Julie Tubb
University of Washington
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Featured researches published by Julie Tubb.
Nature Medicine | 1999
Richard O. Snyder; Carol H. Miao; Leonard Meuse; Julie Tubb; Brian A. Donahue; Hui Feng Lin; Darrel W. Stafford; Salil Patel; Arthur R. Thompson; Timothy C. Nichols; Marjorie S. Read; Dwight A. Bellinger; Kenneth M. Brinkhous; Mark A. Kay
Hemophilia B, or factor IX deficiency, is an X-linked recessive disorder occurring in about 1 in 25,000 males. Affected individuals are at risk for spontaneous bleeding into many organs; treatment mainly consists of the transfusion of clotting factor concentrates prepared from human blood or recombinant sources after bleeding has started. Small- and large-animal models have been developed and/or characterized that closely mimic the human disease state. As a preclinical model for gene therapy, recombinant adeno-associated viral vectors containing the human or canine factor IX cDNAs were infused into the livers of murine and canine models of hemophilia B, respectively. There was no associated toxicity with infusion in either animal model. Constitutive expression of factor IX was observed, which resulted in the correction of the bleeding disorder over a period of over 17 months in mice. Mice with a steady-state concentration of 25% of the normal human level of factor IX had normal coagulation. In hemophilic dogs, a dose of rAAV that was approximately 1/10 per body weight that given to mice resulted in 1% of normal canine factor IX levels, the absence of inhibitors, and a sustained partial correction of the coagulation defect for at least 8 months.
Gene Therapy | 1997
David B. Schowalter; Julie Tubb; M. L. Liu; Christopher B. Wilson; Mark A. Kay
An E1a-deleted adenovirus vector constitutively expressing native adenovirus E3-gp19K (Ad.RSV-gp19K) was constructed in order to determine whether or not E3-gp19K mediated interference with antigen presentation would result in prolonged transgene expression in vivo. Cultured fibroblasts infected with Ad.RSV-gp19K produced a native size gp19K protein and had decreased cell surface levels of MHC I as shown by immunoprecipitation and flow cytometry. The congenic mouse strains Balb/b (H-2b MHC I with high gp19K affinity), Balb/k (H-2k MHC I with no gp19K affinity), and Balb/c (H-2d MHC I with moderate gp19K affinity) were chosen for in vivo experiments because of their range of gp19K affinities. Following transduction of mice from each strain with Ad.RSV-gp19K and Ad/RSV-hAAT (a reporter adenovirus), or Ad/RSV-cFIX (control adenovirus) and Ad/RSV-hAAT, the level and duration of serum hAAT protein were unrelated to gp19K protein expression. Evaluation of MHC I abundance on hepatocytes following in vivo transduction demonstrated that recombinant adenovirus rapidly increased the abundance of surface MHC I molecules on hepatocytes, and surface MHC I molecules were reduced earlier and to a greater extent following wild-type adenovirus infection compared with hepatocytes transduced with control or Ad.RSV-gp19K recombinant adenovirus. This difference in surface MHC I down-regulation may be related to the different promoters (RSV-LTR versus the native E3 promoter), and will be an important consideration in the development of newer generation adenovirus vectors designed to evade host immune responses.
Gene Therapy | 2005
M Fragkos; N P Anagnou; Julie Tubb; David W. Emery
The development of oncoretrovirus vectors for human γ-globin has been hampered by problems of low expression and gene silencing. In order to address these problems, we investigated an enhancer element identified from individuals with deletional hereditary persistence of fetal hemoglobin 2 (HPFH2), a genetic condition characterized by elevated levels of γ-globin in adults. Plasmid transfection studies in erythroid MEL (murine erythroleukemia) cells demonstrated the HPFH2 element could function synergistically with the β-globin locus control region to enhance the expression of an Aγ-globin gene with a truncated −382 bp promoter. A series of oncoretrovirus vectors were subsequently generated that contain an expression cassette for Aγ-globin linked to various combinations of the HPFH2 enhancer, the α-globin HS40 enhancer, and several versions of the promoter from Aγ-globin or β-globin. Expression analysis in transduced MEL cell clones revealed very high levels of promoter-autonomous silencing that was at least partially abrogated by the HPFH2 enhancer. The vector containing a combination of a −201 bp Aγ-globin gene promoter with the Greek HPFH −117 point mutation and both the HPFH2 and HS40 enhancers exhibited no signs of vector silencing and was expressed at 248±99% per copy of mouse α-globin (62% of total α-globin). This represents a significant improvement over previously reported oncoretrovirus vectors for Aγ-globin, and demonstrates the capacity of the HPFH2 enhancer to abrogate sequence-autonomous silencing of the Aγ-globin promoter in the context of a gene transfer vector.
BioTechniques | 2005
Julie Tubb; Amy C. Groth; Louis Leong; David W. Emery
The bacteriophage lambda recombination system is increasingly used for recombinant DNA applications that involve the frequent transfer of sequences into and between shuttle and reporter vectors. This approach bypasses the need for restriction endonucleases or ligases and, as such, is easily scalable and automated. However this system has not yet been tested for the ability to support the simultaneous introduction of donor fragments into two separate target sites of a single reporter plasmid. This attribute would greatly facilitate studies of cis-regulatory elements that only function in specific combinations, such as a class of regulatory elements known as chromatin insulators. With the goal of facilitating a screen for chromatin insulators, we sought to determine whether the commercially available MultiSite Gateway Technology recombination system could be used to simultaneously insert candidate insulator elements into two separate locations of a functional reporter plasmid. We show that this application is both highly efficient and specific, generating the desired recombination products nearly three quarters of the time without disrupting the specificity of the reporter system. As such, these studies establish a novel application of the MultiSite Gateway Technology for the generation of recombinant reporter plasmids where the constituent elements function in a combinatorial fashion.
Gene Therapy | 1995
Darlene Barr; Julie Tubb; Ferguson D; Scaria A; André Lieber; Christopher B. Wilson; James D. Perkins; Mark A. Kay
Proceedings of the National Academy of Sciences of the United States of America | 2000
David W. Emery; Evangelia Yannaki; Julie Tubb; George Stamatoyannopoulos
Human Gene Therapy | 2007
Mari Aker; Julie Tubb; Amy C. Groth; Anatoly Bukovsky; Adam C. Bell; Gary Felsenfeld; Hans Peter Kiem; George Stamatoyannopoulos; David W. Emery
Molecular Therapy | 2002
Evangelia Yannaki; Julie Tubb; Mari Aker; George Stamatoyannopoulos; David W. Emery
Blood Cells Molecules and Diseases | 2006
Tamon Nishino; Julie Tubb; David W. Emery
Molecular Therapy | 2006
Mari Aker; Julie Tubb; Daniel G. Miller; George Stamatoyannopoulos; David W. Emery