Search

Your search keyword '"Mirza, Asra"' showing total 31 results
Start Over Author "Mirza, Asra"
31 results on '"Mirza, Asra"'

1. Development of a Cell-Based Reporter Potency Assay for Live Virus Vaccines.

Author

Sun, Dengyun, Meyer, Brian K., Deevi, Dhanvanthri S., Mirza, Asra, He, Li, Gruber, Ashley, Abbondanzo, Susan J., Benton, Noah A., Whiteman, Melissa C., Capen, Robert C., and Gurney, Kevin B.

Subjects
VIRAL vaccines, VESICULAR stomatitis, MEASLES virus, TISSUE culture, VIRUS diseases
Abstract

The rapid development of potency assays is critical in the development of life-saving vaccines. The traditional plaque assay or fifty percent tissue culture infectious dose (TCID50) assay used to measure the potency of live virus vaccines is time consuming, labor intensive, low throughput and with high variability. Described here is the development and qualification of a cell-based reporter potency assay for two vaccines for respiratory viral infection, one based on the recombinant vesicular stomatitis virus (rVSV) backbone, termed Vaccine 1 in this paper, and the other based on the measles virus vector, termed Vaccine 2. The reporter potency assay used a Vero E6 cell line engineered to constitutively express NanuLuc® luciferase, termed the VeroE6-NLuc or JM-1 cell line. Infection of JM-1 cells by a live virus, such as rVSV or measles virus, causes a cytopathic effect (CPE) and release of NanuLuc® from the cytoplasm into the supernatant, the amount of which reflects the intensity of the viral infection. The relative potency was calculated by comparison to a reference standard using parallel line analysis (PLA) in a log–log linear model. The reporter assay demonstrated good linearity, accuracy, and precision, and is therefore suitable for a vaccine potency assay. Further evaluation of the Vaccine 1 reporter assay demonstrated the robustness to a range of deliberate variation of the selected assay parameters and correlation with the plaque assay. In conclusion, we have demonstrated that the reporter assay using the JM-1 cell line could be used as a potency assay to support the manufacturing and release of multiple live virus vaccines. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

2. Discovery of sulfone containing metallo-β-lactamase inhibitors with reduced bacterial cell efflux and histamine release issues

Author

Bennett, Frank, Huang, Yuhua, Dong, Shuzhi, Jiang, Jinlong, Hunter, David, Zhao, Zhiqiang, Gu, Xin, Scott, Jack D., Tang, Haiqun, Yang, Dexi, Xiao, Li, Scapin, Giovanna, Fischmann, Thierry, Mirza, Asra, Dayananth, Priya, Painter, Ronald E., Villafania, Artjohn, Garlisi, Charles G., Zhang, Rumin, Mayhood, Todd W., Si, Qian, Li, Nianyu, Amin, Rupesh P., Chen, Feifei, Bhatt, Bhavana, Regan, Christopher P., Regan, Hilary, Lin, Xinjie, Wu, Jin, Leithead, Andrew, Young, Katherine, and Pasternak, Alexander

Published
2024
Full Text
View/download PDF

3. Structure Guided Discovery of Novel Pan Metallo-β-Lactamase Inhibitors with Improved Gram-Negative Bacterial Cell Penetration

Author

Dong, Shuzhi, Zhao, Zhiqiang, Tang, Haiqun, Li, Guoqing, Pan, Jianping, Gu, Xin, Jiang, Jinlong, Xiao, Li, Scapin, Giovanna, Hunter, David N., Yang, Dexi, Huang, Yuhua, Bennett, Frank, Yang, Shu-Wei, Mandal, Mihirbaran, Tang, Haifeng, Su, Jing, Tudge, Clare, deJesus, Reynalda Keh, Ding, Fa-Xiang, Lombardo, Matthew, Hicks, Jacqueline D., Fischmann, Thierry, Mirza, Asra, Dayananth, Priya, Painter, Ronald E., Villafania, Artjohn, Garlisi, Charles G., Zhang, Rumin, Mayhood, Todd W., Si, Qian, Li, Nianyu, Amin, Rupesh P., Bhatt, Bhavana, Chen, Feifei, Regan, Christopher P., Regan, Hillary, Lin, Xinjie, Wu, Jin, Leithead, Andrew, Pollack, Scott R., Scott, Jack D., Nargund, Ravi P., Therien, Alex G., Black, Todd, Young, Katherine, and Pasternak, Alexander

Abstract

The use of β-lactam (BL) and β-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-β-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.

