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...
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...
The cause(s) of Aβ overproduction and accumulation in SAD are unknown; however, several lines of evidence indicate that impaired energy metabolism in the brain may be involved. Furthermore, the rate-limiting enzyme in Aβ production, BACE1, is elevated in SAD brains around amyloid plaques, indicating that BACE1 may also play a...
Mechanisms of RNA Mediated Silencing in S. pombe Christina A. Lawrence Heterochromatin of eukaryotic genomes has classically been defined as condensed chromatin that is repressive to transcription and typically resides at highly repetitive regions of the genome. Genetic and molecular analyses have demonstrated that these regions are essential for genome...
Epstein-Barr virus (EBV) is a human herpesvirus that is able to infect both epithelial cells as well as B lymphocytes, where the virus stablishes life-long latency in the host. Five glycoproteins are involved in infection of B cells: gp350/220 for initial tethering of the virus to the cell via CD21,...
The T-box transcription factor, Tbx5, is involved in heart development and congenital disease. For example mutations in human TBX5 lead to Holt-Oram syndrome, a disease characterized by a range of heart and arm malformations. Tbx5 gene activity has been perturbed in several animal models including the chicken, mouse, and zebrafish....
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...
Herpes simplex virus (HSV) infection of host cells requires virus attachment to the cell surface and subsequent membrane fusion between the virus envelope and host cell membrane to deliver the nucleocapsid containing the viral genome into the host cell. A proposed mechanism for HSV glycoprotein-induced membrane fusion is gD binding...
Chagas heart disease, caused by infection with the protozoan parasite Trypanosoma cruzi, is still regarded as a major public health problem in Central and South America. The finding of cardiac specific autoimmunity during infection in both humans and experimental animals has provided a basis for investigation of its potential role...
Phagocytosis is an essential mechanism for clearance of pathogens, dying cells, and other unwanted debris in order to maintain tissue health in the body. Macrophages execute this process in the peripheral immune system, but in the brain microglia act as resident macrophages to accomplish this function. In the peripheral immune...
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...
Kinesin-1 is a motor protein that transports cargo along microtubules. Inside cells, the majority of kinesin-1 is regulated to conserve ATP and ensure its proper intracellular distribution and coordination with other motors. Regulated kinesin-1 is folded in half, and interactions between coiled-coil regions near the N-terminal enzymatically active heads and...
A tetramer model for HIV-1 Integrase (IN) with DNA representing the LTR termini was previously assembled which predicted amino acid residues on the enzyme surface that interact with the LTR termini (Chen et al, 2006). A separate structural alignment of HIV-1, SIV, and ASV INs predicted which of these residues...
The orderly process of hematopoietic differentiation is governed in large part by the coordinated transcription of specific genes. Deregulation of normal differentiation processes can lead to disease states including immunodeficiency, autoimmune disease, and leukemia. This research focuses on the family of transcription factors known as the early growth response (Egr)...