Dr. Fang Liao, Assistant Professor
Institute of Biomedical Sciences, Academia Sinica
1980, B.S.¡@ Fu-Jen Catholic University
1982, B.S.¡@ National Taiwan University
1992, Ph.D.¡@Johns Hopkins University School of Medicine, USA
1992 - 1996¡@Postdoctoral fellow
¡@¡@¡@¡@¡@¡@ National Institute of Health
1996 - 1999¡@Research Associate
¡@¡@¡@¡@¡@¡@ National Institute of Health
¡@My research focuses on understanding the chemokines and their receptors on the basis of biochemistry and immunology. I have two principal research interests: (1) the study of the structure-function and signal transduction in a CC chemokine receptor-CCR6; (2) the study of the function of chemokines and their receptors in the immune-regulated diseases and viral diseases.
¡@Chemokines are a family of small, secreted, and inducible proteins. The best-described activities for chemokines are as chemotactic factors for leukocytes. Chemokines are increasingly recognized to have diverse effects on the physiology of lymphocytes, including the accumulation of lymphocytes at inflammatory sites, the polarization of lymphocytes and the localization of lymphocytes in lymphoid tissues. Chemokines target cells through members of the seven transmembrane domain G protein-coupled receptor superfamily.
¡@In my previous work I cloned the CC chemokine receptor-CCR6, identified its ligand as CCL20/MIP-3, and characterized CCR6 expression and function on leukocytes. CCR6 is predominately expressed in lymphoid tissue, and in peripheral blood lymphocytes, including memory T cells, B cells, and dendritic cells. The CCR6 ligand, CCL20/MIP-3 is expressed in a range of cells in response to inflammatory stimuli. CCR6 and CCL20/MIP-3 are likely important for positioning and recruiting cells for the initiation of memory immune responses. The major interests of my laboratory on CCR6 research are studying (1) the structure-function relationship of CCR6 using both site-directed mutagenesis and domain swapping approaches, and (2) the signal transduction of CCR6 using proteomics-based technologies.
¡@Another major objective of my research is to study the biology of chemokines/chemokine receptors in inflammatory and infectious diseases using gene-targeted mice. The projects includes (1) study the mechanism by which IL-15 receptor signaling regulates chemokine expression in inflammatory diseases; (2) study the biological functions of chemokines/chemokine receptors on dengue virus infection.
1. Hsieh, M-F., Chen, J-P., Lai, S-L., Sung, J-M., Wu-Hsieh, B., Lin, Y-L., Gerald, C, Luster, A. and Liao, F. Both CXCR3 and CXCL10/IP-10 are required for resistance to primary dengue virus infection. J. Immunol. (under revision)
2. Chen, J-P, Liao, N-S., Lai, S-L, Hsu, L, Mao, W-Y. Ku, M-C, and Liao, F. 2005. Reduced 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity response in IL-15 receptor alpha-deficient mice correlates with diminished CCL5/RANTES and CXCL10/IP-10 expression. Eur. J. Immunol. 35, 690.
3. Ai, L., Lee, S. -F., Chen, S. S.-L. and Liao, F. 2004. Molecular characterization of CCR6: involvement of multiple domains in ligand binding and receptor signaling. J. Biomed. Sci. 11, 818.
4. Fang, L.-W., Tai, T. ¡VS., Yu, W.-N, Liao, F. and Lai, M.-Z. 2004. Phosphatidylinositide 3-kinase priming couples c-FLIP to T cell activation. J Biol. Chem. 279, 13.
5. Ai, L. and Liao, F. 2002. Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling. Biochemistry 41, 8332.
6. Liao, F., Shirakawa, A.K., Foley, J.F., Rabin, R.L. and Farber, J.M. 2002. Human B cells become highly responsive to MIP-3ƒÑƒ}CCL20 after cellular activation without changes in CCR6 expression or ligand binding. J. Immunol. 168, 4871.
7. Park, M. K., Amichay, D., Love, P., Wick, E., Liao, F., Grinberg, A., Rabin, R. L., Zhang, H.W., Gebeyehu, S., Wright, T., Iwasaki, A., Weng, Y., DeMartino, J., Elkins, K., and Farber, J. M. 2002. The CXC Chemokine Murine Mig (CXCL9) Is Made by Antigen Presenting Cells, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo. J. Immunol. 169, 1433.
