Academic Profile

Academic Profile

Assoc Prof Su I-Hsin

Associate Professor, School of Biological Sciences

Email: ihsu@ntu.edu.sg
Assoc Prof Su I-Hsin

Biography
Dr. Su earned her B.A. degree from National Taiwan University, then moved to Germany for her graduate studies, where she received a ‘Diplom’ in Biology and a Ph.D. in Immunology from the Institute for Genetics, University of Cologne. Following graduate school, she successfully completed her postdoctoral studies at The Rockefeller University, New York, USA, before relocating to Singapore to establish her own research group. She is currently a tenured Associate Professor at the School of Biological Sciences, Nanyang Technological University. Here, she maintains a research group of 5-8 people by means of competitive grant awards and have authored several highly-cited, peer-reviewed papers published in high-impact journals including Cell, Nature Immunology, Stem Cell, Genes & Development, the Journal of Experimental Medicine, and the Journal of Clinical Investigation. Her laboratory is interested in elucidating the molecular mechanisms leading to the functional regulation of immune cells and cancers. She also frequently serves as a reviewer for several international research journals and grant agencies.
Research Interests
In the biological system, most of the important cellular events, such as growth, survival, apoptosis, differentiation and migration are regulated by post-translational modifications. Aside from phosphorylation, protein methylation has emerged over the last decade as one of the major control mechanisms in protein function. Notably, arginine methylation has been implicated in several key cytosolic and nuclear processes, including receptor signaling, protein transport and gene transcription and may represent the most common type of protein methylation in mammalian cells. In contrast, relatively few lysine-methylated proteins have been identified and those that have been characterized are associated with transcriptional regulation. The functional implications of lysine methylation of cytosolic proteins remain largely unclear.

Previously, we suggested a cytosolic role for the histone lysine methyltransferase (HKMT), Ezh2, in regulating lymphocyte activation (Su et al., Cell 2005, 121, 425-436). Our recent data further demonstrate that Ezh2 regulates adhesion dynamics and migration of leukocytes through direct methylation of the extra-nuclear protein, talin. Ezh2-mediated methylation of talin, a key regulatory molecule in cell migration, disrupts talin binding to F-actin and thereby promotes adhesion structure turnover (Gunawan et al., Nature Immunology 2015, 16: 505-516).

The physiological significance of this novel finding in leukocytes is further supported by two follow-up studies. The important role of cytosolic Ezh2 in governing Langerhans cell migration and tolerogenic dermal dendritic cell-mediated host protection against cutaneous allergy (Loh et al., iScience 2018,10: 23–39). Furthermore, the endogenous Ezh2-mediated talin methylation is demonstrated to be critical for neutrophil infiltration during peritonitis, suggesting a critical role of talin methylation in microbe induced sepsis (J Immunol 2018, 201: 3651-3661).

Interestingly, a significant role for cytoplasmic Ezh2 in neoplastic transformation is further demonstrated in a study led by Drs. Nandini Venkatesan & Jong Fu Wong. They have shown that disruption of Ezh2’s cytosolic function is sufficient to abolish Ezh2’s transforming capacity and cytoplasmic Ezh2 enriched cells are likely to represent a group of aggressive cancer stem cells (Oncogene 2018, 37: 461-477).

It is possible that Ezh2 and other lysine methyltransferases (KMTs) mediate the methylation of additional proteins to modulate various cytosolic signaling events. We have also identified several uncharacterized cytoplasmic KMTs that may be involved in regulating immune responses. Collectively, our studies aim to elucidate lysine-methylation-regulated signaling networks controlling various cellular functions in immune cells and cancers.
Current Projects
  • CY2002 CN Yang Scholars Programme Undergraduate Research Experience
  • Ezh2-regulated dendritic cell functions in health and disease
  • Function and physiological significance of Setd3 in immune responses
  • Functional Signifiance of the Ezh2-Vav1 Interaction in normal & tumor cells
  • Functional implication of cytoplasmic EZH2 in cancer stem cells
  • Functional significance of talin methylation in normal and tumor cells
  • Molecular characterization of UBR7-regulated cell adhesion and migration
  • The Role of Cytosolic Ezh2 in prostate cancer
  • The role of Polycomb Group Protein Ezh2 in immune Response of Dendritic cells
  • Transcriptional Regulation of Ezh2 Expression in Immune Cells and Lymphoma
  • Understanding mammalian microRNA biology in health and disease
Selected Publications
  • Thomas Lim Jun Feng, Maegan Bunjamin, Christiane Ruedl, Su I-Hsin. (2020). Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling. The Journal of Experimental Medicine, .
  • Lim, T.J.F. and I., Su. (2018). Talin1 Methylation Is Required for Neutrophil Infiltration and Lipopolysaccharide-Induced Lethality. Journal of Immunology, 201(12), 3651-3661.
  • Lim, T. J. F., and Su, I. H. (2018). Neutrophil Infiltration and Lipopolysaccharide-Induced Lethality.. Journal of Immunology, 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.
  • Evrard, M., Kwok, I. W. H., Chong, S. Z., Teng, K. W. W., Becht, E., Chen, J. M., Sieow, J. L., Penny, H. L., Ching, G. C., Devi, S., Adrover, J. P. M., Li, J. L. Y., Liong, K. H., Tan, L., Poon, Z., Foo, S., Chua, J. W., Su, I. H., Balabanian, K., Bachelerie, F., Biswas, S. K., Larbi, A., Hwang, W. Y. K., Madan, V., Koeffler, H. P., Wong, S. C., Newell, E. W., Hidalgo, A., Ginhoux, F., and Ng, L. G. (2018). Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions.. Immunity, 48, 364-379.

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