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Research – Overall Goals
Our laboratory is interested in understanding the molecular mechanisms that control B lymphocyte development and diseases. B cells make antibody and play an essential role in the immune response. B cell development can be divided into discrete stages which are characterized by the sequential rearrangement of immunoglobulin heavy and light chain loci and the expression of distinct cell surface markers. At each developmental stage B cell will undergo selection and only a few “right” cells will be chosen to move on to the next stage. Disruption of this highly regulated developmental process often results in abnormal B cell development, which could further lead to diseases such as leukemia/lymphoma. At the molecular level, B cell development is orchestrated by a group of transcription factors. IRF-4 and IRF-8 are two specialized members of the IRF family of transcription factor that express exclusively in the immune system. Previously studies have shown that in the absence of IRF4,8, B cell development is arrested at the pre-B cell stage. Intriguingly, the mutant pre-B cells are proliferating constantly and show a defect in exiting from cell cycle. The finding that B cell development is blocked at the pre-B stage in IRF4 and IRF8 compound mutant mice (IRF4,8-/-) strongly indicates that IRF4,8 are essential for the development of pre-B cell. One of the interests in the lab is to use IRF4,8-/- mice as a model to dissect the molecular mechanism by which IRF4,8 control pre-B cell growth and differentiation.
Abnormal B cell development often leads to diseases such as leukemia and lymphoma. Another interest in the lab is to investigate roles of IRF4,8 in the pathogenesis of leukemia and lymphoma. In addition, we are also interested in identifying genes whose expression are regulated by IRF4,8 in the immune system.
A wide range of approaches are utilized in the lab to address our research interests, including RNAi mediated gene knockdown, retroviral gene transduction, chromatin immunoprecipitation assay, flow cytometry analysis, gene chip analysis and transgenic and knockout mice.
Keywords: transcription factor, B cell development, gene regulation, cell growth and differentiation, leukemia and lymphoma.
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Recent Publications:
Lu R. (2008) Interferon regulatory factor 4 and 8 in B cell development. Trends in Immunology. Invited Review, in press.
Pathak S., Ma S., Trinh L. and Lu R. (2008) A role for interferon regulatory factor 4 in receptor editing. Molecular Cellular Biology. 28(8): 2815-2824.
Ma S., Pathak S., Trinh L. and Lu R. (2008) Interferon regulatory factory 4 & 8 induce the expression of Ikaros and Aiolos to downregulate pre-BCR and promote cell cycle withdrawal in pre-B cell development. Blood 111(3): 1396-1403.
Ma, S., Turesky A., Trinh L. and Lu, R. (2006) IFN regulatory factor 4 and 8 promote light chain locus activation in pre-B cell development. J Immunol. 177: 7898-7904.
Lu, R., Medina K.L., Lancki, D. and Singh, H. (2003) IRF4,8 orchestrate the pre-B to B transition in lymphocyte development. Genes&Development 17: 1703-1708.
Lu, R., Moore, P.A. and Pitha, P.M. (2002) Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene accessibility. J. Biol. Chem. 277: 16592-16598.
Lu, R. and Pitha, P.M. (2001) Monocyte differentiation to macrophage requires interferon regulatory factory 7. J. Biol. Chem. 276: 45491-45496.
Lu, R., Au, W-C., Yeow, W-S., Hageman, N. and Pitha, P.M. (2000) Regulation of the promoter activity of interferon regulatory factor-7 gene: activation by interferon and silencing by hypermethylation. J. Biol. Chem. 275: 31805-31812.
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