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RESEARCH

Immunology    Microbiology

Lymphocyte Differentiation

Our lab is interested in investigating the intricate transcriptional network in the activation, terminal differentiation as well as exhaustion in T and B lymphocytes. Our genes of interest include BLIMP1 and RUNX1 associated with differentiation of T cell into cytokine-secreting helper T, and B cell into antibody-secreting plasma cell. We aim to elucidate the importance of these genes in the pathogenesis of autoimmune diseases and immune cell malignancies e.g. multiple sclerosis and myeloma. 

Published works

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  1. Wong WF*, Kohu K, Nagashima T, Funayama R, Matsumoto M, Movahed E, Tan GM, Yeow TC, Looi CY, Kurokawa M, Osato M, Igarashi K, Nakayama K, and Satake M (2015). The artificial loss of Runx1 reduces the expression of quiescence-associated transcription factors in CD4(+) T lymphocytes. Molecular Immunology 68, 223-233. 

  2. Wong WF*, Looi CY, Kon S, Movahed E, Funaki T, Chang LY, Satake M, and Kohu K (2014). T-cell receptor signaling induces proximal Runx1 transactivation via a calcineurin-NFAT pathway. European Journal of Immunology 44, 894-904. 

  3. Looi CY, Sasahara Y, Watanabe Y, Satoh M, Hakozaki I, Uchiyama M, Wong WF, Du W, Uchiyama T, Kumaki S, Tsuchiya S, and Kure S (2014). The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells. International Immunology 26, 341-352.

  4. Kon S, Minegishi N, Tanabe K, Watanabe T, Funaki T, Wong WF, Sakamoto D, Higuchi Y, Kiyonari H, Asano K, Iwakura Y, Fukumoto M, Osato M, Sanada M, Ogawa S, Nakamura T, and Satake M (2013). Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. Journal of Clinical Investigation 123, 1123-1137.

  5. Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, and Satake M (2012). Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. Journal of Immunology 188, 5408-5420. 

  6. Wong WF, Kurokawa M, Satake M, and Kohu K (2011). Down-regulation of Runx1 expression by TCR signal involves an autoregulatory mechanism and contributes to IL-2 production. Journal of Biological Chemistry 286, 11110-11118. 

  7. Wong WF, Kohu K, Chiba T, Sato T, and Satake M (2011). Interplay of transcription factors in T-cell differentiation and function: the role of Runx. Immunology 132, 157-164. 

  8. Wong WF, Nakazato M, Watanabe T, Kohu K, Ogata T, Yoshida N, Sotomaru Y, Ito M, Araki K, Telfer J, Fukumoto M, Suzuki D, Sato T, Hozumi K, Habu S, and Satake M (2010). Over-expression of Runx1 transcription factor impairs the development of thymocytes from the double-negative to double-positive stages. Immunology 130, 243-253. 

  9. Kohu K, Ohmori H, Wong WF, Onda D, Wakoh T, Kon S, Yamashita M, Nakayama T, Kubo M, and Satake M (2009). The Runx3 transcription factor augments Th1 and down-modulates Th2 phenotypes by interacting with and attenuating GATA3. Journal of Immunology 183, 7817-7824.

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Chlamydia trachomatis

Genital chlamydial infection is one of the most common sexually transmitted bacterial infections worldwide. It causes vaginitis, cervicitis, urethritis, endometriosis, and is associated with severe sequelae including pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility in women. We are currently investigating various aspects of Chlamydia-induced pathogenesis including its virulence factors which induce inflammatory responses and metabolic changes in the host cells. Our works aim at providing insights into a rational design of a subunit vaccine for prevention of chlamydial infection.

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Published works

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  1. Cheok YY, Lee CYQ, Cheong HC, Looi CY, Wong WF* (2020). Chronic Inflammatory Diseases at Secondary Sites Ensuing Urogenital or Pulmonary Chlamydia Infections. Microorganisms 8(1). pii: E127. 

  2. Cheong HC, Yap PSX, Chong CW, Cheok YY, Lee CYQ, Tan GMY, Sulaiman S, Hassan J, Sabet NS, Looi CY, Gupta R, Arulanandam B, AbuBakar S, Teh CSJ, Chang LY, and Wong WF* (2019). Diversity of endocervical microbiota associated with genital Chlamydia trachomatis infection and infertility among women visiting obstetrics and gynecology clinics in Malaysia. PLoS One 14, e0224658. 

