Jaquelin P. Dudley

Dudley was a graduate student with Dr. Janet Butel at Baylor College of Medicine in Houston from 1973-78. After graduation she had two postdoctoral stints, one with Nobel laureate Harold Varmus at the University of California in San Francisco from 1978-80, followed by another with Dr. Rex Risser of the McArdle Laboratory for Cancer Research at the University of Wisconsin, Madison, from 1980-82. She joined the faculty of The University of Texas at Austin in 1983 as an Assistant Professor in the Department of Microbiology (later the Section of Molecular Genetics and Microbiology and now the Department of Molecular Biosciences). Dudley became an Associate Professor in 1989 and a Professor in 1996. She also served as a member of the Board of Directors for Gala Industries, Inc. from 1991-2003.

Mouse mammary tumor virus (MMTV) is a retrovirus that induces mammary carcinomas and T-cell lymphomas in mice by insertional mutagenesis. The Dudley lab 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. Their 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, the Dudley lab is in the process of developing vectors for gene therapy of breast cancer. Their 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 them to develop and test new vectors for safety and efficacy in mice. Their goal is to provide more specific and less toxic treatments for human breast cancer.