- Associate Professor, Department of Pathology/MPMM
- Associate Professor, Committee on Immunology
- Associate Professor, Committee on Cancer Biology
- Associate Professor, Committee on Molecular Medicine/MPMM
Ph.D., University of Toronto, 1995
B.Sc. University of Toronto, 1989
The University of Chicago
924 East 57th Street
Chicago, Illinois 60637
Phone: (773) 702-4349
Transcriptional Regulation of Hematopoietic Development.
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.
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, Månsson R, Gurbuxani S, Sigvardsson M, Kee BL. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity. 2008 Aug 15;29(2):217-27.
Kee BL. E and ID proteins branch out. <http://www.ncbi.nlm.nih.gov/pubmed/19240756>
Nat Rev Immunol. 2009 Mar;9(3):175-84. Review.
Verykokakis M, Boos MD, Bendelac A, Adams EJ, Pereira P, Kee BL. Inhibitor of DNA binding 3 limits development of murine slam-associated adaptor protein-dependent "innate" gammadelta T cells.
PLoS One. 2010 Feb 19;5(2):e9303.
Verykokakis M, Boos MD, Bendelac A, Kee BL. SAP protein-dependent natural killer T-like cells regulate the development of CD8(+) T cells with innate lymphocyte characteristics.
Immunity. 2010 Aug 27;33(2):203-15. Epub 2010 Jul 30.
de Pooter RF, Kee BL. E proteins and the regulation of early lymphocyte development.
Immunol Rev. 2010 Nov;238(1):93-109.
Ramirez K., Chandler K.J., Spaulding C., Zandi S., Sigvardsson M., Graves B.J. and B.L. Kee (2012) Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1. Immunity 36(6):921-932.
Pereira de Sousa A., Berthault C., Granato A., Dias S., Ramond C., Kee B.L., Cumano A., Vieira P. (2012) Inhibitors of DNA binding proteins restrict T cell potential by repressing Notch1 expression in Flt3-negative common lymphoid progenitors. J. Immunol. in press