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Laboratory of Molecular Immunology and Cell Signaling

 
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. ​


LAB MEMBERS
LEAD 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
CURRENT PROJECTS
  • 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


PUBLICATIONS
 
 
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

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