DUDLEY, JAQUELIN P

Jaquelin P Dudley

Professor
Molecular Biosciences


Molecular biology and pathogenesis of retroviruses

jdudley@austin.utexas.edu

Phone: 512-471-8415

Office Location
NMS 2.122

Postal Address
100 E. 24th Street Stop A5000
Austin, TX 78712
1973-78   Graduate student with Dr. Janet Butel, Baylor College of Medicine, Houston, TX
1978-80   Postdoctoral fellow with Nobel laureate Harold Varmus, University of California, San Francisco, CA
1980-82   Postdoctoral fellow with Dr. Rex Risser, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI
1983-89   Assistant Professor, Dept. of Microbiology, University of Texas at Austin, Austin, TX

1989-96

 

Associate Professor, Dept. of Microbiology, University of Texas at Austin, Austin, TX

1991-03  

Member, Board of Directors, Gala Industries, Inc.

1996-   Professor, Dept. of Microbiology, University of Texas at Austin, Austin, TX

 

 

 

 

 

 

 

   

   

   

   

   

   

       

 

Research Summary:

Mouse mammary tumor virus (MMTV) is a retrovirus that induces mammary carcinomas and T-cell lymphomas in mice by insertional mutagenesis. We recently discovered a novel viral protein, Rem, which is involved in the nuclear export and expression of intron-containing viral mRNAs. These results are exciting because MMTV serves as a mouse model for study of another retrovirus, human immunodeficiency virus (HIV), which causes AIDS. Our recent results suggest that Rem has a very unusual trafficking pattern within mammalian cells. Prior to nuclear entry, Rem appears to enter the endoplasmic reticulum (ER), where it is partially glycosylated, and cleaved by signal peptidase. Cleavage appears to yield an HIV Rev-like gene product, SP, as well as a unique product (Rem-CT) of unknown function. Mutations that prevent the correct processing and glycosylation of Rem interfere with SP activity in reporter assays. Rem trafficking through the ER is required for Rem processing and function in the nucleus after signal peptidase cleavage and retrotranslocation of the N-terminal SP out of the ER. Retrotranslocation is associated with endoplasmic reticulum-associated degradation (ERAD). ERAD is a poorly understood cellular process that is responsible for disposal of misfolded proteins. Numerous human diseases, including cancer and neurogeneration, show defects in ERAD. Recent exciting data indicate that the Rem C-terminus has a separate function in intrinsic immunity. Finally, we are in the process of developing vectors for gene therapy of breast cancer. Our studies have allowed the extensive mapping of the MMTV genome, which has been evolutionarily selected for optimal expression in the mammary gland. Elimination of viral genes, introduction of reporter genes, and manipulation of tissue-specific promoter elements should enable us to develop and test new vectors for safety and efficacy in mice. Our goal is to provide more specific and less toxic treatments for human breast cancer.

Publications:
2013 Myers L, Joedicke JJ, Carmody AB, Messer RJ, Kassiotis G, Dudley JP, Dittmer U, Hasenkrug KJ, IL-2-independent and TNF-α-dependent expansion of Vβ5+ natural regulatory T cells during retrovirus infection., J. Immunol. 190: 5485-5495 view

2012 Byun H, Halani N, Gou Y, Nash AK, Lozano MM, Dudley JP, Requirements for mouse mammary tumor virus Rem signal peptide processing and function, J. Virol. 86: 214-225 view

2011 Punkosdy, G. A., M. Blain, M. M. Lozano, J. P. Dudley, R. Ahmed, and E. M. Shevach, Foxp3+ regulatory T cells expand in response to endogenous retroviral superantigens during chronic viral infection, Proc. Natl. Acad. Sci. USA 108: 3677-3682 view

2010 Kozak, C., J. A. Mertz, S. Bhadra, M. Palmarini, and J. P. Dudley, Endogenous retroviruses and cancer, In J. P. Dudley (ed.) Retroviruses and Insights into Cancer, Springer, in press

2010 Byun, H., N. Halani, J. A. Mertz, A. F. Ali, M. M. Lozano, and J. P. Dudley, Retroviral Rem protein requires processing by signal peptidase and retrotranslocation for nuclear function, Proc. Natl. Acad. Sci. USA 107: 12287-12292 view

2009 Mertz, J. A., A. Chadee, H. Byun, R. Russell, and J. P. Dudley, Mapping of the functional boundaries and secondary structure of the mouse mammary tumor virus Rem-responsive element, J. Biol. Chem. 284: 25642-25652 view

2009 Mertz, J. A., M. M. Lozano, and J. P. Dudley. , Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element, Retrovirology 6: 10 view

2006 Bhadra, S., M. M. Lozano, S. M. Payne, and J. P. Dudley., Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens., PLoS Pathogens 2: e128 view

2006 Maitra, U., J. Seo, M. M. Lozano, and J. P. Dudley, Differentiation-induced cleavage of Cutl1/CDP generates a novel dominant-negative isoform that regulates mammary gene expression, Mol. Cell. Biol. 26: 7466-7478 view

 1984   

 

Selected for inclusion in the 1984 Esquire Magazine Register of "Outstanding Americans Under Age 40"

2006

  Recipient of the Ohio State University Center for Retrovirus Research Distinguished Research Career Award

2006

  Co-organizer of the Cold Spring Meeting on Retroviruses

2006

  Co-organizer of the West Coast Retrovirus Meeting

2007-present 

  Editorial Board, Journal of Virology

2007-present

  Editorial Board, The Open Virology Journal

2007

  Molecular Genetics and Microbiology Teaching Excellence Award

2007

  College of Natural Sciences Teaching Excellence Award

2008-present

  Editorial Board, Advances in Virology

2009

  Elected Fellow, American Academy of Microbiology

2010-present 

  Editorial Board, Virology

 

   

Advanced Virology (BIO391P)

Animal Virology (BIO330)

Training for both graduate and undergraduate students is available.