Published
2024
Full Text
View/download PDF

4. Rapid Evolution of a Fragment-like Molecule to Pan-Metallo-Beta-Lactamase Inhibitors: Initial Leads toward Clinical Candidates

Author

Mandal, Mihirbaran, primary, Xiao, Li, additional, Pan, Weidong, additional, Scapin, Giovanna, additional, Li, Guoqing, additional, Tang, Haiqun, additional, Yang, Shu-Wei, additional, Pan, Jianping, additional, Root, Yuriko, additional, de Jesus, Reynalda Keh, additional, Yang, Christine, additional, Prosise, Winnie, additional, Dayananth, Priya, additional, Mirza, Asra, additional, Therien, Alex G., additional, Young, Katherine, additional, Flattery, Amy, additional, Garlisi, Charles, additional, Zhang, Rumin, additional, Chu, Donald, additional, Sheth, Payal, additional, Chu, Inhou, additional, Wu, Jin, additional, Markgraf, Carrie, additional, Kim, Hai-Young, additional, Painter, Ronald, additional, Mayhood, Todd W., additional, DiNunzio, Edward, additional, Wyss, Daniel F., additional, Buevich, Alexei V., additional, Fischmann, Thierry, additional, Pasternak, Alexander, additional, Dong, Shuzhi, additional, Hicks, Jacqueline D., additional, Villafania, Artjohn, additional, Liang, Lianzhu, additional, Murgolo, Nicholas, additional, Black, Todd, additional, Hagmann, William K., additional, Tata, Jim, additional, Parmee, Emma R., additional, Weber, Ann E., additional, Su, Jing, additional, and Tang, Haifeng, additional

Published
2022
Full Text
View/download PDF

10. The receptors DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing

Author

Jiang, Wanping, Swiggard, William J., Heufler, Christine, Peng, Michael, Mirza, Asra, Steinman, Ralph M., and Nussenzweig, Michael C.

Subjects
Major histocompatibility complex -- Observations, Epithelial cells -- Observations, Immunoglobulins -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Antigen-presentation factors of dendritic cells and thymic cells is associated with a high level expression of DEC-205. DEC is an integral membrane protein homologous to the macrophage mannose receptor and is capable of binding carbohydrates and mediate endocytosis. Test showed that the dendritic cells presented rabbit anti-DEC-205 to the T-cell clones two orders of magnitude more efficiently than the non-immune rabbit IgG-peptide. DEC-205 is rapidly taken up by means of coated pits and vesicles and delivered to a multivascular endosomal compartment that resembles the MHC class II-containing vesicles.

Published
1995

11. Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets

Author

Mann, Paul A., primary, Müller, Anna, additional, Wolff, Kerstin A., additional, Fischmann, Thierry, additional, Wang, Hao, additional, Reed, Patricia, additional, Hou, Yan, additional, Li, Wenjin, additional, Müller, Christa E., additional, Xiao, Jianying, additional, Murgolo, Nicholas, additional, Sher, Xinwei, additional, Mayhood, Todd, additional, Sheth, Payal R., additional, Mirza, Asra, additional, Labroli, Marc, additional, Xiao, Li, additional, McCoy, Mark, additional, Gill, Charles J., additional, Pinho, Mariana G., additional, Schneider, Tanja, additional, and Roemer, Terry, additional

Published
2016
Full Text
View/download PDF

12. Discovery of Novel 3,3-Disubstituted Piperidines as Orally Bioavailable, Potent, and Efficacious HDM2-p53 Inhibitors

Author

Bogen, Stéphane L., primary, Pan, Weidong, additional, Gibeau, Craig R., additional, Lahue, Brian R., additional, Ma, Yao, additional, Nair, Latha G., additional, Seigel, Elise, additional, Shipps, Gerald W., additional, Tian, Yuan, additional, Wang, Yaolin, additional, Lin, Yinghui, additional, Liu, Ming, additional, Liu, Suxing, additional, Mirza, Asra, additional, Wang, Xiaoying, additional, Lipari, Philip, additional, Seidel-Dugan, Cynthia, additional, Hicklin, Daniel J., additional, Bishop, W. Robert, additional, Rindgen, Diane, additional, Nomeir, Amin, additional, Prosise, Winifred, additional, Reichert, Paul, additional, Scapin, Giovanna, additional, Strickland, Corey, additional, and Doll, Ronald J., additional

Published
2016
Full Text
View/download PDF

13. Abstract 2785: Discovery of a novel HDM2 inhibitor with potent in vivo anti-tumor activity

Author

Wang, Yaolin, primary, Lipari, Philip, additional, Mirza, Asra, additional, Lin, Yinghui, additional, Zhang, Rumin, additional, Bogen, Stephane, additional, Ma, Yao, additional, Hicklin, Daniel J., additional, Seidel-Dugan, Cynthia, additional, Liu, Suxing, additional, Wang, Xiaoying, additional, Doll, Ronald, additional, Shipps, Gerald, additional, and Bishop, Walter Robert, additional

Published
2012
Full Text
View/download PDF

15. Abstract 4534: A novel and potent small molecule antagonist of HDM2, SCH 1450206, activates the p53 pathway with mechanism-based activity

