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Faculty
Jaquelin Dudley
Professor of Molecular Genetics & Microbiology, Graduate Advisor

Email: jdudley@uts.cc.utexas.edu
Website
Main Office: NMS 2.122
Phone: (512) 471-8415

Alternate Office: NMS 2.262
Alt. Phone: (512) 471-5101

Mailing Address
The University of Texas at Austin
Section of Molecular Genetics and Microbiology
2505 Speedway Stop A5000
Austin ,TX 78712-1191
Jaquelin Dudley

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 funciton 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.