Kenneth L. Wright, PhD

Where You Are:
Kenneth L. Wright, PhD

Associate Member

Office  (813) 745-3918

Education And Training
  • Postdoctoral Fellow, UNC Lineberger Comp. Cancer Ctr., 1996 - Immunology
  • PhD, University of Massachusetts, 1990 - Cell Biology
  • BS, University of Florida, 1984 - Chemistry


My primary interest is the molecular mechanisms controlling genes involved in antigen presentation. Antigen presentation is a key step in eliciting a normal immune response and it can play an important role in tumor rejection and autoimmunity. The laboratory is currently focused on two transcription factors, CIITA and PRDI-BF1. CIITA is a transcriptional activator and master regulator of the MHC Class II family of antigen presentation genes. PRDI-BF1 is a transcriptional repressor that silences CIITA and promotes terminal differentiation of immune cells. We are examining these factors in the two primary cell types. The first is in B-lymphocytes and during their terminal differentiation into antibody secreting plasma cells. The second is in primary human and mouse dendritic cells.

In B-lymphocytes our laboratory has previously mapped the B-cell specific promoter of CIITA. This was done through a combination of in vivo and in vitro DNA binding studies. One of the more significant outcomes of this study was the discovery that the transcriptional silencer PRDI-BF1 down-regulates CIITA and MHC class II expression in multiple myeloma cells. Multiple myeloma is a disease of malignant plasma cells. PRDI-BF1 also down-regulates c-myc, Pax5 and interferon-beta expression. The chromosomal location of PRDI-BF1, 6q21, is deleted in a high percentage of B cell lymphomas as well as other types of cancer. Our investigations have identified a natural truncated form of PRDI-BF1 that is lacking a critical N-terminal domain in multiple myeloma cells and have shown that this isoform is impaired in repressing CIITA transcription. Deletion of this domain from the other two PRDI-BF1 family members converts these proteins from growth suppressive to oncogenic. The role of PRDI-BF1 and its truncated form in the development and progression of multiple myeloma is currently under investigation.

We are also characterizing the dendritic cell specific promoter of CIITA in both human and mouse primary dendritic cells. CIITA transcription is high in immature DC cells but is rapidly turned off when the cells receive a maturation signal. We have identified several key transcription factors required for DC expression. The role of these factors as well as the silencing of expression observed upon dendritic cell maturation is an area of continued investigation using multiple approaches including gene knock-out mouse models. These studies will provide vital information for targeting expression of tumor specific antigens directly to the professional antigen presenting dendritic cell with out altering expression in other cells.

The mechanism of action of PRDI-BF1 is also being studied. PRDI-BF1 is known to recruit histone deacetylases as part of its transcription repression activity. We have now identified that specific histone methyltransferases are also recruited by PRDI-BF1 and play an important role in its repression activity. This indicates that PRDI-BF1 may serve as a scaffold molecule to bring multiple chromatin modifying enzymes to specific promoters such as CIITA. Investigations are continuing to dissect the role of the histone methyltransferases and PRDI-BF1 in myeloma, lymphoma and dendritic cell development. In addition, a small molecule inhibitor screen is ongoing to identify compounds that interrupt histone methyltransferase activity as potential therapeutics in the treatment of myeloma and lymphoma.

