My laboratory is devoted to the study of immunopathogenesis of infectious diseases. In recent years, our studies include dengue, histoplasmosis, SARS and tuberculosis.
We have recently developed a mouse model to study dengue hemorrhage. In this model we observed that dengue virus-infected mouse developed hemorrhage. As far as we know, this is the first time hemorrhage is induced in a mouse model. Work is in progress to identify the host effector molecule(s) as well as viral factor(s) that mediate hemorrhage.

By use of a well-characterized animal model of histoplasmosis, infection by Histoplasma capsulatum, an intracellular pathogen of the macrophage, we currently focus our study on (1) the mechanism of CD8 T cell activation involving cross-presentation of fungal antigen in mouse infected by Histoplasma; (2) the receptor molecules on mouse macropahge that are responsible for uptake of Histoplasma yeast cells; and (3) the death signaling pathway transduced in macrophage after uptake of Histoplasma yeasts.

1. Peng, J.-K., J.-S. Lin, J. T. Kung, F. D. Finkelman, and B. A. Wu-Hsieh*. 2005. The combined effect of IL-4 and IL-10 suppresses the generation of, but does not change the polarity of, type-1 T cells in Histoplasma infection.  Int. Immun. 17:193-205
2. Lin, J.-S., C.-W. Yang, D.-W. Wang and B. A. Wu-Hsieh*. 2005. Dendritic cells cross-present exogenous fungal antigens to stimulate a protective CD8 T cell response in infection by Histoplasma capsulatum. J. Immunol. 174:6282-6291
3. Lin, C.-Y., Y.-T. Ching, and B. A. Wu-Hsieh*. 2005. A computer method for ELISA spot assay analysis. Opt. Eng. 44(8):083604 1-6
4. Yen, Y.-T., F. Liao, C.-H. Hsiao, C.-L. Kao, Y.-C. Chen, and B. A. Wu-Hsieh*. 2006.  Modeling the early events of severe acute respiratory syndrome coronavirus infection in vitro.  J. Virol. 80:2684-2693
5. Hsieh, M.-F., S.-L. Lai, J.-P. Chen, J.-M. Sung, Y.-L. Lin, B. A. Wu-Hsieh, C. Geraard, A. Luster and F. Liao. 2006. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J. Immunol.177:1855-63
6. Chen, J.-P., H.-L. Lu, S.-L. Lai, G. S. Campanella, J.-M. Sung, M.-Y. Lu, B. A. Wu-Hsieh, Y.-L. Lin, T. E. Lane, A. D. Luster, and F. Liao. 2006. Dengue virus induces expression of CXC chemokine ligand 10/IFN-γ-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate. J. Immunol. 177: 3185-3192
7. Chen, H.-C., F. M. Hofman, J. T. Kung, Y.-D. Lin, and B. A. Wu-Hsieh*. 2007. Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J. Virol. 81:5518-5526
8. Yen, Y-T. Yen, Y.-D. Lin, H. –C. Chen, C.-C. Shieh and B. A. Wu-Hsieh*. 2008. Enhancement by TNF-α of dengue virus-induced endothelium production of reactive nitrogen and oxygen species is key to hemorrhage development.  J Virol. 82:12312-12324
9. Wu-Hsieh BA*, Yen YT, Chen HC. 2009. Dengue hemorrhage in a mouse model. Ann N Y Acad Sci. Sep;1171 Suppl 1:E42-7
10. J-S Lin,  J-H Huang, L-Y Hung, S-Y Wu, and B. A. Wu-Hsieh*. 2010. Distinct roles of complement receptor3, Dectin-1, and sialic acids in murine macrophage interaction with Histoplasma yeast. J Leukoc Biol. 88(1):95-106
11. Lee, H.-C., Y.-T. Yen, W.-Y. Chen, B. A. Wu-Hsieh, and S.-C. Wu*. 2011 Dengue type 4 live-attenuated vaccine viruses passaged in Vero cells affect genetic stability and dengue-induced hemorrhage in mice. PLoS One 6:e25800
12. Hsieh, S.-H., J.-S. Lin, J.-H. Huang, S.-Y. Wu, C.-L. Chu, J. T. Kung, and B. A. Wu-Hsieh*. 2011. Immunization with apoptotic phagocytes containing Histoplasma activates functional CD8+ T cells to protect against histoplasmosis. Infect. Immun. 79:4493-4502 (A featured article in “Spotlight”)
13. Hu W.-C., Y.-T. Yen, S. Singh, C.-L. Kao and B. A. Wu-Hsieh*.2012 SARS- CoV regulates immune function-related gene expression in human monocytic cells. Viral Immunology: 277-288
14. Sung J.-M., C.-K. Lee and B. A. Wu-Hsieh*. 2012. Intrahepatic Infiltrating NK and CD8 T Cells Cause Liver Cell Death in Different Phases of Dengue Virus Infection.  PloS ONE (9): e4629217
15. Sheng-Yang Wu, Jhang-Sian Yu, Fu-Tong Liu, Shi-Chuen Miaw and Betty A. Wu-Hsieh* 2013. Galectin-3 Negatively Regulate Dendritic Cell Production of IL-23/IL-17-Axis Cytokines in Infection by Histoplasma capsulatum. J Immunol. 190:3427-3437
16. Lee, Agnes Fermin, Huan-Yuan Chen, Lei Wan, Sheng-Yang Wu, Jhang-Sian Yu, Annie C. Huang, Shi-Chuen Miaw, Daniel K. Hsu, Betty A. Wu-Hsieh, and Fu-Tong Liu*. 2013. Galectin-3 modulates Th17 responses by regulating dendritic cell cytokines. Am J Pathol. 183(4):1209-22.
17. Lee, Yu-Hsiang, Chai-Lin Lai, Shih-Hung Hsieh, Chi-Chang Shieh, Li-Min Huang, and Betty A. Wu-Hsieh*. 2013. Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model. Virus Res. 26;178(2):411-22.
18. J. C. Lin, S. C. Lin, W. Y. Chen, Y. T. Yen, C. W. Lai, M. H. Tao, Y. L. Lin, S. C. Miaw and B. A. Wu-Hsieh*. 2014. Dengue viral protease interaction with NF-kappaB inhibitor alpha/beta results in endothelial cell apoptosis and hemorrhage development. J Immunol. 193(3): 1258-1267.