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Your search keyword '"Garcia-Blanco, Mariano"' showing total 23 results
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23 results on '"Garcia-Blanco, Mariano"'

1. Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine

Author

Kuzmin, Ivan V., Soto Acosta, Ruben, Pruitt, Layne, Wasdin, Perry T., Kedarinath, Kritika, Hernandez, Keziah R., Gonzales, Kristyn A., Hill, Kharighan, Weidner, Nicole G., Mire, Chad, Engdahl, Taylor B., Moon, Woohyun J., Popov, Vsevolod, Crowe, Jr, James E., Georgiev, Ivelin S., Garcia-Blanco, Mariano A., Abbott, Robert K., and Bukreyev, Alexander

Published
2024
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2. Definition of germ layer cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate.

Author

Fagg, W, Liu, Naiyou, Braunschweig, Ulrich, Pereira de Castro, Karen, Chen, Xiaoting, Ditmars, Frederick, Widen, Steven, Donohue, John, Modis, Katalin, Russell, William, Fair, Jeffrey, Weirauch, Matthew, Blencowe, Benjamin, and Garcia-Blanco, Mariano

Subjects
Alternative Splicing, Cell Differentiation, Cell Lineage, Endoderm, Germ Layers, Heart, Humans, Mesoderm, RNA-Binding Proteins
Abstract

Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 in BIN1 pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.

Published
2022

6. Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms

Author

Bukreyev, Alexander, primary, Kuzmin, Ivan, additional, Acosta, Ruben Soto, additional, Wasdin, Perry, additional, Mire, Chad, additional, Engdahl, Taylor, additional, Moon, Woohyun, additional, Popov, Vsevolod, additional, Crowe, James, additional, Georgiev, Ivelin, additional, Garcia-Blanco, Mariano, additional, and Abbott, Robert, additional

Published
2023
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8. The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

Author

Hirano, Minato, primary, Galarza-Muñoz, Gaddiel, primary, Nagasawa, Chloe, additional, Schott, Geraldine, additional, Wang, Liuyang, additional, Antonia, Alejandro L, additional, Jain, Vaibhav, additional, Yu, Xiaoying, additional, Widen, Steven G, additional, Briggs, Farren BS, additional, Gregory, Simon G, additional, Ko, Dennis C, additional, Fagg, William S, additional, Bradrick, Shelton, additional, and Garcia-Blanco, Mariano A, additional

Published
2023
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9. Supplemental Figure 1 from Development of a Novel c-MET–Based CTC Detection Platform

Author

Zhang, Tian, primary, Boominathan, Rengasamy, primary, Foulk, Brad, primary, Rao, Chandra, primary, Kemeny, Gabor, primary, Strickler, John H., primary, Abbruzzese, James L., primary, Harrison, Michael R., primary, Hsu, David S., primary, Healy, Patrick, primary, Li, Jing, primary, Pi, Cinthia, primary, Prendergast, Katherine M., primary, Hobbs, Carey, primary, Gemberling, Sarah, primary, George, Daniel J., primary, Hurwitz, Herbert I., primary, Connelly, Mark, primary, Garcia-Blanco, Mariano A., primary, and Armstrong, Andrew J., primary

Published
2023
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10. Data from Development of a Novel c-MET–Based CTC Detection Platform

Author

Zhang, Tian, primary, Boominathan, Rengasamy, primary, Foulk, Brad, primary, Rao, Chandra, primary, Kemeny, Gabor, primary, Strickler, John H., primary, Abbruzzese, James L., primary, Harrison, Michael R., primary, Hsu, David S., primary, Healy, Patrick, primary, Li, Jing, primary, Pi, Cinthia, primary, Prendergast, Katherine M., primary, Hobbs, Carey, primary, Gemberling, Sarah, primary, George, Daniel J., primary, Hurwitz, Herbert I., primary, Connelly, Mark, primary, Garcia-Blanco, Mariano A., primary, and Armstrong, Andrew J., primary