  • Ren Y, Zhang Y, Liu RZ, Fenstermacher DA, Wright KL, Teer JK, Wu J. JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations. Sci Rep. 2013 Oct;3:3042. Pubmedid: 24154688.
  • Zhang X, Zhao X, Fiskus W, Lin J, Lwin T, Rao R, Zhang Y, Chan JC, Fu K, Marquez VE, Chen-Kiang S, Moscinski LC, Seto E, Dalton WS, Wright KL, Sotomayor E, Bhalla K, Tao J. Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas. Cancer Cell. 2012 Oct;22(4):506-523. Pubmedid: 23079660. Pmcid: PMC3973134.
  • Zhang X, Chen X, Lin J, Lwin T, Wright G, Moscinski LC, Dalton WS, Seto E, Wright K, Sotomayor E, Tao J. Myc represses miR-15a/miR-16-1 expression through recruitment of HDAC3 in mantle cell and other non-Hodgkin B-cell lymphomas. Oncogene. 2012 Jun;31(24):3002-3008. Pubmedid: 22002311. Pmcid: PMC3982396.
  • Cubedo E, Maurin M, Jiang X, Lossos IS, Wright KL. PRDM1/Blimp1 downregulates expression of germinal center genes LMO2 and HGAL. FEBS J. 2011 Sep;278(17):3065-3075. Pubmedid: 21722313. Pmcid: PMC3158840.
  • Vrzalikova K, Vockerodt M, Leonard S, Bell A, Wei W, Schrader A, Wright KL, Kube D, Rowe M, Woodman CB, Murray PG. Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas. Blood. 2011 Jun;117(22):5907-5917. Pubmedid: 21411757. Pmcid: PMC3293751.
  • Wang H, Cheng F, Woan K, Sahakian E, Merino O, Rock-Klotz J, Vicente-Suarez I, Pinilla-Ibarz J, Wright KL, Seto E, Bhalla K, Villagra A, Sotomayor EM. Histone deacetylase inhibitor LAQ824 augments inflammatory responses in macrophages through transcriptional regulation of IL-10. J Immunol. 2011 Apr;186(7):3986-3996. Pubmedid: 21368229. Pmcid: PMC3998678.
  • Dubovsky JA, Wang D, Powers JJ, Berchmans E, Smith MA, Wright KL, Sotomayor EM, Pinilla-Ibarz JA. Restoring the functional immunogenicity of chronic lymphocytic leukemia using epigenetic modifiers. Leuk Res. 2011 Mar;35(3):394-404. Pubmedid: 20863567.
  • Smith MA, Wright G, Wu J, Tailor P, Ozato K, Chen X, Wei S, Piskurich JF, Ting JP, Wright KL. Positive regulatory domain I (PRDM1) and IRF8/PU.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation. J Biol Chem. 2011 Mar;286(10):7893-7904. Pubmedid: 21216962. Pmcid: PMC3048676.
  • Lin J, Lwin T, Zhao JJ, Tam W, Choi YS, Moscinski LC, Dalton WS, Sotomayor EM, Wright KL, Tao J. Follicular dendritic cell-induced microRNA-mediated upregulation of PRDM1 and downregulation of BCL-6 in non-Hodgkin's B-cell lymphomas. Leukemia. 2011 Jan;25(1):145-152. Pubmedid: 20966935. Pmcid: PMC3083119.
  • Lwin T, Lin J, Choi YS, Zhang X, Moscinski LC, Wright KL, Sotomayor EM, Dalton WS, Tao J. Follicular dendritic cell-dependent drug resistance of non-Hodgkin lymphoma involves cell adhesion-mediated Bim down-regulation through induction of microRNA-181a. Blood. 2010 Dec;116(24):5228-5236. Pubmedid: 20841506. Pmcid: PMC3012540.
  • Smith MA, Maurin M, Cho HI, Becknell B, Freud AG, Yu J, Wei S, Djeu J, Celis E, Caligiuri MA, Wright KL. PRDM1/Blimp-1 controls effector cytokine production in human NK cells. J Immunol. 2010 Nov;185(10):6058-6067. Pubmedid: 20944005. Pmcid: PMC3864810.
  • Chen L, Li Z, Zwolinska AK, Smith MA, Cross B, Koomen J, Yuan ZM, Jenuwein T, Marine JC, Wright KL, Chen J. MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. EMBO J. 2010 Aug;29(15):2538-2552. Pubmedid: 20588255. Pmcid: PMC2928696.
