The St. John lab research program focuses on understanding host immune responses to virulent pathogens:

• Innate and adaptive immune responses to dengue: Dengue is a mosquito-borne virus infection. We use immune competent mouse models to identify the ways the host immune system responds to dengue infection.

• Mast cell responses to viral pathogens: Mast cells are best known for their involvement in conditions such as asthma, allergy and anaphylaxis, however, they also can provide immune surveillance for viral pathogens such as dengue virus. We are learning that MC responses to different viruses are highly unique. Several projects in the lab focus on understanding how mast cells contribute to immune protection and pathology during viral infection.

• Flavivirus-induced vascular pathology: Many flaviviral pathogens induce immune pathology involving vascular and/or blood brain barrier leakage. We are particularly interested in the role of mast cell derived proteases in inducing vascular permeability or blood brain barrier permeability.

• Vertical transmission of Zika virus infection: Zika virus is able to cross the placenta from mother to developing fetus. Members of our lab are investigating the mechanisms of vertical transmission of infection with emphasis on understanding how components of the immune system influence fetal infection.

• Developing novel vaccination strategies, diagnostics, and therapeutics for infectious diseases: Highly host-adapted pathogens require specialized vaccine strategies for effective immune protection. We apply the knowledge gained in our basic research studies to develop novel vaccine strategies. We are also translating our findings that mast cell stabilizing drugs can limit dengue severity in animal models by working with collaborators at multiple institutions in Singapore to test whether mast cell stabilizing drugs can limit vascular leakage in dengue patients. 

Visit the St. John Lab here

Msallam, R.*, Balla, J.*, Rathore, A.P.S., Kared, H, Malleret, B., Saron, W.A.A., Liu, Z., Hang, J.W., Dutertre, C.A., Larbi, A., Chan, K.Y.J., St. John, A.L.**, Ginhoux, F.** (2020) Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE. Science. doi: 10.1126/science.aba0864

St. John, A.L. and Rathore, A.P.S. (2020) Early Insights into Immune Responses during COVID-19. Journal of Immunology doi: 10.4049/jimmunol.2000526

Rathore, A.P., Mantri, C.K., Aman, S.A., Syenina, A., Ooi, J., Jagaraj, C.J., Goh, C.C., Tissera, H., Wilder-Smith, A., Ng, L.G., Gubler, D.J. & St John, A.L.* Dengue virus-elicited tryptase induces endothelial permeability and shock. Journal of Clinical Investigation 130 (2019). doi: 10.1172/JCI128426

Rathore, A.P.S., Saron, W.A.A., Lim, T., Jahan, N. and St. John, A.L. (2019) Maternal immunity and antibodies to dengue promote infection and Zika virus-induced microcephaly in fetuses. Science Advances. doi: 10.1126/sciadv.aav3208

Masri, M.F.B., Mantri, C.K.M., Rathore, A.P.S., St. John, A.L. (2019) Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT2 receptors. Blood . doi: 10.1182/blood-2018-08-869156

Hsieh, J., Rathore, A.P.S., Soundarajan, G., St. John, A.L. (2019). Japanese encephalitis virus neuropenetrance is driven by mast cell chymase. Nature Communications.10, Article number: 706 doi: 10.1038/s41467-019-08641-z

St. John, A.L., and Rathore, A.P.S. (2019). Adaptive immune responses to primary and secondary dengue virus infections. Nature Reviews Immunology. doi:10.1038/s41577-019-0123-x 

Mantri CK, St. John AL (2018) Immune synapses between mast cells and γδ T cells limit viral infection. Journal of Clinical Investigation. doi: 10.1172/JCI122530

Arifuzzaman A, Ang WXG, Choi HW, Nilles ML, St. John AL, and Abraham SN. (2018) Necroptosis of infiltrated macrophages drives Yersinia pestis dispersal within buboes. JCI Insight. doi: 10.1172/jci.insight.122188 

Rathore APS, St. John AL. (2018) Immune responses to dengue virus in the skin. Open Biology. 8: 180087. doi: 10.1098/rsob.180087 

Saron, W.A.A., Rathore, A.P.S., Ting, L., Ooi, E.E., Low, J., Abraham, S.N., and St. John, A.L. Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells. Science Advances. 4 (2018). doi: 10.1126/sciadv.aar4297

Malavige, G.N., Wijewickrama, A., Fernando, S., Jeewandara, C., Ginneliya, A., Samarasekara, S., Madushanka, P., Punchihewa, C., Paranavitane, S., Idampitiya, D., Wanigatunga, C., Dissanayake, H. Prathapan, S., Gomes, L., Aman, S.A.B., St. John, A.L, & Ogg, G.S. (2018) A preliminary study on efficacy of rupatadine for the treatment of acute dengue infection. Scientific Reports. doi: 10.1038/s41598-018-22285-x 

Tissera, H., Rathore, A.P.S., Leong, W.Y., Pike, B.L., Warkentien, T.E., Farouk, F.S., Syenina, A., Ooi, E.E., Gubler, D.J., Wilder-Smith, A., St. John, A.L. (2017) Chymase is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients. Journal of Infectious Diseases. doi: 10.1093/infdis/jix447 

Morrison, J., Rathore, A.P.S., Mantri, C.K., Aman, S.A.B, Nishida, A. and St. John, A.L. (2017) Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model. Journal of Virology . doi: 10.1128/JVI.00617-17 

Chan, KR, Wang, X, Saron, WAA, Gan, ES, Tan, HC, Mok, DZL, Zhang, SLX, Lee, Yie Hou, Liang, C, Wijaya, L, Ghosh, S, Cheung, YB, Tannenbaum, SR, Abraham, SN, St. John, AL, Low, JGH, Ooi, EE. (2016) Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity. Nature Microbiology. 1, 16164, doi:10.1038/nmicrobiol.2016.164 

