Directory

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

Selected:

Tan, J.Y.J, Anderson, D.E., Rathore, A.P.S., O’Neill, A., Mantri, C.K., Saron, W.A.A., Lee, C.Q.E., Chu, W.C., Kang, A.E.Z., Foo, R., Kalimuddin, S., Low, J.G., Ho, L., Tambyah, P., Burke, T.W., Woods, C.W., Chan, K.R., Karhausen, J., St. John, A.L. (2023). Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19. Journal of Clinical Investigation. Oct 2;133(19):e149834.  doi: 10.1172/JCI149834.

St. John, A. L., Rathore, A.P.S., Ginhoux, F. (2022) New perspectives on the origins and heterogeneity of mast cells. Nature reviews immunology. an;23(1):55-68.  doi: 10.1038/s41577-022-00731-2. Epub 2022 May 24.

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.S., St. John, A.L. (2020) Cross-reactive immunity among flaviviruses Frontiers in Immunology. 11,334.

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

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

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.*, 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 

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