  • Desai S, Maurin M, Smith MA, Bolick SC, Dessureault S, Tao J, Sotomayor E, Wright KL. PRDM1 is required for mantle cell lymphoma response to bortezomib. Mol Cancer Res. 2010 Jun;8(6):907-918. Pubmedid: 20530581. Pmcid: PMC2891394.
  • Desai S, Bolick SC, Maurin M, Wright KL. PU.1 regulates positive regulatory domain I-binding factor 1/Blimp-1 transcription in lymphoma cells. J Immunol. 2009 Nov;183(9):5778-5787. Pubmedid: 19828640. Pmcid: PMC3164282.
  • Villagra A, Cheng F, Wang HW, Suarez I, Glozak M, Maurin M, Nguyen D, Wright KL, Atadja PW, Bhalla K, Pinilla-Ibarz J, Seto E, Sotomayor EM. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol. 2009 Jan;10(1):92-100. Pubmedid: 19011628. Pmcid: PMC3925685.
  • Wright KL, Duncan M, Sharkey KA. Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br J Pharmacol. 2008 Apr;153(2):263-270. Pubmedid: 17906675. Pmcid: PMC2219529.
  • Bewry NN, Bolick SC, Wright KL, Harton JA. GTP-dependent recruitment of CIITA to the class II major histocompatibility complex promoter. J Biol Chem. 2007 Sep;282(36):26178-26184. Pubmedid: 17623662.
  • Zhao M, Flynt FL, Hong M, Chen H, Gilbert CA, Briley NT, Bolick SC, Wright KL, Piskurich JF. MHC class II transactivator (CIITA) expression is upregulated in multiple myeloma cells by IFN-gamma. Mol Immunol. 2007 Apr;44(11):2923-2932. Pubmedid: 17300840.
  • Coopman K, Smith LD, Wright KL, Ward SG. Temporal variation in CB2R levels following T lymphocyte activation: evidence that cannabinoids modulate CXCL12-induced chemotaxis. Int Immunopharmacol. 2007 Mar;7(3):360-371. Pubmedid: 17276894.
  • Chen H, Gilbert CA, Hudson JA, Bolick SC, Wright KL, Piskurich JF. Positive regulatory domain I-binding factor 1 mediates repression of the MHC class II transactivator (CIITA) type IV promoter. Mol Immunol. 2007 Mar;44(6):1461-1470. Pubmedid: 16765445. Pmcid: PMC1987354.
  • Wright K, Ting J. Epigenetic regulation of MHC-II and CIITA genes. Trends Immunol. 2006 Aug;27(9):405-412. Pubmedid: 16870508.
  • Rastogi S, Joshi B, Dasgupta P, Morris M, Wright K, Chellappan S. Prohibitin facilitates cellular senescence by recruiting specific corepressors to inhibit E2F target genes. Mol Cell Biol. 2006 Jun;26(11):4161-4171. Pubmedid: 16705168. Pmcid: PMC1489107.
  • Piskurich JG, Gilbert CA, Ashley BD, Zhao M, Chen H, Wu J, Bolick SC, Wright KL. Expression of the MHC class II transactivator (CIITA) type IV promoter in B lymphocytes and regulation by IFN-gamma. Mol Immunol. 2006 Mar;43(6):519-528. Pubmedid: 15950283. Pmcid: PMC1482792.
  • Niu G, Wright KL, Ma Y, Wright GM, Huang M, Irby R, Briggs J, Karras J, Cress WD, Pardoll D, Jove R, Chen J, Yu H. Role of Stat3 in regulating p53 expression and function. Mol Cell Biol. 2005 Sep;25(17):7432-7440. Pubmedid: 16107692.
  • Wang AH, Gregoire S, Zika E, Xiao L, Li CS, Li H, Wright KL, Ting J, Yang XJ. Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners of class IIa histone deacetylases. J Biol Chem. 2005 Aug;280(32):29117-29127. Pubmedid: 15964851.
  • Gyory I, Wu J, Fejer G, Seto E, Wright K. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nat Immunol. 2004;5(3):299-308. Pubmedid: 14985713.
