Herpesviruses require axonal transport for the successful establishment of infection in peripheral ganglia (retrograde transport), and the subsequent spread to exposed body surfaces following reactivation from latency (anterograde transport). Viral progeny are assembled and spread to other tissues or hosts during egress. I focused on viral proteins which modulate directed...
The small heat shock protein αB-crystallin is expressed primarily in lens and muscle tissue, but it is also found in lung, kidney and many cancers. Regulators of αB-crystallin have been identified almost exclusively using mouse muscle and lens specific models. It has been well documented that αB-crystallin is expressed in...
Epstein Barr Virus (EBV) is associated with malignancies of lymphoid and epithelial origin. While the precise role of EBV in oncogenesis remains elusive, latent membrane protein 2A (LMP2A) is detected in all EBV-associated malignancies, implicating LMP2A in their pathogenesis. Interestingly, LMP2A is expressed in EBV-associated malignancies such as Burkitt's Lymphoma,...
Tonia René Holverson The HPV genome contains a bipartite promoter system that regulates the expression of early and late gene transcripts. The early proteins include the replication proteins E1 and E2, the oncoproteins E6 and E7, and the late functioning proteins E4 and E5. The late proteins include the capsid...
The kinetoplastid protozoan <em>Trypanosoma brucei</em> is the causative agent of African trypanosomiasis, affecting humans, and Nagana disease, affecting cattle, prevalent in regions of sub-Saharan Africa. Our lab demonstrated that the flagellum of <em>T. brucei</em> is enriched in lipid rafts, membrane areas composed of sphingolipids, sterols, and proteins that serve as...
Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients. However, the mechanisms controlling reactivation of latent CMV have not been understood. It is likely that reactivation is initiated by induction of IE gene expression. In this thesis, I studied molecular mechanisms leading to transcriptional activation of...
The Gram-negative bacterium <em> Vibrio cholerae </em> elicits disease through the export of enterotoxins. The <em> V. cholerae </em> RTX toxin was identified due its ability to cause cell rounding. Characterization of the RTX toxin demonstrated that this cell rounding was due to the depolymerization of the actin cytoskeleton through...
CD4-positive T cells express ligands for E- and P-selectins, carbohydrate-binding adhesion molecules that are induced on inflamed endothelium. The interaction between selectins and the selectin ligands facilitates the migration of T cells to sites of inflammation. The fucosyltransferase FucT-VII is essential for selectin ligand formation but the signaling and transcriptional...
Regulation of cell cycle and cell death are critical for normal cellular proliferation, tissue homeostasis, animal development, and the pathogenesis of human diseases such as cancer. Irregularities in cell cycle and cell death may result in tumorigenesis. In this dissertation, I describe my studies of a novel gene C53, which...
Arsenic trioxide exhibits potent antitumor effects in vitro and in vivo, and is widely used in the treatment of acute promyelocytic leukemia (APL) in humans. In addition to APL, arsenic is of potential therapeutic value for the treatment of other hematologic malignancies, including chronic myelogenous leukemia (CML). There is evidence...