Desmosomes are adhesive complexes found at sites of intercellular contact that are essential for mediating cell-cell adhesion. These junctions undergo regulated assembly and reorganization during processes such as embryogenesis and wound healing. Plakophilins (PKPs) are armadillo family members related to the classic cadherin-associated protein p120ctn. PKPs localize to the cytoplasmic...
Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and in vivo. Although Lyn has been shown to be important in mediating LMP2A signaling, it is still unclear if Lyn is used preferentially or if...
Cardiovascular disease is a leading cause of morbidity and mortality worldwide. While many therapies have been used to treat vascular disease symptomatically, gene therapy offers a means of treating the molecular dysfunctions driving disease pathogenesis. Unfortunately, gene therapy has achieved only modest therapeutic success in clinical trials due to a...
Gonadotropins LH and FSH are secreted by the pituitary in response to hypothalamic GnRH and act to stimulate ovarian follicle development, steroid production and ovulation. Gonadal steroids, including estrogen, enter the circulation and provide neuroendocrine feedback at the hypothalamus and/or pituitary. Estrogen provides negative feedback to suppress gonadotropin release throughout...
PilD is an enzyme that processes prepilins that are part of the type II protein secretion apparatus and the type IV piliation machinery. Using a <em>Legionella pneumophila pilDlacZ</em> fusion strain to measure transcription, we observed a 20% increase in beta-galactosidase levels at 30°C vs. 37°C. At 25°C and 17°C vs....
Early-life seizures increase susceptibility to seizures in adulthood. However, mechanisms by which seizures in the developing brain lead to increased vulnerability to seizures and exacerbation of neurological injury in adulthood remain unknown. We test the hypothesis that upregulation of proinflammatory cytokine levels and chronic glial activation following early-life seizures result...
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,...
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...
Embryonic stem cells have the potential to differentiate into ectodermal, mesodermal and endodermal derivatives. This property makes them a valuable source of tissue specific progenitor and differentiated cells that can be used for cell replacement therapy. The first goal of this thesis is to test if cardiogenesis from embryonic stem...
The actions of luteinizing hormone (LH) to induce ovulation and luteinization of preovulatory follicles are mediated principally by activation of cAMP-dependent protein kinase (PKA) in granulosa cells. PKA activity is targeted to specific cellular locations by A-kinase anchoring proteins (AKAPs). I previously showed that follicle-stimulating hormone (FSH) induces expression of...