2006 Distinguished Research Career Award
Jaquelin P. Dudley, Professor of Molecular Genetics & Microbiology, University of Texas-Austin for her work on retroviral pathogenesis and control of gene expression.
Dr. Dudley has made key contributions to the understanding of retroviral pathogenesis, how cells achieve tissue-specific gene regulation, and molecular events that culminate in tumorigenesis. Using mouse mammary tumor virus (MMTV), Dr. Dudley has dissected a tightly controlled set of virus-host interactions that allow MMTV to exploit the immune system and specific transcription factors to sustain its complex life cycle. By genetic engineering experiments, Dr. Dudley has defined regions of the virus that switch MMTV-induced neoplasia in mice from mammary carcinomas to other tumor types, particularly T-cell lymphomas. In many years of research that continues today, Dr. Dudley has demonstrated the importance of the virally encoded superantigen gene for the virus life cycle and development of mammary cancer. Interestingly, she found that development of T-cell lymphomas was independent of superantigen expression and required both loss of negative regulatory elements and acquisition of enhancer activity to elevate MMTV expression in T cells, where mammotropic viruses are poorly expressed. To further characterize tissue-specific MMTV expression, Dr. Dudley identified two homeodomain-containing transcription factors, special AT-rich sequence binding protein (SATB1) and CCAAT-displacement protein (CDP/Cutl1). In a series of studies, she demonstrated that the repressor activity of these proteins in different tissues and developmental stages leads to extremely tight regulation of virus expression and allows optimal virus production only when MMTV is transmitted from mothers to offspring during lactation. Dr. Dudley's studies have also led to the discovery of a new MMTV export protein, Rem, which is functionally related to HIV Rev and HTLV Rex, but appears to have additional regulatory controls. Thus, MMTV embodies hallmark features of both genetically simple and complex retroviruses: tumorigenesis associated with MMTV insertions near cellular proto-oncogenes, such as c-myc, as well as coding capacity for multiple accessory proteins.
Dr. Dudley received the engraved crystal award sculpture and presented the special lecture "Gene regulation and cancer: lessons from mouse mammary tumor virus". Dr. Dudley also presented a "chalk talk" entitled "Manipulation of the immune response by MMTV" in April 2006 at the College of Veterinary Medicine on the campus of The Ohio State University.
Dr. Dudley's visit was sponsored jointly by the Center for Retrovirus Research and several OSU Departments of Veterinary Biosciences, and Molecular Virology, Immunology and Medical Genetics, as well as the Comprehensive Cancer Center Program in Viral Oncogenesis.
Dr. Jaquelin Dudley (right) receives Career Award crystal from Center for Retrovirus Research Associate Director, Dr. Kathleen Boris-Lawrie
Dr. Dudley during her distinguished seminar presentation to Center for Retrovirus Research and OSU faculty, students, and staff
Dr. Dudley presents a second lecture at the Retrovirus Center weekly Lab Meeting.