  • Rezai-Zadeh N, Zhang X, Namour F, Fejer G, Wen YD, Yao YL, Gyory I, Wright K, Seto E. Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Gene Dev. 2003 Apr;17(8):1019-1029. Pubmedid: 12704081. Pmcid: PMC196041.
  • Gyory I, Fejer G, Ghosh N, Seto E, Wright KL. Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines. J Immunol. 2003 Mar;170(6):3125-3133. Pubmedid: 12626569.
  • Wong AW, Ghosh N, McKinnon KP, Reed W, Piskurich JF, Wright KL, Ting JP. Regulation and specificity of MHC2TA promoter usage in human primary T lymphocytes and cell line. J Immunol. 2002 Sep;169(6):3112-3119. Pubmedid: 12218128.
  • Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang T, Sinibaldi D, Coppola D, Heller R, Ellis LM, Karras J, Bromberg J, Pardoll D, Jove R, Yu H. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 2002 Mar;21(13):2000-2008. Pubmedid: 11960372.
  • Goodwin B, Xi H, Tejiram R, Eason D, Ghosh D, Wright K, Nagarajan U, Boss J, Blanck G. Varying functions of specific major histocompatibility class II transactivator promoter III and IV elements in melanoma cell lines. Cell Growth Differ. 2001;12(6):327-335. Pubmedid: 11432807.
  • Jennings R, Alsarraj M, Wright K, Munoz-Antonia T. Regulation of the human transforming growth factor beta type II receptor gene promoter by novel Sp1 sites. Oncogene. 2001;20(47):6899-6909. Pubmedid: 11687969.
  • Ghosh N, Gyory I, Wright G, Wood J, Wright K. Positive regulatory domain I binding factor 1 silences class II transactivator expression in multiple myeloma cells. J Biol Chem. 2001;276(18):15264-15268. Pubmedid: 11279146.
  • Dovhey SE, Ghosh NS, Wright KL. Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line. Cancer Res. 2000 Oct;60(20):5789-5796. Pubmedid: 11059775.
  • Chatterjee-Kishore M, Wright K, Ting J, Stark G. How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. Embo J. 2000;19(15):4111-4122. Pubmedid: 10921891.
  • Brickey WJ, Wright KL, Zhu XS, Ting JP. Analysis of the defect in IFN-gamma induction of MHC class II genes in G1B cells: identification of a novel and functionally critical leucine-rich motif (62-LYLYLQL-68) in the regulatory factor X 5 transcription factor. J Immunol. 1999 Dec;163(12):6622-6630. Pubmedid: 10586057.
  • Wright K, Morgan D, Yu X, Goss J, Salbaum J, Duff K, Gordon M. Mice transgenic for a human amyloid precursor protein promoter-lacZ reporter construct. J Magn Reson Imaging. 1999;13(1-2):111-120.
  • Jackson R, Antonia S, Wright K, Moon S, Nepvue A, Munoz-Antonia T. Human cut-like repressor protein binds TGFbeta type II receptor gene promoter. Arch Biochem Biophys. 1999;371(2):290-300. Pubmedid: 10545217.
  • Jackson R, Antonia S, Wright K, Moon N, Nepvue A, Munoz-Antonia T. Human cut-like repressor protein regulates TGF-beta type II receptor gene promotor. Biochem Biophys Res Commun. 1999;371(2):290-300.
  • Xi H, Eason D, Ghosh D, Dovhey S, Wright K, Blanck G. Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) type IV promoter by interferon regulatory factors 1 and 2. Oncogene. 1999;18(43):5889-5903. Pubmedid: 10557076.
