Inactivation of tumor suppressors genes, which encode regulatory proteins critical for maintaining normal cellular function, is a common occurrence in cancer. Ikaros is a hematopoietic-specific zinc finger protein that functions as a differentiation regulator and has properties of a tumor suppressor. Ikaros functions to regulate gene expression as a component...
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...
Breast cancer cells acquire many genetic alterations in apoptotic signaling pathways rendering them resistant to apoptosis. Human Epidermal growth factor Receptor-2 (HER-2/ErbB2/neu) is amplified or overexpressed in approximately 30% of breast and ovarian tumors and correlates with poor prognosis. Although HER-2 is an orphan receptor, it forms potent signaling heterodimers...
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....
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...
PRC is a PGC-1 coactivator family member responsive to serum growth factors and up regulated in proliferating cells. Unlike PGC-1α and PGC-1β, PRC has not been studied extensively and and its function or regulation remains largely unknown. Both PGC-1α and PGC-1β have been shown to be important regulators of mitochondrial...
Early Growth Response genes (Egr1-4) are transcriptional mediators of signals governing growth and differentiation. In sympathetic neuron-derived cell lines, Egr1 is induced by NGF signaling, which is required for sympathetic neuron survival, differentiation and target organ innervation. In the absence of identifiable sympathetic defects in Egr1-deficient mice, we investigated the...
Fusion of biological membranes is dictated by the interaction between specialized membrane proteins and the lipid bilayer. Parainfluenza virus 5 (PIV5) mediates fusion using two surface glycoproteins: the fusion protein (F) and the attachment protein hemagglutinin-neuraminidase (HN). Activation of membrane fusion of PIV5 typically occurs at neutral pH, and involves...
TGF-β has been named the molecular Jekyll and Hyde of cancer due to its ability to both suppress and promote tumor development. Components of the TGF-β signaling pathway are often mutated in cancer to inhibit the tumor suppressor roles of TGF-β. Our lab studies how a 3-alanine deletion in the...