University of South Florida

Cancer Biology Ph.D. Program at the

Kenneth L. Wright, Ph.D. Associate Professor in the Department of Oncologic Sciences Member-in-Residence of the Moffitt Cancer Center Director, Cancer Biology Ph.D. Program E-mail: Ken.Wright@moffitt.org Phone: (813)745-3918

Training
B.S.: University of Florida, Chemistry, 1984.
Ph.D.: University of Massachusetts, Worcester, MA, 1990.
Postdoctoral Fellow: Lineberger Comprehensive Cancer Center at University of North Carolina.

Research Interests
Dr. Wright’s laboratory is investigating the function and mechanism of action of the B cell differentiation factor PRDM1 (Blimp1). PRDM1 is a DNA binding protein that silences expression of specific genes and drives a global gene expression reprogramming during differentiation in immune cells. In addition PRDM1 is a tumor suppressor and mutations of PRDM1 define a specific class of Diffuse Large B Cell Lymphoma.

Our current focus is to define the specific function of PRDM1 in three distinct settings.

First, in Mantle Cell Lymphoma our studies have shown that therapeutic treatment with proteasome inhibitors or histone deacetylase inhibitors activates and depends upon PRDM1 expression. The mechanism of activation and the identification of critical PRDM1 targets are currently under investigation.

Secondly, we have made the novel observation that PRDM1 is expressed in Natural Killer (NK) cells. Our data has revealed a critical role in attenuating NK activation and secretion of cytokines. In addition others have now shown that PRDM1 affects the proliferative capacity of NK cells. The laboratory is currently investigating the mechanism of PRDM1 activity in NK biology.

Lastly we have shown that PRDM1 is induced during dendritic cell maturation and is responsible for silencing MHC antigen processing through directly silencing the CIITA transactivator. The role of PRDM1 in fine tuning the dendritic cell response to pathogen signals is an area of specific interest. In all studies we use state-of-the-art molecular and cellular approaches as well as global genomic approaches to characterize the function of the PRDM1 complex and its downstream targets.

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Selected Publications

Gyory, I., Ghosh, N. and Wright, K.L. (2003) Identification of a functionally impaired PRDI-BF1 transcriptional repressor in myeloma cells. J. Immunology 170:3125-3133.

Gyory, I., Wu, J., Fejer G, Seto E, and Wright, K.L. (2004) PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nature Immunology, 5:299-308.

Desai, S., Bolick, S.C.E., Maurin, M., and Wright, K.L. (2009) Pu.1 regulates positive regulatory domain I-binding factor 1/Blimp-1 transcription in lymphoma cells Journal of Immunology, 183:5778-5787.

Desai, S., Maurin, M., Smith, M.A., Bolick, S.C.E., Dessureault, S., Tao, J., Sotomayor, E., and Wright, K.L. (2010) PRDM1 is required for Mantle Cell Lymphoma response to Bortezomib. Molecular Cancer Research, 8:907-918.

Smith, M.A., Maurin, M., Cho, H., Becknell, B., Freud A.G., Wei, S., Djeu, J., Celis, E., Caligiuri, M., and Wright, K.L. (2010) PRDM1/Blimp-1 controls effector cytokine production in human NK cells. Journal of Immunology, 185:6058-6067.

Smith, M.A., Wright, G., Wu, J., Tailor, P., Ozato, K., Chen, X., Wei, S., Piskurich, J.F., Ting, J. P.-Y., and Wright, K.L. (2011) Positive Regulatory Domain I (PRDM1) and IRF8/PU.1 Counter Regulate MHC Class II Transactivator (CIITA) Expression during Dendritic Cell Maturation. Journal of Biological Chemistry, in press [Epub Jan 7, 2011].