Published
2023
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12. Supplemental Figure 2 from Development of a Novel c-MET–Based CTC Detection Platform

Author

Zhang, Tian, primary, Boominathan, Rengasamy, primary, Foulk, Brad, primary, Rao, Chandra, primary, Kemeny, Gabor, primary, Strickler, John H., primary, Abbruzzese, James L., primary, Harrison, Michael R., primary, Hsu, David S., primary, Healy, Patrick, primary, Li, Jing, primary, Pi, Cinthia, primary, Prendergast, Katherine M., primary, Hobbs, Carey, primary, Gemberling, Sarah, primary, George, Daniel J., primary, Hurwitz, Herbert I., primary, Connelly, Mark, primary, Garcia-Blanco, Mariano A., primary, and Armstrong, Andrew J., primary

Published
2023
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13. Supplementary Tables 1-4, Figures 1-4 from Circulating Tumor Cells from Patients with Advanced Prostate and Breast Cancer Display Both Epithelial and Mesenchymal Markers

Author

Armstrong, Andrew J., primary, Marengo, Matthew S., primary, Oltean, Sebastian, primary, Kemeny, Gabor, primary, Bitting, Rhonda L., primary, Turnbull, James D., primary, Herold, Christina I., primary, Marcom, Paul K., primary, George, Daniel J., primary, and Garcia-Blanco, Mariano A., primary

Published
2023
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14. The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity

Author

Yeh, Shih-Chia, primary, Strilets, Tania, additional, Tan, Wei-Lian, additional, Castillo, David, additional, Medkour, Hacène, additional, Rey-Cadilhac, Félix, additional, Serrato-Pomar, Idalba M., additional, Rachenne, Florian, additional, Chowdhury, Avisha, additional, Chuo, Vanessa, additional, Azar, Sasha R., additional, Singh, Moirangthem Kiran, additional, Hamel, Rodolphe, additional, Missé, Dorothée, additional, Kini, R. Manjunatha, additional, Kenney, Linda J., additional, Vasilakis, Nikos, additional, Marti-Renom, Marc A., additional, Nir, Guy, additional, Pompon, Julien, additional, and Garcia-Blanco, Mariano A., additional

Published
2023
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15. Inefficient recruitment of DDX39B impedes pre-spliceosome assembly on FOXP3introns

Author

Nagasawa, Chloe K., Bailey, Aaron O., Russell, William K., and Garcia-Blanco, Mariano A.

Abstract

Forkhead box P3 (FOXP3) is the master fate-determining transcription factor in regulatory T (Treg) cells and is essential for their development, function, and homeostasis. Mutations in FOXP3cause immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, and aberrant expression of FOXP3has been implicated in other diseases such as multiple sclerosis and cancer. We previously demonstrated that pre-mRNA splicing of FOXP3RNAs is highly sensitive to levels of DExD-box polypeptide 39B (DDX39B), and here we investigate the mechanism of this sensitivity. FOXP3introns have cytidine (C)-rich/uridine (U)-poor polypyrimidine (py) tracts that are responsible for their inefficient splicing and confer sensitivity to DDX39B. We show that there is a deficiency in the assembly of commitment complexes (CCs) on FOXP3introns, which is consistent with the lower affinity of U2AF2 for C-rich/U-poor py tracts. Our data indicate an even stronger effect on the conversion of CCs to pre-spliceosomes. We propose that this is due to an altered conformation that U2AF2 adopts when it binds to C-rich/U-poor py tracts and that this conformation has a lower affinity for DDX39B. As a consequence, CCs assembled on FOXP3introns are defective in recruiting DDX39B, and this leads to the inefficient assembly of pre-spliceosome complexes.