8. Liao, F., Rabin, R.L., Smith, C.S., Sharma, G. and Farber, J.M. 1999. CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 J. Immunol. 162, 186.
9. Rabin, R.L., Park, M.K., Liao, F., Swofford, R., Stephany, D., Farber, J.M. 1999. T cell subset-specific responses of chemokine receptors are achieved through regulation of both receptor expression and signaling. J. Immunol.162, 3840.
10. Sullivan, S.K., McGrath, D.A., Liao, F., Boehme, S.A., Farber, J. M. and Bacon, K. B. 1999. MIP-3ƒÑ induceds human esoinophil migration and activation of the mitogen-activated protein kinases. J. Leukoc. Biol. 66, 674.
11. Gasperini, S., Marchi, M., Calzetti, F., Laudanna, C., Vicentini, L., Olsen, H., Murphy, M., Liao, F., Farber, J. and Cassatella, M.A.1999. Gene expression and production of the monokine induced by IFN-gamma(MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10(IP-10) chemokines by human neutrophils. J. Immunol. 162, 4928.
12. Horton, M.R., McKee, C.M., Bao, C., Liao, F., Farber, J.M., Hodge-DuFour J, Pure, E., Oliver, B.L., Wright, T.M., and Noble, P.W. 1998. Hyaluronan fragments synergize with interferon-gamma to induce the CXC chemokines Mig and interferon-inducible protein-10 in mouse macrophages. J. Biol. Chem. 273, 35088.
13. Kanegane, C., Sgadarei, C., Kanegane, H., Teruya-Feldstein, J., Yao, L., Gupta, G., Farber, J.M., Liao, F., Liu, L. and Tosato, G. 1998. Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12. J. Leukoc. Biol. 64, 384.
14. Coughlin, C.M., Salhany, K.E., Gee, M.S., LaTemple, D. C., Kotenko, S., Ma, X.J., Giorgia, G., Wysocka, M., Kim, J.E., Liu, L., Liao, F., Farber, J.M., Pestka, S., Trinchieri, G. and Lee, W.M F.1998. Tumor cell responses to IFN affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9, 25.
15. Alkhatib, G, Liao, F., Berger, E.A., Farber, J.M. and Peden, K.W.C. 1997. A new SIV co-receptor, STRL33. Nature 388, 238.
16. Liao, F. Anderson, R., Su, J., Ullrich, J., Kreider, B. R. and Farber, J. M. 1997. STRL22 is a receptor for the CC chemokine MIP-3ƒÑƒ|ƒnBiochem. Biophys. Res. Comm.236, 212.
17. Liao, F.,Alkhatib, G., Peden, K. W. C.,Sharma, G.,Berger, E. A.and Farber, J. M. 1997. STRL33, a novel chemokine receptor-like protein, function as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med. 185, 2015.
18. Schwartz, G. N., Liao, F., Szabo, J. M., Gress, R. E., and Farber, J. M. 1997. Mig chemokine suppressed insulin like growth factor II(IGF-II) dependent stimulatory effects on proliferation and production of committed and primitive hematopoietic progenitors from CD34+ bone marrow cells. J. Immunol.159, 895.
19. Liao, F., Lee, H-H., and Farber, J. M. 1997. Cloning of STRL22, new human gene encoding a G protein-coupled receptor related to chemokine receptors and located on chromosome 6q27. Genomics 40,175.
20. Sgadari, C., Farber, J. M., Angiolillo, A. L., Liao, F., Teruya-Feldstein, J., Burd, P. R., Yao, L., Gupta, G., Kanegane, C., and, Tosato, G. 1997. Mig, the monokine induced by interferon-ƒ×, promotes tumor necrosis in vivo. Blood 89, 2635.
21. Liao, F., Rabin, R., Yannelli, J., Koniaris, L., Vanguri, P., and J. M. Farber. 1995. Biochemical and functional characterization of the Mig chemokine. J. Exp. Med. 182, 1301.
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