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446 results on '"Narendran, Aru"'

1. Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing

Author

McAuley, Grace E, Yiu, Gloria, Chang, Patrick C, Newby, Gregory A, Campo-Fernandez, Beatriz, Fitz-Gibbon, Sorel T, Wu, Xiaomeng, Kang, Sung-Hae L, Garibay, Amber, Butler, Jeffrey, Christian, Valentina, Wong, Ryan L, Everette, Kelcee A, Azzun, Anthony, Gelfer, Hila, Seet, Christopher S, Narendran, Aru, Murguia-Favela, Luis, Romero, Zulema, Wright, Nicola, Liu, David R, Crooks, Gay M, and Kohn, Donald B

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Research, Rare Diseases, Genetics, Stem Cell Research, Biotechnology, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Transplantation, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Humans, Animals, Mice, T-Lymphocytes, Severe Combined Immunodeficiency, Gene Editing, Mice, SCID, CD3 Complex, Receptors, Antigen, T-Cell, CD3D severe combined immune deficiency, CITE-seq, artificial thymic organoid, base editing, hematopoietic stem and progenitor cells, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

CD3δ SCID is a devastating inborn error of immunity caused by mutations in CD3D, encoding the invariant CD3δ chain of the CD3/TCR complex necessary for normal thymopoiesis. We demonstrate an adenine base editing (ABE) strategy to restore CD3δ in autologous hematopoietic stem and progenitor cells (HSPCs). Delivery of mRNA encoding a laboratory-evolved ABE and guide RNA into a CD3δ SCID patient's HSPCs resulted in a 71.2% ± 7.85% (n = 3) correction of the pathogenic mutation. Edited HSPCs differentiated in artificial thymic organoids produced mature T cells exhibiting diverse TCR repertoires and TCR-dependent functions. Edited human HSPCs transplanted into immunodeficient mice showed 88% reversion of the CD3D defect in human CD34+ cells isolated from mouse bone marrow after 16 weeks, indicating correction of long-term repopulating HSCs. These findings demonstrate the preclinical efficacy of ABE in HSPCs for the treatment of CD3δ SCID, providing a foundation for the development of a one-time treatment for CD3δ SCID patients.

Published
2023

8. Tumour exosome integrins determine organotropic metastasis

Author

Hoshino, Ayuko, Costa-Silva, Bruno, Shen, Tang-Long, Rodrigues, Goncalo, Hashimoto, Ayako, Tesic Mark, Milica, Molina, Henrik, Kohsaka, Shinji, Di Giannatale, Angela, Ceder, Sophia, Singh, Swarnima, Williams, Caitlin, Soplop, Nadine, Uryu, Kunihiro, Pharmer, Lindsay, King, Tari, Bojmar, Linda, Davies, Alexander E, Ararso, Yonathan, Zhang, Tuo, Zhang, Haiying, Hernandez, Jonathan, Weiss, Joshua M, Dumont-Cole, Vanessa D, Kramer, Kimberly, Wexler, Leonard H, Narendran, Aru, Schwartz, Gary K, Healey, John H, Sandstrom, Per, Jørgen Labori, Knut, Kure, Elin H, Grandgenett, Paul M, Hollingsworth, Michael A, de Sousa, Maria, Kaur, Sukhwinder, Jain, Maneesh, Mallya, Kavita, Batra, Surinder K, Jarnagin, William R, Brady, Mary S, Fodstad, Oystein, Muller, Volkmar, Pantel, Klaus, Minn, Andy J, Bissell, Mina J, Garcia, Benjamin A, Kang, Yibin, Rajasekhar, Vinagolu K, Ghajar, Cyrus M, Matei, Irina, Peinado, Hector, Bromberg, Jacqueline, and Lyden, David

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Cancer, Rare Diseases, Lung, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Animals, Biomarkers, Brain, Cell Line, Tumor, Endothelial Cells, Epithelial Cells, Exosomes, Female, Fibroblasts, Genes, src, Humans, Integrin alpha6beta1, Integrin alpha6beta4, Integrin beta Chains, Integrin beta4, Integrins, Kupffer Cells, Liver, Mice, Mice, Inbred C57BL, Neoplasm Metastasis, Organ Specificity, Phosphorylation, Receptors, Vitronectin, S100 Proteins, Tropism, General Science & Technology
Abstract

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Published
2015

15. Supplementary Tables 1 - 5, Figures 1 - 6 from Personalizing the Treatment of Pediatric Medulloblastoma: Polo-like Kinase 1 as a Molecular Target in High-Risk Children

Author

Triscott, Joanna, primary, Lee, Cathy, primary, Foster, Colleen, primary, Manoranjan, Branavan, primary, Pambid, Mary Rose, primary, Berns, Rachel, primary, Fotovati, Abbas, primary, Venugopal, Chitra, primary, O'Halloran, Katrina, primary, Narendran, Aru, primary, Hawkins, Cynthia, primary, Ramaswamy, Vijay, primary, Bouffet, Eric, primary, Taylor, Michael D., primary, Singhal, Ash, primary, Hukin, Juliette, primary, Rassekh, Rod, primary, Yip, Stephen, primary, Northcott, Paul, primary, Singh, Sheila K., primary, Dunham, Christopher, primary, and Dunn, Sandra E., primary

Published
2023
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16. Supplementary Figure Legend from Personalizing the Treatment of Pediatric Medulloblastoma: Polo-like Kinase 1 as a Molecular Target in High-Risk Children

Author

Triscott, Joanna, primary, Lee, Cathy, primary, Foster, Colleen, primary, Manoranjan, Branavan, primary, Pambid, Mary Rose, primary, Berns, Rachel, primary, Fotovati, Abbas, primary, Venugopal, Chitra, primary, O'Halloran, Katrina, primary, Narendran, Aru, primary, Hawkins, Cynthia, primary, Ramaswamy, Vijay, primary, Bouffet, Eric, primary, Taylor, Michael D., primary, Singhal, Ash, primary, Hukin, Juliette, primary, Rassekh, Rod, primary, Yip, Stephen, primary, Northcott, Paul, primary, Singh, Sheila K., primary, Dunham, Christopher, primary, and Dunn, Sandra E., primary

Published
2023
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20. Preclinical Study of Enitociclib, a Selective CDK9 Inhibitor, in Combination with Bortezomib, Lenalidomide, Pomalidomide, or Venetoclax in the Treatment of Multiple Myeloma

Author

Tran, Son, primary, Sharma, Ritul, additional, Zhang, Chunfen, additional, Maity, Ranjan, additional, Johnson, Amy J., additional, Frigault, Melanie M., additional, Izumi, Raquel, additional, Hamdy, Ahmed, additional, Stelte-Ludwig, Beatrix, additional, Bahlis, Nizar J., additional, Neri, Paola, additional, and Narendran, Aru, additional

Published
2022
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