Published
2024
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21. The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

Author

Hirano, Minato, primary, Galarza-Muñoz, Gaddiel, additional, Schott, Geraldine, additional, Wang, Liuyang, additional, Nagasawa, Chloe, additional, Antonia, Alejandro L., additional, Jain, Vaibhav, additional, Yu, Xiaoying, additional, Widen, Steven G, additional, Briggs, Farren BS, additional, Gregory, Simon G, additional, Ko, Dennis C., additional, Fagg, William S, additional, Bradrick, Shelton, additional, and Garcia-Blanco, Mariano A., additional

Published
2022
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22. Antisense modulation of IL7R splicing to control sIL7R expression in human CD4+T cells

Author

Galarza-Muñoz, Gaddiel, Kennedy-Boone, Debbie, Schott, Geraldine, Bradrick, Shelton S., and Garcia-Blanco, Mariano A.

Abstract

The interleukin 7 receptor (IL7R) is strongly associated with increased risk to develop multiple sclerosis (MS), an autoimmune disease of the central nervous system, and this association is likely driven by up-regulation of the soluble isoform of IL7R (sIL7R). Expression of sIL7R is determined by exclusion of the alternative exon 6 from IL7R transcripts, and our previous work revealed that the MS risk allele of the SNP rs6897932 within this exon enhances the expression of sIL7R by promoting exclusion of exon 6. sIL7R potentiates the activity of IL7, leading to enhanced expansion of T cells and increased disability in the experimental autoimmune encephalomyelitis (EAE) murine model of MS. This role in modulating T cell-driven immunity positions sIL7R as an attractive therapeutic target whose expression could be reduced for treatment of MS or increased for treatment of cancers. In this study, we identified novel antisense oligonucleotides (ASOs) that effectively control the inclusion (anti-sIL7R ASOs) or exclusion (pro-sIL7R ASOs) of this exon in a dose-dependent fashion. These ASOs provided excellent control of exon 6 splicing and sIL7R secretion in human primary CD4+T cells. Supporting their potential for therapeutic targeting, we showed that lead anti-sIL7R ASOs correct the enhanced exon 6 exclusion imposed by the MS risk allele of rs6897932, whereas lead pro-sIL7R ASOs phenocopy it. The data presented here form the foundation for future preclinical studies that will test the therapeutic potential of these ASOs in MS and immuno-oncology.

Published
2022
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23. Antisense modulation of IL7R splicing to control sIL7R expression in human CD4 + T cells.

Author

Galarza-Muñoz G, Kennedy-Boone D, Schott G, Bradrick SS, and Garcia-Blanco MA

Subjects
Animals, Exons, Humans, Mice, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense pharmacology, RNA Splicing, T-Lymphocytes, CD4-Positive T-Lymphocytes, Multiple Sclerosis genetics, Receptors, Interleukin-7 genetics
Abstract

The interleukin 7 receptor ( IL7R ) is strongly associated with increased risk to develop multiple sclerosis (MS), an autoimmune disease of the central nervous system, and this association is likely driven by up-regulation of the soluble isoform of IL7R (sIL7R). Expression of sIL7R is determined by exclusion of the alternative exon 6 from IL7R transcripts, and our previous work revealed that the MS risk allele of the SNP rs6897932 within this exon enhances the expression of sIL7R by promoting exclusion of exon 6. sIL7R potentiates the activity of IL7, leading to enhanced expansion of T cells and increased disability in the experimental autoimmune encephalomyelitis (EAE) murine model of MS. This role in modulating T cell-driven immunity positions sIL7R as an attractive therapeutic target whose expression could be reduced for treatment of MS or increased for treatment of cancers. In this study, we identified novel antisense oligonucleotides (ASOs) that effectively control the inclusion (anti-sIL7R ASOs) or exclusion (pro-sIL7R ASOs) of this exon in a dose-dependent fashion. These ASOs provided excellent control of exon 6 splicing and sIL7R secretion in human primary CD4 + T cells. Supporting their potential for therapeutic targeting, we showed that lead anti-sIL7R ASOs correct the enhanced exon 6 exclusion imposed by the MS risk allele of rs6897932, whereas lead pro-sIL7R ASOs phenocopy it. The data presented here form the foundation for future preclinical studies that will test the therapeutic potential of these ASOs in MS and immuno-oncology., (© 2022 Galarza-Muñoz et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Published
2022
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