Jaquelin Dudley

Dudley, Jaquelin
Professor of Molecular Genetics & Microbiology

E-mail: jdudley@uts.cc.utexas.edu

Website: http://www.biosci.utexas.edu/mgm/People/Faculty/profiles/?id=1528

Main Office: NMS 2.122
Phone: 471-8415

Alternate Office: NMS 2.262
Phone: 471-5101

Mailing Address:
The University of Texas at Austin
1 University Station A5000; NMS 2.104
Austin, TX 78712-0162

Graduate Students:

  • Ali, Almas
  • Byun, Hyewon

    • Post Doc Students:

  • Barnett, Anna
  • Bhadra, Sagar
  • Mertz, Jennifer
  • Mustafa, Farah

    • Research Summary:
       Mouse mammary tumor virus (MMTV) is a retrovirus that induces mammary carcinomas and T-cell lymphomas in mice by insertional mutagenesis. We have identified the Cux1 protein (also known as CCAAT-displacement protein, CDP, Cutl1 or Cux1) as a transcriptional repressor of MMTV expression. Developmentally programmed disappearance of the repressor, CDP, during lactation allows maximum virus expression during MMTV transmission from mothers to pups through the milk. We also have shown that Cux1 is important for expression of a number of mammary-specific genes. Most recently, Cux1 overexpression has been linked to poor prognosis for human breast cancer patients, and we have created Cux1-knockout mice to study mammary cancer progression in mouse models. These studies promise to increase our understanding of tissue-specific gene regulation and tumorigenesis. We also have been developing MMTV as a vector system for gene therapy of breast cancer. In this process, we discovered a new viral protein, Rem, which is involved in the nuclear export and expression of intron-containing viral mRNAs. These results are exciting because MMTV may be used as a mouse model for study of another retrovirus, human immunodeficiency virus (HIV), which causes AIDS. Finally, we are interested in studying the host response to viral and bacterial pathogens. We have developed a unique mouse strain called BALB/Mtv-null that is more than 99% identical to the inbred BALB/c mouse strain, but lack MMTV sequences in their germline. Unlike the parental BALB/c mice, Mtv-null mice are resistant to mammary tumors induced by MMTV, T-cell lymphomas induced by type B leukemogenic virus (TBLV), and death induced by infection with cholera-toxin producing strains of Vibrio cholera. Elucidation of the mechanism of this host resistance should allow us to develop novel methods for fighting different pathogenic organisms that might be used for bioterrorism.
     
    Research Images:

    MMTV life cycle - Mouse mammary tumor virus (MMTV) is a retrovirus that has a single-stranded RNA genome. Replication of the viral RNA by virally encoded reverse transcriptase gives a double-stranded DNA copy or provirus with long terminal repeats (LTRs). Integration of the provirus near cellular proto-oncogenes leads to changes in cellular gene expression and either mammary tumors or T-cell lymphomas. Large MMTV Life Cycle Image

     
    Publications:
    Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element (2009) Retrovirology 6
    BALB/Mtv-null mice responding to strong mouse mammary tumor virus superantigens restrict mammary tumorigenesis (2009) J. Virol. 83
    ALY is a common coactivator of RUNX1 and c-Myb on the type B leukemogenic virus enhancer (2007) J. Virol. 81, 3503-3513.
    Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens. (2006) PLoS Pathogens 2, e128.
    Differentiation-induced cleavage of Cutl1/CDP generates a novel dominant-negative isoform that regulates mammary gene expression (2006) Mol. Cell. Biol. 26, 7466-7478.
    Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus (2005) J. Virol. 79, 14737-14747.
    Conversion of mouse mammary tumor virus to a lymphomagenic virus (2005) J. Virol. 79, 12592-12596.
    Nuclear matrix binding regulates SATB1-mediated transcriptional repression (2005) J. Biol. Chem. 280, 24600-24609.
    Rory(Rorc) is a common integration site in type B leukemogenic virus-induced T-cell lymphomas. (2004) J. Virol. 78 , 4943-4946..
    The homeodomain protein CDP regulates mammary-specific gene transcription and tumorigenesis. (2004) Mol. Cell. Biol. 24, 4810-4823.
    Binding of CCAAT displacement protein CDP to adenovirus packaging sequences. (2003) J. Virol. 77 , 6255-6264..

     
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