Jillian A. Bristol

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All eight human herpesviruses have a conserved herpesvirus protein kinase (CHPK) that is important for the lytic phase of the viral life cycle. In this study, we show that heat shock protein 90 (Hsp90) interacts directly with each of the eight CHPKs, and we demonstrate that an Hsp90 inhibitor drug, 17-dimethylaminoethylamino-17-demethoxygeldanamycin(More)
CCAAT/enhancer binding protein (C/EBP) transcription factors play essential roles in regulating an array of cellular processes, including differentiation, energy metabolism, and inflammation. In this report we demonstrate that both C/EBPalpha and C/EBPbeta activate the promoter driving transcription of the tumor necrosis factor receptor 1 (TNFR1). TNFR1 is(More)
Hemophilia A patients are typically treated by factor VIII (FVIII) protein replacement, an expensive therapy that induces FVIII-specific inhibitors in approximately 30% of patients with severe hemophilia. FVIII gene therapy has the potential to improve the current treatment protocols. In this report, we used a hemophilia A mouse model to compare the humoral(More)
Oncolytic adenoviruses are being tested as biological cancer therapeutics. Ar6pAE2fF (E2F vector) contains the E2F-1 promoter to regulate the expression of the E1a gene in cells with a disregulated retinoblastoma pathway. Ar6pAE2fmGmF (E2F-GM vector) includes the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene to enhance(More)
Oncolytic adenoviral vectors selectively replicate in and lyse human tumor cells, providing a promising means for targeted tumor destruction. However, oncolytic vectors have limited capacity for incorporation of additional genetic material that could encode therapeutic transgenes and/or transcriptional regulatory control elements to augment the efficacy(More)
BACKGROUND SYN-004 is an orally administered β-lactamase enzyme, designed to be given concurrently with certain intravenous β-lactam antibiotics like cephalosporins. SYN-004 is intended to degrade residual antibiotics excreted into the intestine as a result of hepatobiliary excretion and to prevent the disruption of the gut microbiome by these excess(More)
While much is known about adenovirus biology from its development as a therapeutic gene delivery vehicle, an important question remains regarding the appropriate in vivo vector dose. We describe here an in vivo dose threshold effect with an adenoviral vector expressing human Factor VIII (FVIII) in hemophiliac mice. Upon administration of vector doses(More)
Factor IX is synthesized in a precursor form with a propeptide that contains the gamma-carboxylation recognition site, an element which directs the post-translational gamma-carboxylation of adjacent glutamic acid residues. After protein synthesis, the propeptide is cleaved to yield the mature Factor IX. To study propeptide processing, anti-proFactor IX(More)
Prothrombin is a vitamin K-dependent blood coagulation protein that undergoes posttranslational gamma-carboxylation and propeptide cleavage during biosynthesis. The propeptide contains the gamma-carboxylation recognition site that directs gamma-carboxylation. To identify the intracellular sites of carboxylation and propeptide cleavage, we monitored the(More)
The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated(More)