Author

Liu, Suxing, primary, Mirza, Asra, additional, Wang, Xiaoying, additional, Lipari, Philip, additional, Lin, Yinghui, additional, Bogen, Stephane, additional, Ma, Yao, additional, Doll, Ronald, additional, Shipps, Gerald, additional, Seidel-Dugan, Cynthia, additional, Hicklin, Daniel J., additional, Bishop, W. Robert, additional, and Wang, Yaolin, additional

Published
2010
Full Text
View/download PDF

16. Abstract 4533: In vivo activation of the p53 pathway leading to tumor regression by a novel and potent HDM2 antagonist SCH 1450206

Author

Wang, Yaolin, primary, Wang, Xiaoying, additional, Lipari, Philip, additional, Ponery, Abdul-Samad, additional, Liu, Suxing, additional, Mirza, Asra, additional, Liu, Yinghui, additional, Bogen, Stephane, additional, Ma, Yao, additional, Doll, Ronald, additional, Shipps, Gerald, additional, Liu, Ming, additional, Seidel-Dugan, Cynthia, additional, Hicklin, Daniel J., additional, and Bishop, Walter Robert, additional

Published
2010
Full Text
View/download PDF

19. Integrative Genomics Revealed RAI3 Is a Cell Growth-promoting Gene and a Novel P53 Transcriptional Target

Author

Wu, Qun, primary, Ding, Wei, additional, Mirza, Asra, additional, Van Arsdale, Tish, additional, Wei, Iris, additional, Bishop, W. Robert, additional, Basso, Andrea, additional, McClanahan, Terri, additional, Luo, Lin, additional, Kirschmeier, Paul, additional, Gustafson, Eric, additional, Hernandez, Marco, additional, and Liu, Suxing, additional

Published
2005
Full Text
View/download PDF

22. Generation of p53 Target Database Via Integration of Microarray and Global p53 DNA-Binding Site Analysis.

Author

Walker, John M., Schönthal, Axel H., Liu, Suxing, Mirza, Asra, and Wang, Luquan

Abstract

The completion of the human genome sequence and availability of cDNA microarray technology provide new approaches to explore global cellular regulatory mechanisms. Here we present a strategy to identify genes regulated by specific transcription factors in the human genome, and apply it to p53. We first collected promoters or introns of all genes available using two methods: GenBank annotation and a computationally derived transcript map. The "FindPatterns" program is then used to search sequences in regulatory regions that match the p53 DNA-binding consensus sequence, resulting in the p53 Target Database. This database collects human genes that have at least one p53 DNA-binding sequence in their regulatory region. cDNA microarray was also used to identify genes that respond to p53 at a genomic scale. Integration of the microarray data and the p53 Target Database should greatly enrich direct p53 target genes. Taqman® analysis and quantitative chromatin immunoprecipitation analysis are used to validate the in silico prediction and microarray data. Enrichment factor analysis is used to demonstrate that in silico prediction greatly enriches for genes that are transcriptionally regulated by p53 and assists us to identify other signaling pathways that are potentially connected to p53. The approaches can be extended to other transcription factors. The methods shown here illustrate a novel approach to the analysis of global gene regulatory networks through the integration of human genomic sequence information and genome-wide gene expression analysis. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

29. Integrative Genomics Revealed RA13 Is a Cell Growth-promoting Gene and a Novel P53 Transcriptional Target.

Author

Qun Wu, Wei Ding, Mirza, Asra, van Arsdale, Tish, Wei, Iris, Bishop, W. Robert, Basso, Andrea, McClanahan, Terri, Lin Luo, Kirschmeier, Paul, Gustafson, Eric, Hernandez, Marco, and Suxing Liu

Subjects
*GROWTH factors, *GENE expression, *P53 antioncogene, *EPITHELIAL cells, *BREAST cancer, *CANCER cells, *CELL lines
Abstract

In this study, differential gene expression between normal human mammary epithelial cells and their malignant counterparts (eight well established breast cancer cell lines) was studied using Incyte GeneAlbum 1–6, which contains 65,873 eDNA clones representing 33,515 individual genes. 3,152 cDNAs showed a ≥3.0-fold expression level change in at least one of the human breast cancer cell lines as compared with normal human mammary epithelial cells. Integration of breast tumor gene expression data with the genes in the tumor suppressor p53 signaling pathway yielded 128 genes whose expression is altered in breast tumor cell lines and in response to p53 expression. A hierarchical cluster analysis of the 128 genes revealed that a significant portion of genes demonstrate an opposing expression pattern, i.e. p53-activated genes are down-regulated in the breast tumor lines, whereas p53-repressed genes are up-regulated. Most of these genes are involved in cell cycle regulation and/or apoptesis, consistent with the tumor suppresser function of p53. Follow-up studies on one gene, RAI3, suggested that p53 interacts with the promoter of RAI3 and repressed its expression at the onset of apoptosis. The expression of RAI3 is elevated in most tumor cell lines expressing mutant p53, whereas RAI3 mRNA is relatively repressed in the tumor cell lines expressing wild-type p53. Furthermore, ectopic expression of RAI3 in 293 cells promotes anchorage-independent growth and small interfering RNA-mediated depletion of RAI3 in AsPc-1 pancreatic tumor cells induces cell morphological change. Taken together, these data suggest a role for RAI3 in tumor growth and demonstrate the predictive power of integrative genomics. [ABSTRACT FROM AUTHOR]

