Training:
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B.Sc., 1985: University of California, Los Angeles
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Ph.D., 1991: University of California, San Diego
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Post Doctoral, 1992-1998: National Cancer Institute, Bethesda, MD Summary of the focus of the research of Dr. Dent
One sentence description of my research interests: Transcripional control of cytokine gene expression, lymphocyte differentiation and lymphomagenesis. Description and summary of research focus of the laboratory:
My lab is interested in the regulation of gene expression in lymphocytes, particularly relating to cytokine gene expression, cellular differentiation, and cellular transformation to cancer. We study cytokine gene expression in conventional CD4 T helper cells, NK T cells and macrophages. Our current emphasis is on the expression of specific cytokines in defined subsets of cells, such as the expression of IL-10 in T helper type 2 cells, or the expression of IL-4 in CD4+ NK T cells. In terms of cellular differentiation, we analyze the differentiation of naive T helper lymphocytes into Th2 cytokine secreting effector cells and the differentiation of mature B lymphocytes into germinal center B cells and antibody-secreting plasma cells. Finally we are interested in how lymphocyte growth and differentiation is deregulated during the transition of a normal lymphocyte into a transformed or cancerous lymphocyte. A major focus of my lab has been on the transcription factor BCL-6, which participates in all three of these critical processes in lymphocytes: cytokine gene expression, differentiation, and neoplastic transformation. Recently, we have developed a novel cell culture system to study the role of BCL-6 in B cell transformation. We have found that BCL-6 plays a key role in immortalizing B cells and preventing senescence in response to continuous proliferation. BCL-6 also inhibits terminal differentiation of B cells into plasma cells. Currently, we are trying to understand which genes are regulated by BCL-6 that function to inhibit senescence and terminal differentiation. These studies will provide important insights into the development of B cell lymphoma, and will also give new insights into the mechanism of cellular aging. Publications
Toney, L.M., Cattoretti, G., Graf, J.A., Merghoub, T., Pandolfi, P.-P., Dalla-Favera, R.D., Ye, B.H., and Dent, A.L. "BCL-6 Regulates Chemokine Gene Transcription in Macrophages" Nature Immunology, 1, 214 (2000). Dent, A.L., Vasanwala, F.H., Toney, L.M. "Regulation of Gene Expression by the Proto-oncogene BCL-6" Crit. Rev. Onc. Hemat. 41, 1 (2002). Vasanwala, F.H., Kusam, S., Toney, L.M. and Dent, A.L. "Repression of AP-1 Function: a Mechanism for the Regulation of Blimp-1 Expression and B Lymphocyte Differentiation by the BCL-6 Proto-oncogene" J. Immunol. 169:1922-1929 (2002). Kusam, S., Toney, L.M., Sato, H. and Dent, A.L. "Inhibition of Th2 differentiation and GATA-3 expression by BCL-6" J. Immunol. 170: 2435-2441 (2003). Kusam, S., Vasanwala, F., and Dent, A.L. "The Transcriptional Repressor BCL-6 Immortalizes Germinal Center-like B Cells in the Absence of p53 Function", Oncogene, 23: 839-844 (2004). Search Pub Med Return to Homepage |
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