin
Associate Professor

Email: ihsu@ntu.edu.sg
Phone: (65) 6513 8687​
Office: SBS-02N-46
Thomas Lim Jun Feng
Research Fellow

Email: thomasjf.lim@ntu.edu.sg
Maegan Bunjamin
Research Associate

Email: mbunjamin@ntu.edu.sg
Daniel Law Cheng Lui
Project Officer

Email: daniel.law@ntu.edu.sg
Nethaji Thangaraj
Project Officer

Email: nethaji.thangaraj@ntu.edu.sg
Hanisah MK
Project Officer/Masters Student

Email: hanisah.mk@ntu.edu.sg
Alice Sint Thida Bo
PhD Student

Email: sint0003@e.ntu.edu.sg
Lam Nai Yao
FYP-URECA student

Email: LAMN0004@e.ntu.edu.sg

 

  • To determine the physiological significance of uncharacterized cytoplasmic lysine methyltransferases (KMTs) in immune cells (Tier 2, July 2018- June 2021)
  • Biochemical and functional studies of uncharacterized cytosolic KMTs (Tier 2, July 2018- June 2021; Tier 1, Feb 2018- Jan 2021)
  • To identify cytoplasmic determinants for cellular transformation (NMRC-OFIRG, Mar 2019-Feb 2023)
  • The role of Ezh2-regulated thymic dendritic cells in T cell development

Full list of publications can be found here​
  • Su, I. H., Basavaraj, A., Krutchinsky, A. N., Hobert, O., Ullrich, A., Chait, B. T., and Tarakhovsky, A. (2003) Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nature Immunology 4, 124-131
  • Su, I., Dobenecker, M. W., Dickinson, E., Oser, M., Basavaraj, A., Marqueron, R., Viale, A., Reinberg, D., Wulfing, C., and Tarakhovsky, A. (2005) Polycomb group protein Ezh2 controls actin polymerization and cell signaling. Cell 121, 425-436
  • Ezhkova, E., Pasolli, H. A., Parker, J. S., Stokes, N., Su, I. H., Hannon, G., Tarakhovsky, A., and Fuchs, E. (2009) Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells. Cell 136, 1122-1135
  • Neo, W. H., Yap, K., Lee, S. H., Looi, L. S., Khandelia, P., Neo, S. X., Makeyev, E. V., and Su, I. H. (2014) MicroRNA miR-124 Controls the Choice between Neuronal and Astrocyte Differentiation by Fine-tuning Ezh2 Expression. Journal of Biological Chemistry 289, 20788-20801
  • Neo, W. H., Lim, J. F., Grumont, R., Gerondakis, S., and Su, I. H. (2014) c-Rel Regulates Ezh2 Expression in Activated Lymphocytes and Malignant Lymphoid Cells. Journal of Biological Chemistry 289, 31693-31707
  • Gunawan, M., Venkatesan, N., Loh, J. T., Wong, J. F., Berger, H., Neo, W. H., Li, L. Y. J., La Win, M. K., Yau, Y. H., Guo, T., See, P. C. E., Yamazaki, S., Chin, K. C., Gingras, A. R., Shochat, S. G., Ng, L. G., Sze, S. K., Ginhoux, F., and Su, I. H. (2015) The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin. Nature Immunology 16, 505-516
  • Lim, T. J. F., and Su, I. H. (2018) Talin1 Methylation Is Required for Neutrophil Infiltration and LipopolysaccharideInduced Lethality. J Immunol 201, 3651-3661
  • Loh, J. T., Lim, T. J. F., Ikumi, K., Matoba, T., Janela, B., Gunawan, M., Toyama, T., Bunjamin, M., Ng, L. G., Poidinger, M., Morita, A., Ginhoux, F., Yamazaki, S., Lam, K. P., and Su, I. H. (2018) Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells. iScience 10, 23-39
  • Venkatesan, N., Wong, J. F., Tan, K. P., Chung, H. H., Yau, Y. H., Cukuroglu, E., Allahverdi, A., Nordenskiold, L., Goke, J., Geifman-Shochat, S., Lin, V. C. L., Madhusudhan, M. S., and Su, I. H. (2018) EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms. Oncogene 37, 461-477
  • Lim, T. J. F., Bunjamin, M., Ruedl, C., Su, I. H.Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling (2020) J. Exp. Med. 217, doi.org/10.1084/jem.20191810