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...
Although non-viral gene therapy has great potential for use in the lung, several problems including inefficient gene transfer and expression and the relative lack of cell-specific targeting have limited its applications. The two approaches that have been used to target genes to desired cell types are through specific ligand-receptor interactions...
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...
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 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...
Multiple Myeloma (MM) is an incurable plasma cell malignancy occurring within the bone marrow. Glucocorticoids (GCs) are widely used in the treatment of MM patients due to potent induction of apoptosis. Though known to occur via the glucocorticoid receptor (GR), the molecular details of GC-induced apoptosis in MM cells remain...
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...