Published
2005
Full Text
View/download PDF

30. Generation of p53 target database via integration of microarray and global p53 DNA-binding site analysis.

Author

Liu S, Mirza A, and Wang L

Subjects
Binding Sites, Chromatin, Female, Gene Expression Regulation, Genome, Human, Humans, Ovarian Neoplasms genetics, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Precipitin Tests methods, RNA, Messenger genetics, Regulatory Sequences, Nucleic Acid, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Computational Biology methods, DNA analysis, Gene Expression Profiling methods, Oligonucleotide Array Sequence Analysis methods, Tumor Suppressor Protein p53 genetics
Abstract

The completion of the human genome sequence and availability of cDNA microarray technology provide new approaches to explore global cellular regulatory mechanisms. Here we present a strategy to identify genes regulated by specific transcription factors in the human genome, and apply it to p53. We first collected promoters or introns of all genes available using two methods: GenBank annotation and a computationally derived transcript map. The "FindPatterns" program is then used to search sequences in regulatory regions that match the p53 DNA-binding consensus sequence, resulting in the p53 Target Database. This database collects human genes that have at least one p53 DNA-binding sequence in their regulatory region. cDNA microarray was also used to identify genes that respond to p53 at a genomic scale. Integration of the microarray data and the p53 Target Database should greatly enrich direct p53 target genes. Taqman analysis and quantitative chromatin immunoprecipitation analysis are used to validate the in silico prediction and microarray data. Enrichment factor analysis is used to demonstrate that in silico prediction greatly enriches for genes that are transcriptionally regulated by p53 and assists us to identify other signaling pathways that are potentially connected to p53. The approaches can be extended to other transcription factors. The methods shown here illustrate a novel approach to the analysis of global gene regulatory networks through the integration of human genomic sequence information and genome-wide gene expression analysis.

Published
2004
Full Text
View/download PDF

31. Transforming growth factor-beta 2 is a transcriptional target for Akt/protein kinase B via forkhead transcription factor.

Author

Samatar AA, Wang L, Mirza A, Koseoglu S, Liu S, and Kumar CC

Subjects
Base Sequence, Binding Sites, Cell Line, Chloramphenicol O-Acetyltransferase genetics, Consensus Sequence, Forkhead Transcription Factors, Gene Expression Regulation immunology, Genes, Reporter, Humans, Promoter Regions, Genetic, Proto-Oncogene Proteins c-akt, RNA, Messenger genetics, Transforming Growth Factor beta2, Tumor Cells, Cultured, Nuclear Proteins metabolism, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins metabolism, Transcription Factors metabolism, Transcription, Genetic, Transforming Growth Factor beta genetics
Abstract

Tumors evade cell death by constitutively activating cell survival pathways and suppressing intrinsic death machinery. Activation of cell survival pathways leads to transcriptional repression of genes associated with cell death and activation of ones promoting anti-apoptosis. Akt/protein kinase B phosphorylates forkhead transcription factors and prevents their nuclear localization, leading to repression of genes involved in apoptosis, such as Fas ligand (FasL). Using bioinformatic approaches, we have identified three consensus sequences for forkhead transcription factor binding in transforming growth factor beta2 (TGF-beta2) promoter. TGF-beta inhibits cell proliferation and induces apoptosis in many cell types, and acquisition of TGF-beta resistance is linked to tumorigenesis. In this study, we show that activated Akt down-regulates TGF-beta2 promoter, and sequences within the promoter that are related to consensus forkhead binding sites are necessary for repression. Forkhead factor FKHRL1 binds in vitro to the three consensus sequences and can activate TGF-beta2 promoter in normal and Akt-transformed cell lines. In human breast and pancreatic tumors, activated Akt expression correlated with down-regulation of TGF-beta 2 mRNA levels. A number of tumor cells expressing activated Akt were responsive to TGF-beta addition, indicating the presence of an intact TGF-beta-signaling pathway. These results suggest that repression of TGF-beta 2 promoter activity in cells expressing activated Akt may play a role in promoting tumorigenesis and escape from the growth-inhibitory and/or apoptotic effects of TGF-beta.

Published
2002
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results