  • Ghosh N, Piskurich J, Wright G, Hassani K, Ting J, Wright K. A novel element and a TEF-2-like element activate the major histocompatibility complex class II transactivator in B-lymphocytes. J Biol Chem. 1999;274(45):32342-32350. Pubmedid: 10542275.
  • Wright K, Chin K, Linhoff M, Skinner C, Brown J, Boss J, Stark G, Ting J. CIITA stimulation of transcription factor binding to major histocompatibility complex class II and associated promoters in vivo. Proc Natl Acad Sci U S A. 1998 May;95(11):6267-6272. Pubmedid: 9600954. Pmcid: PMC27653.
  • Ting J, Wright K, Chin K, Brickey W, Li G. The DMB promoter: delineation, in vivo footprint, trans-activation, and trans-dominant suppression. J Immunol. 1997 Dec;159(11):5457-5462. Pubmedid: 9548486.
  • Linhoff M, Wright K, Ting J. CCAAT-binding factor NF-Y and RFX are required for in vivo assembly of a nucleoprotein complex that spans 250 base pairs: the invariant chain promoter as a model. Mol Cell Biol. 1997 Aug;17(8):4589-4596. Pubmedid: 9234716. Pmcid: PMC232312.
  • Katula KS, Wright KL, Paul H, Surman DR, Nuckolls FJ, Smith JW, Ting JP, Yates J, Cogswell JP. Cyclin-dependent kinase activation and S-phase induction of the cyclin B1 gene are linked through the CCAAT elements. Cell Growth Differ. 1997 Jul;8(7):811-820. Pubmedid: 9218875.
  • Zimmermann A, Wright K, Ting J, Mitchell B. Regulation of inosine 5' monophosphate dehydrogenase type II gene expression in human T cells: role for a novel 5' palindromic octamer sequence. J Biol Chem. 1997;272:22913-22923. Pubmedid: 9278455.
  • White L, Wright K, Felix N, Ruffner H, Reis L, Pine R, Ting J. Regulation of LMP2 and TAP1 genes by IRF-1 explaines the paucity of CD8+ T cells in IRF-1(-/-) mice. Immunity. 1996;5:365-376. Pubmedid: 8885869.
  • Chin KC, Mao C, Skinner C, Riley JL, Wright KL, Moreno CS, Stark GR, Boss JM, Ting JP. Molecular analysis of G1B and G3A IFN gamma mutants reveals that defects in CIITA or RFX result in defective class II MHC and Ii gene induction. Immunity. 1994 Nov;1(8):687-697. Pubmedid: 7600294.
  • Wright KL, Vilen BJ, Itoh-Lindstrom Y, Moore TL, Li G, Criscitiello M, Cogswell P, Clarke JB, Ting JP. CCAAT box binding protein NF-Y facilitates in vivo recruitment of upstream DNA binding transcription factors. Embo J. 1994 Sep;13(17):4042-4053. Pubmedid: 8076600. Pmcid: PMC395325.
  • Wright KL, Ting JP. In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma. Proc Natl Acad Sci U S A. 1992 Aug;89(16):7601-7605. Pubmedid: 1502171. Pmcid: PMC49758.
  • van Wijnen AJ, Choi TK, Owen TA, Wright KL, Lian JB, Jaenisch R, Stein JL, Stein GS. Involvement of the cell cycle-regulated nuclear factor HiNF-D in cell growth control of a human H4 histone gene during hepatic development in transgenic mice. Proc Natl Acad Sci U S A. 1991 Mar;88(6):2573-2577. Pubmedid: 2006193. Pmcid: PMC51275.
  • Owen TA, Bortell R, Yocum SA, Smock SL, Zhang M, Abate C, Shalhoub V, Aronin N, Wright KL, van Wijnen AJ. Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9990-9994. Pubmedid: 2124710. Pmcid: PMC55300.
  • McConnell HM, Wright KL, McFarland BG. The fraction of the lipid in a biological membrane that is in a fluid state: a spin label assay. Biochem Bioph Res Co. 1972 Apr;47(1):273-281. Pubmedid: 4337427.
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