The primary function of the human urinary bladder is to store urine, while maintaining a permeability barrier that protects underlying tissues from noxious urinary components. Inflammatory diseases of the bladder, including urinary tract infection (UTI) and interstitial cystitis (IC), afflict millions of patients in the US annually and cause significant...
Most women diagnosed with epithelial ovarian carcinoma (EOC) initially present with metastases, but little is known about the regulation of ovarian tumor cell dissemination by the tumor microenvironment. Because ovarian cancer cell dissemination is mostly limited to the peritoneal cavity and often results in the accumulation of malignant ascites, the...
Arsenic trioxide (As<sub>2</sub>0<sub>3</sub>) is an arsenic-derivative that exhibits potent growth inhibitory effects against malignant cells. The remarkable antitumor effects of As<sub>2</sub>0<sub>3</sub> in vitro and in vivo have prompted the development of various clinical trials that established its activity in acute promyelocytic leukemia (APL). As<sub>2</sub>0<sub>3</sub> is part of the standard treatment...
><p><em>Vibrio cholerae</em>, the causative agent of the severe diarrheal disease cholera, secretes several "accessory" toxins including RTX toxin, which causes cross-linking of the actin cytoskeleton. The rtx locus of <em>V. cholerae</em> is located adjacent to the integrated CTX? prophage. The RTX toxin itself is encoded by the <em>rtxA</em> gene found...
There is increasing evidence that links chronic activation of glial cells and the subsequent self-propagating cycle of neuroinflammation to the neurodegenerative progression of Alzheimer's disease (AD). Nevertheless, attempts to identify currently approved drugs capable of safely attenuating the neuroinflammatory processes in AD have proven disappointing to date, and the development...
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...