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...
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...
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...
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...
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...
Epstein-Barr virus (EBV) is a human gamma-herpesvirus that primarily infects B cells and epithelial cells. While the glycoproteins required for entry into these two cell types differ, the gH/gL glycoprotein complex is essential for entry into both epithelial and B cells. Analysis of gH protein sequences from three gamma-herpesviruses: EBV,...
The ubiquitin-proteasome system degrades regulatory proteins and thereby controls a broad range of cellular processes such as the cell cycle, DNA-repair, gene transcription and signal transduction. The proteasome typically degrades its substrates completely into small peptides. However, biological exceptions do occur. For example, the activity of a handful of transcriptional...
Initial studies described the ability of CD4+CD25+ T regulatory (Treg) cells in suppressing autoimmune diseases in animal models. An emerging interest has focused on the potential role of Treg cells in cancer development and progression as they have been shown to suppress anti-tumor immunity. In the present study, CD4+CD25- T...
The response to reduced levels of oxygen (hypoxia) is essential for embryonic development by promoting the proper formation of vascular networks. Conversely, hypoxia also promotes the development of pathophysiological processes such as pulmonary hypertension and cancer. The main mediator of responses to hypoxia within the cell is the transcription factor...
HspB2 was discovered as a chaperone of muscular dystrophy protein kinase (DMPK) and originally named, DMPK binding protein (MKBP) and presently called HspB2. Functionally, MKBP binds to DMPK and stabilizes its kinase activity, thereby accelerating the progression of muscular dystrophy. Although other binding partners of HspB2 have been found, the...