Appointments:

Associate Professor
Department of Pathology/MPMM

Committee on Immunology
Committee on Cancer Biology

Education:

Ph.D. University of Toronto, 1995

B.Sc. University of Toronto, 1989

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

Related Research Interests:

Hematopoiesis

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

Kee BL and Murre C. (1998). Induction of Early B cell Factor (EBF) and multiple B lineage-associated genes by the basic helix-loop-helix transcription factor E12. The Journal of Experimental Medicine 188:699-713.

Kee BL, Rivera RR and Murre C. (2001). Id3 inhibits B lymphocyte progenitor growth and survival in response to Transforming Growth Factor-b . Nature Immunology, 2:242-247.

Kee BL, Bain G and Murre C. (2002). IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors. EMBO J., 21:103-113.

Perkins EJ, Kee BL and Ramsden DA (2004). Histone 3 Lysine 4 methylation during the pre-B to immature B-cell transition. Nucl. Acid Res. 32:1-6.

Seet CS, Brumbaugh RL, Kee BL. (2004). Early B Cell Factor Promotes B Lymphopoiesis with Reduced Interleukin 7 Responsiveness in the Absence of E2A. J Exp Med. Jun 21;199(12):1689-700.

Osborne BA and Kee BL. (2005) Lymphoid development: it's not 'all Greek to us' anymore. Nat. Immunol. 6:119-123.

Kee BL. (2005) Id3 induces growth arrest and caspase-2-dependent apoptosis in B lymphocyte progenitors. J. Immunol. 175:4518-4527.

Reschly EJ, Spaulding C, Vilimas T, Graham WV, Brumbaugh RL, Aifantis I, Pear WS and Kee BL. (2006) Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and –independent mechanisms. Blood 107:4115-4121.

Faculty and Research

Programs

Cancer Biology

Immunology

Microbiology

Molecular Metabolism
and Nutrition

Molecular Pathogenesis and
Molecular Medicine