Division of Rheumatology & Immunology
The Zhang laboratory research currently focuses on the following areas:
The molecular mechanisms behind Fli-1’s impact on autoimmune disease development. Fli-1 is a member of the Ets family of transcription factors and is highly expressed in hematopoietic lineages, including endothelial cells and T and B cells. Two-fold overexpression of the Fli-1 protein in transgenic mice results in the development of a lupus-like disease. Expression of Fli-1 in systemic lupus erythematosus (lupus) patients and animal models of lupus is higher compared to healthy controls. We are exploring the molecular mechanisms behind Fli-1’s effects on lupus disease development using murine models of lupus, such as, MRL/lpr and NZM2410 mice, with specific gene knockout or overexpression techniques.
The role of Fli-1 on lymphocyte cell development and function. Using Fli-1 conditional knockout mice we can generate cell-specific Fli-1-deficincent mice. We are investigating the effects of Fli-1-deficiency on B and T cell development in vivo, and are determining the effects of Fli-1-deficiency on B and T cell function.
The role of Fli-1 in the innate immune system. Toll-like receptors (TLRs) are predominantly membrane-bound receptors that have been recognized as part of the innate immune system. TLRs are activated upon ligation by their particular pathogen-associated molecular patterns, and this activation leads to the induction of a rapid, usually inflammatory, immune response including the production of inflammatory cytokines and chemokines. We have found that Fli-1 is a key factor in regulating expression of several inflammatory cytokines and chemokines. We are studying the mechanism by which Fli-1 regulates pro-inflammatory cytokine production.
Lou N, Lennard Richard ML, Yu J, Kindy M, Zhang XK. The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2). Mol Immunol. 2017 Jan;81:59-66. doi: 10.1016/j.molimm.2016.11.007. Epub 2016 Nov 24. PMID: 27889620
Lennard Richard ML, Brandon D, Lou N, Sato S, Caldwell T, Nowling TK, Gilkeson G, Zhang XK. Acetylation impacts Fli-1-driven regulation of granulocyte colony stimulating factor. Eur J Immunol. 2016 Jul 19. doi: 10.1002/eji.201646315. PMID: 27431361
Lennard Richard ML., Nowling TK., Brandon D., Watsonc DK., Zhang XK. Fli-1 controls transcription from the MCP-1 gene promoter, which may provide a novel mechanism for chemokine and cytokine activation. Mol Immunol. 2015 Feb;63(2):566-73. doi: 10.1016/j.molimm.2014.07.013. Epub 2014 Aug 6. PMID: 25108845.
Sato S., Lennard Richard M., Brandon D.,Jones Buie J., Oates J., Gilkeson G., Zhang XK. A critical role for the transcription factor Fli-1 in lupus development by regulating expression of Interleukin 6. Arthritis Rheumatol. 2014 Dec;66(12):3436-44. doi: 10.1002/art.38818. PMID: 25155007.
Lennard Richard M, Sato S, Suzuki E, Williams S., Nowling TK., Zhang XK. The Fli-1 transcription factor regulates the expression of CCL5/RANTES. J Immunol. 2014; 193(6):2661-8. PMID: 25098295.
Sato S., Zhang XK. The Friend leukemia virus integration 1 (Fli-1) transcription factor affects lupus nephritis development by regulating inflammatory cell infiltration into the kidney. Cli. Exp. Immunol. 2014, 177(1):102-9. (PMC4089159).
Suzuki E, Karama E., Williams S., Watson DK., Gilkesona G., Zhang XK. Fli-1 transcription Factor Affects Glomerulonephritis Development by Regulating Expression of Monocyte chemoattractant protein-1 in Endothelial Cells in the Kidney. Cli Immunol. 2012; 145: 201-208
Suzuki E., Williams S., Gilkeson G., Watson DK., Zhanga XK. The Transcription Factor Fli-1 Regulates Monocytes, Macrophages, and Dendritic Cell Development in Mice. immunology. 2013, 139: 318-327.
Mathenia J, Reyes-Cortes E, Williams S, Molano I, Ruiz P, Watson D, Gilkeson G, Zhang X.Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice. Cli Exp Immunol 362: 362-371. 2010.
Molano, I, Mathenia, J., Ruiz, P., Gilkeson, G., Zhang, X. Decreased expression of Fli-1 in bone marrow derived hematopoietic cells significantly affects disease development in MRL/lpr mice. Cli Exp Immunol 180: 275-282. 2010.