Goh KC, Tang CK, Norton DC, Gan ES, Tan HC, Sun B, Syenina A, Yousuf A, Ong XM, Kamaraj US, Cheung YB, Gubler DJ, Davidson A, St John AL, Sessions OM, Ooi EE. (2016) Molecular determinants of plaque size as an indicator of dengue virus attenuation. Scientific Reports. May 17;6:26100. doi: 10.1038/srep26100 

Gómez, J.M.M., O, L.C., Lam, J.H., Aman, S.A.B., Libau, E.A., Lee, P.X., St. John, A.L., Alonso, S. (2016). Maternal antibody-mediated disease enhancement in type I interferon-deficient mice leads to lethal disease associated with liver damage. PLoS Neglected Tropical Diseases. Mar 23; 10(3):e0004536. doi:10.1371/journal.pntd.0004536 

Li, J.L., Lim, C.H., Tay, F.W., Goh, C.C., Devi, S., Malleret, B., Lee, B., Bakocevic, N., Chong, S.Z., Evrard, M., Tanizaki, H., Lim, H.Y., Russell, B., Renia, L., Zolezzi, F., Poidinger, M., Angeli, V., St. John, A.L., Harris, J.E., Tey, H.L., Tan, S.M., Kabashima, K., Weninger, W., Larbi, A., Ng, L.G. (2015) Neutrophils Self-Regulate Immune Complex-Mediated Cutaneous Inflammation Through CXCL2. Journal of Investigative Dermatology. doi: 10.1038/JID.2015.410 

Syenina, A., Jagaraj, C.J., Aman, S.A., Sridharan, A. and St John, A.L. (2015) Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcγ receptors. eLife. Mar 18;4. doi: 10.7554/eLife.05291 

St. John, A.L., Ang, W.X.G., Huang, M.N., Kunder, C.A., Chan, E.W., Gunn, M.D., Abraham, S.N. (2014) S1P-dependent trafficking of intracellular Yersinia pestis through lymph nodes establishes bubos and systemic infection. Immunity. Sep 18;41(3):440-50. doi: 10.1016/j.immuni.2014.07.013 

Gubler, D. J. & St. John, A. L., “Dengue Viruses” in Reference Module in Biomedical Sciences (Elsevier, 2014). (book chapter) 

St. John, A.L. (2013). Influence of Mast Cells on Dengue Protective Immunity and Immune Pathology. PLoS Pathogens. 9(12): e1003783. doi:0.1371/journal.ppat.1003783

St. John, A.L., Abraham, S. N., and Gubler, D. J. (2013). Barriers to Pre-Clinical Investigations of Anti-Dengue Immunity and Immune-pathology. Nature Reviews Microbiology. Jun;11(6):420-6. doi: 10.1038/nrmicro3030 

St. John, A.L.*, Rathore, A. P. S., Raghavan, B., Ng, M. L., and Abraham, S. N. (2013). Contributions of Mast Cells and Vasoactive Products, Leukotrienes and Chymase, to Dengue Virus-Induced Vascular Leakage. eLife. Apr 30;2:e00481. (Featured article with commentary) doi: 10.7554/eLife.00481 

St. John, A.L.*, and Abraham, S. N. (2013). Innate Immunity and its Regulation by Mast Cells. Journal of Immunology. May 1;190(9):4458-63. doi:10.4049/jimmunol.1203420 

Chan, C.Y., St John, A.L., & Abraham, S.N., (2013). Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38 (2), 349-359. doi:10.1016/j.immuni.2012.10.019 

St John, A.L.*, Chan, C.Y., Staats, H.F., Leong, K.W. & Abraham, S.N. (2012). Synthetic Mast Cell Granules as Adjuvants to Promote and Polarize Immunity in Lymph Nodes. Nature Materials 11 (3), 250-257. (Featured in “News and Views”) doi: 10.1038/nmat3222 

Kunder, C.A., St John, A.L.* & Abraham, S.N. (2011). Mast cell modulation of the vascular and lymphatic endothelium. Blood . 118 (20), 5383-5393. doi: 10.1182/blood-2011-07-358432 

Chan, C.Y., St John, A.L., & Abraham, S.N. (2011). Plasticity in mast cell responses during bacterial infections. Current Opinion in Microbiology 15 (1), 78-84. doi:10.1016/j.mib.2011.10.007 

St John, A.L.*, Rathore, A., Yap, H., Metcalfe, D., Ng, M.M., Vasudevan, S. and Abraham, S.N. (2011). Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance. Proceedings of the National Academy of Sciences U S A. 108 (22), 9190-9195 (2011). doi:10.1073/pnas.1105079108 

Abraham, S.N. and St John, A.L. (2010). Mast cell-orchestrated immunity to pathogens. Nature Reviews Immunology 10(6):440-452. doi: 10.1038/nri2782 

St John, A.L., and Abraham, S.N. (2009). Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines. Nature Medicine 15, 1259-1265. doi: 10.1038/nm.2036 

Kunder*, C.A., St John*, A.L., Li, G., Leong, K.W., Berwin, B., Staats, H.F., and Abraham, S.N. (2009). Mast cell-derived particles deliver peripheral signals to remote lymph nodes. Journal of Experimental Medicine 206, 2455-2467. doi: 10.1084/jem.20090805 

Shelburne, C.P., Nakano, H., St John, A.L., Chan, C., McLachlan, J.B., Gunn, M.D., Staats, H.F., and Abraham, S.N. (2009). Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues. Cell Host & Microbe 6, 331-342. 

Dzhagalov, I., St John, A. , and He, Y.W. (2007). The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages. Blood 109, 1620-1626.