Barbara Kee, PhD
Contact
University of Chicago5841 S. Maryland Ave. MC1089
Chicago, IL 60637
Phone: (773) 702-4349
Fax: (773) 834-5251
Lab: (773) 834-7914
Lab Room No: AMB J-310
bkee@bsd.uchicago.edu
Committee Membership
Committee on ImmunologyCommittee on Cancer Biology
Committee on Developmental Biology
Research Interest
The development of mature hematopoietic cells requires the coordinated activity of many transcription factors that regulate differentiation, survival, and proliferation. My lab is interested in understanding how these processes are controlled during commitment of multipotent cells to the lymphoid lineages. We have focused on the basic helix-loop-helix transcription factors encoded by the E2A gene and their antagonists, the Id proteins. E2A proteins are required for B lymphocyte development whereas their antagonist, Id2, is required for Natural Killer cell and lymphoid tissue initiating cell development. All of these lineages are thought to develop from a common lymphoid progenitor (CLP) suggesting that control of E2A activity may play a direct role in the lineage choice of the CLP. We have determined that E2A proteins are required for B-lymphocyte development in part because they induce the expression of EBF, another transcription factor that promotes B-lineage gene expression. In addition to its role in the regulation of EBF, we have shown that E2A proteins are required to maintain proliferation and survival of B-lymphocyte progenitors. E2A proteins are also required for proper T-lymphocyte development as demonstrated by the 5-fold decrease in T-lymphocyte progenitors in E2A-deficient mice. In addition, these mice succumb to T-lymphocyte progenitor lymphoma indicating that E2A proteins also function to suppress transformation in these cells.Selected Publications
- Spaulding C, Reschly EJ, Zagort DE, Yashiro-Ohtani Y, Beverly LJ, Capobianco A, Pear WS, Kee BL. Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. Blood. 2007 Oct 1;110(7):2650-8.
- Nutt SL, Kee BL. The transcriptional regulation of B cell lineage commitment. Immunity. 2007 Jun;26(6):715-25.
- Boos MD, Yokota Y, Eberl G, Kee BL. Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med. 2007 May 14;204(5):1119-30. Epub 2007 Apr 23.
- Xu W, Kee BL. Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas. Blood. 2007 May 15;109(10):4406-14.
- Reschly EJ, Spaulding C, Vilimas T, Graham WV, Brumbaugh RL, Aifantis I, Pear WS, Kee BL. Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms.
Blood. 2006 May 15;107(10):4115-21. - Kee BL.
Helix-loop-helix proteins in lymphocyte lineage determination.
Curr Top Microbiol Immunol. 2005;290:15-27. - Kee BL. Id3 induces growth arrest and caspase-2-dependent apoptosis in B lymphocyte progenitors. J Immunol. 2005 Oct 1;175(7):4518-27.
- Osborne BA, Kee BL. Lymphoid development: it's not 'all Greek to us' any more. Nat. Immunol. 2005 Feb;6(2):119-23
- Seet CS, Brumbaugh RL, Kee BL. Early B Cell Factor Promotes B Lymphopoiesis with Reduced Interleukin 7 Responsiveness in the Absence of E2A. J Exp Med. 2004 Jun 21;199(12):1689-700.
- Kee BL, Bain G, Murre C. IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors. EMBO J. 2002 Jan 15;21(1-2):103-13.
- Kee BL, Murre C. Transcription factor regulation of B lineage commitment. Curr Opin Immunol. 2001 Apr;13(2):180-5.
- Kee BL, Rivera RR, Murre C. Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta. Nat Immunol. 2001 Mar;2(3):242-7.
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