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Appointments:
Associate Professor
Department of Pathology/MPMM
Committee on Immunology
Committee on Cancer Biology
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Education:
Ph.D. University of Toronto, 1995
B.Sc. University of Toronto, 1989
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Contact:
Phone: (773) 702-4349
Fax:
(773) 834-5251
E-Mail:
bkee@bsd.uchicago.edu
Address:
The University of Chicago
AMB P319, (MC 1089)
5841 South Maryland Avenue
Chicago, Illinois 60637
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Related Research Interests:
Hematopoiesis
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Barbara Kee, Ph.D.
Transcriptional Regulation of Hematopoietic Development.
Research Summary
My lab is interested in
determining the basic mechanisms that regulate lymphocyte development
from
hematopoietic stem cells. We have focused on identifying the network of
transcriptional regulatory proteins that establish distinct cell
lineages. We
are also interested in determining how these networks interact with
other
regulatory pathways in the cell including growth factor and cytokine
signaling
and how these integrated networks control cell fate. Much of our work
has
centered on the transcription factors encoded by the E2A gene, which
are
required for proper development of B- and T-lymphocytes. We have
defined the
essential targets of E2A that promote B lineage specification (Early B
cell
Factor, EBF) and expansion (N-myc) in
response to cytokines. Current projects are directed at identifying the
transcriptional networks involved in natural killer cell and
T-lymphocyte
lineage specification, as well as lymphoid specification from
hematopoietic
stem cells.
A second area of interest in the
lab is to understand the mechanisms leading to lymphoid malignancies.
Multiple
conserved regulatory networks that promote hematopoietic stem cell or
lymphocyte survival and proliferation are aberrantly regulated in T
cell
lymphoma. We have found that lymphomas arising in E2A-deficient mice
invariably
have mutations in the Notch1 transmembrane receptor that lead to
prolonged and
heightened activation, and these tumors require Notch1 signaling for
their
survival. We are currently characterizing the Notch1 target genes that
promote
transformation of lymphocytes and we are determining how Notch1 and
other
oncogenic proteins become de-regulated in E2A-deficient thymocytes.
Selected Papers
Vilimas T, Mascarenhas J, Palomero T, Mandal M. Buonami S, Meng F, Macaroun S, Alegre ML, Kee BL, Ferrando A, Miele L, and I Aifantis. Targeting of the NF-kB signaling pathway in Notch1-induced T cell leukemia. Nat. Medicine 13(1):70-77, 2006.
Xu W and BL Kee. Growth Factor Independence 1b (Gfi1b) is an E2A Target Gene that Modulates Gata3 in T Cell Lymphomas. Blood 109(10):4406-4414. Epub. Feb. 1, 2007.
Welner RS, Pelayo R, Garrett K, Chen X, Perry SS, Kee BL, and PW Kincade. Notch independent formation of interferon-producing killer dendritic cells from T lineage biased CD62L+ progenitors in bone marrow. Blood, 109(11):4825-4931. Epub. Feb 22, 2007.
Boos MD, Eberl G, Yokota Y, and BL Kee. Mature Natural Killer Cell and Lymphoid Tissue Inducing Cell Development Requires Id2-Mediated Suppression of E-Protein Activity. J Exp Med 204(5):1119-1125, 2007.
Spaulding C, Reschly EJ, Zagort DE, Yashiro-Ohtani Y, Beverly LJ, Capobianco AJ, Pear WS, and BL Kee. Notch1 Co-opts Lymphoid Enhancer Factor 1 for Survival of Murine T Cell Lymphomas. Blood, 110(7):2650-2658. Epub. June 21, 2007.
Molinero LL, Zhou P, Wang Y, Harlin H, Cosmano J, Yokota Y, Kee BL, Abraham C, Alegre ML. Epidermal Langerhans cells play a major role in skin allograft rejection in mice with NF-kB-impaired T cells. Am J Transplant 8(1):2650-2658. Epub June 21, 2007.
Bhalla S, Spaulding C, Brumbaugh RL, Zagort DE, Massari ME, Murre C, and BL Kee. Differential roles for the E2A activation domains in B lymphocytes and macrophages. J Immunol 180(3):1694-1703, 2008.
Dias S, Mansson R, Gurbuxani S, Sigvardsson M, and BL Kee. E2A transcription factors promote lymphoid specification. Manuscript submitted, 2008.
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Faculty and Research
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