  3. Cheong HC, Lee CYQ, Cheok YY, Tan GMY, Looi CY, and Wong WF* (2019). Chlamydiaceae: Diseases in Primary Hosts and Zoonosis. Microorganisms 7. 

  4. Cheong HC, Lee CYQ, Cheok YY, Shankar EM, Sabet NS, Tan GMY, Movahed E, Yeow TC, Sulaiman S, Wong WF*, Looi CY, Gupta R, Hassan J, Arulanandam B, and AbuBakar S (2019). CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients. Immunobiology 224, 34-41. 

  5. Wong WF, Chambers JP, Gupta R, and Arulanandam BP (2019). Chlamydia and Its Many Ways of Escaping the Host Immune System. Journal of Pathogen 2019, 8604958.

  6. Yeow TC, Wong WF*, Sabet NS, Sulaiman S, Shahhosseini F, Tan GM, Movahed E, Looi CY, Shankar EM, Gupta R, Arulanandam BP, Hassan J, and Abu Bakar S (2016). Prevalence of plasmid-bearing and plasmid-free Chlamydia trachomatis infection among women who visited obstetrics and gynecology clinics in Malaysia. BMC Microbiology 16, 45. 

  7. Tan GM, Lim HJ, Yeow TC, Movahed E, Looi CY, Gupta R, Arulanandam BP, Abu Bakar S, Sabet NS, Chang LY, and Wong WF* (2016). Temporal proteomic profiling of Chlamydia trachomatis-infected HeLa-229 human cervical epithelial cells. Proteomics 16, 1347-1360. 

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Helicobacter pylori

Well-known for its association with gastritis and gastric cancer, our lab is investigating different interactions of bacteria with innate receptors on human macrophages. We have identified a receptor Podoplanin that is highly upregulated and plays a crucial role in directing macrophage migration during H. pylori infection. Our works aim at limiting chronic inflammation by targeting molecules essential for immune cells recruitment and activation in H. pylori infected individuals.

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Published works

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  1. Cheok YY, Tan GMY, Lee CYQ, Abdullah S, Looi CY and Wong WF* (2022). Innate Immunity Crosstalk with Helicobacter pylori: Pattern Recognition Receptors and Cellular Responses. International Journal of Molecular Sciences 23:7561. PDF

  2. Cheok YY, Tan GMY, Fernandez KC, Chan YT, Lee CYQ, Cheong HC, Looi CY, Vadivelu J, Abdullah S, Wong WF* (2021). Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection. Frontiers in Immunology 12:702156. 

  3. Cheok YY, Lee CYQ, Cheong HC, Vadivelu J, Looi CY,​ Abdullah S and Wong WF* (2021). An Overview of Helicobacter pylori Survival Tactics in the Hostile Human Stomach Environmen. Microorganisms. 8(1). pii: E127.

  4. Tan GM, Looi CY, Fernandez KC, Vadivelu J, Loke MF, and Wong WF* (2015). Suppression of cell division-associated genes by Helicobacter pylori attenuates proliferation of RAW264.7 monocytic macrophage cells. Scientific Reports 5, 11046. 

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HIV & immune exhaustion

Few other ongoing works include HIV & HIV associated pathogens i.e. Candida/Cryptococcus. Advancement in HAART has significantly extended life-span of people living with HIV, however, viral persistence in the host trigger issues such as T cell exhaustion and reactivation of latent infection. Our research focus on the association between cellular metabolic programming and T cell activities. 

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Published works

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  1. Saeidi A, Zandi K, Cheok YY, Saeidi H, Wong WF*, Lee CYQ, Cheong HC, Yong YK, Larsson M, and Shankar EM (2018). T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses. Frontiers in Immunology 9, 2569.

  2. Chong PP, Chin VK, Wong WF, Madhavan P, Yong VC, and Looi CY (2018). Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance-An Update. Genes 9. 

  3. Movahed E, Cheok YY, Tan GMY, Lee CYQ, Cheong HC, Velayuthan RD, Tay ST, Chong PP, Wong WF*, and Looi CY (2018). Lung-infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection. BMC Immunology 19, 32. 

  4. Movahed E, Tan GM, Munusamy K, Yeow TC, Tay ST, Wong WF*, and Looi CY (2016). Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans. Frontiers in Microbiology 7, 360. 

  5. Movahed E, Munusamy K, Tan GM, Looi CY, Tay ST, and Wong WF* (2015). Genome-Wide Transcription Study of Cryptococcus neoformans H99 Clinical Strain versus Environmental Strains. PLoS One 10, e0137457. 

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Sponsoring Grants

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