Asymmetric cell division; stem cell self-renewal; epigenetic and transcription factor-mediated control of gene expression; host response to infection and cancer; effector and memory T lymphocyte differentiation;
asymmetric cell division, stem cells, transcription, lymphocyte
Diversifying cell fate in essential and unwanted cells
Using lymphocytes as a model system, we recently proposed that asymmetric cell division may be a way for many mobile, non-polarized cells to generate cell fate diversity among their progeny. We are using static and time-lapsed imaging, genetic, and biochemical methods to better understand the nature and extent of asymmetric cell division in multi-celled beings. It is predicted that this will have immediate relevance for the way in which blood stem cells and metastatic cancer stem cells can generate diverse progeny despite their lack of obvious polarity. Studies of lymphocyte differentiation during the immune response should continue to become an increasingly useful model for inquiry into the fundamental problem of regulated gene expression in dividing, differentiating, and highly mobile cells.
Study the mechanisms involved mediating asymmetric division of T cells, blood stem cells and cancer stem cells.
Characterize the mechanisms of action of novel transcriptional regulators of immune cell differentiation.
Maria Ciocca-Graduate Student
Burton Barnett-Graduate Student
Gordon SM, Carty SA, Kim JS, Zou T, Smith-Garvin J, Alonzo ES, Haimm E, Sant'angelo DB, Koretzky GA, Reiner SL, Jordan MS.: Requirements for Eomesodermin and Promyelocytic Leukemia Zinc Finger in the Development of Innate-Like CD8+ T Cells. J Immunol 186(8): 4573-8, Apr 2011.
Barnett BE, Ciocca ML, Goenka R, Barnett LG, Wu J, Laufer TM, Burkhardt JK, Cancro MP, Reiner SL.: Asymmetric B Cell Division in the Germinal Center Reaction. Science 2011.
Chang, J.T., M.L. Ciocca, I. Kinjyo, V.R. Palanivel, C.E. McClurkin, C.S. DeJong, E.C. Mooney, J.S. Kim, N.C. Steinel, J. Oliaro, C.Y. Yin, B.I. Florea, H.S. Overkleeft, L.J. Berg, S.M. Russell, G.A. Koretzky, M.S. Jordan, and S.L. Reiner: Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division. Immunity 34: 492-504, 2011.
Kao, C., K.J. Oestreich, M. Paley, A. Crawford, J.M. Angelosanto, M.A. Ali, A.M. Intlekofer, J.M. Boss, S.L. Reiner, A.S. Weinmann and E.J. Wherry: T-bet represses expression of PD-1 and sustains virus-specific CD8 T cell responses during chronic infection. Nat Immunol 12: 663-671, 2011.
Kinjyo I, Gordon SM, Intlekofer AM, Dowdell K, Mooney EC, Caricchio R, Grupp SA, Teachey DT, Rao VK, Lindsten T, Reiner SL.: Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin. J Immunol 185(12): 7151-5, Dec 2010.
Oliaro J, Van Ham V, Sacirbegovic F, Pasam A, Bomzon Z, Pham K, Ludford-Menting MJ, Waterhouse NJ, Bots M, Hawkins ED, Watt SV, Cluse LA, Clarke CJ, Izon DJ, Chang JT, Thompson N, Gu M, Johnstone RW, Smyth MJ, Humbert PO, Reiner SL, Russell SM.: Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms. J Immunol 185(1): 367-75, july 2010.
Banerjee A, Schambach F, DeJong CS, Hammond SM, Reiner SL.: Micro-RNA-155 inhibits IFN-gamma signaling in CD4+ T cells. Eur J Immunol 40(1): 225-31, 2010.
Shin H, Blackburn SD, Intlekofer AM, Kao C, Angelosanto JM, Reiner SL, Wherry EJ.: A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Immunity 31(2): 309-20, 2009.
Weinreich MA, Takada K, Skon C, Reiner SL, Jameson SC, Hogquist KA.: KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors. Immunity 31(1): 122-30, 2009.
Reiner SL: Decision making during the conception and career of CD4+ T cells. Nat Rev Immunol. 9(2): 81-2, 2009.
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Last updated: 02/08/2013
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