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466 results on '"Ngan, Bo"'

1. Single-cell transcriptomics of pediatric Burkitt lymphoma reveals intra-tumor heterogeneity and markers of therapy resistance: LYMPHOMA

Author

Corinaldesi, Clarissa, Holmes, Antony B., Martire, Gaia, Tosato, Anna, Rizzato, Domenico, Lovisa, Federica, Gallingani, Ilaria, Shen, Qiong, Ferrone, Lavinia, Harris, Marian, Davies, Kimberly, Molinaro, Luca, Mortara, Umberto, Dei Tos, Angelo Paolo, Ofori, Kenneth, D’Amore, Emanuele S. G., Chiarle, Roberto, Ngan, Bo, Carraro, Elisa, Pillon, Marta, Hussein, Shafinaz, Bhagat, Govind, Pizzi, Marco, Mussolin, Lara, and Basso, Katia

Published
2025
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2. NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity.

Author

Sharfe, Nigel, Dalal, Ilan, Naghdi, Zahra, Lefaudeux, Diane, Vong, Linda, Dadi, Harjit, Navarro, Hector, Tasher, Diana, Ovadia, Adi, Zangen, Tzili, Ater, Dorit, Ngan, Bo, Hoffmann, Alexander, and Roifman, Chaim

Subjects
Autoimmunity, Combined immunodeficiency, Memory B cells, NFκB pathway, Naïve T cells, RelB, Humans, Transcription Factor RelB, NF-kappa B, Signal Transduction, Gene Expression Regulation, Autoimmune Diseases
Abstract

BACKGROUND: Genetic aberrations in the NFκB pathway lead to primary immunodeficiencies with various degrees of severity. We previously demonstrated that complete ablation of the RelB transcription factor, a key component of the alternative pathway, results in an early manifested combined immunodeficiency requiring stem cell transplantation. OBJECTIVE: To study the molecular basis of a progressive severe autoimmunity and immunodeficiency in three patients. METHODS: Whole exome sequencing was performed to identify the genetic defect. Molecular and cellular techniques were utilized to assess the variant impact on NFκB signaling, canonical and alternative pathway crosstalk, as well as the resultant effects on immune function. RESULTS: Patients presented with multiple autoimmune progressive severe manifestations encompassing the liver, gut, lung, and skin, becoming debilitating in the second decade of life. This was accompanied by a deterioration of the immune system, demonstrating an age-related decline in naïve T cells and responses to mitogens, accompanied by a gradual loss of all circulating CD19+ cells. Whole exome sequencing identified a novel homozygous c. C1091T (P364L) transition in RELB. The P364L RelB protein was unstable, with extremely low expression, but retained some function and could be transiently and partially upregulated following Toll-like receptor stimulation. Stimulation of P364L patient fibroblasts resulted in a marked rise in a cluster of pro-inflammatory hyper-expressed transcripts consistent with the removal of RelB inhibitory effect on RelA function. This is likely the main driver of autoimmune manifestations in these patients. CONCLUSION: Incomplete loss of RelB provided a unique opportunity to gain insights into NFκBs pathway interactions as well as the pathogenesis of autoimmunity. The P364L RelB mutation leads to gradual decline in immune function with progression of severe debilitating autoimmunity.

Published
2023

3. Approach to Mycosis Fungoides in children: Consensus-based recommendations

Author

Zvulunov, Alex, Neale, Holly, Stern, Jonah, Santaguida, Pasqualina, Stein, Amy Buros, Koh, Mark, Eichenfield, Lawrence F., Guitart, Joan, Goebeler, Matthias, Scarisbrick, Julia, Willemze, Rein, Coughlin, Carrie C., George, Renu, Brazzelli, Valeria, Marschalkó, Márta, Belousova, Irena, Querfeld, Christiane, Bagot, Martine, Szepietowski, Jacek C., Papadavid, Evangelina, Quaglino, Pietro, Hoeger, Peter, Ortiz-Romero, Pablo L., Nikolaou, Vasiliki, Dummer, Reinhard, Aung, Phyu P., Lawley, Leslie, Morel, Kimberly D., Ngan, Bo, Wain, Mary, Gameiro, Ana, Lacy-Niebla, Rosa María, and Pope, Elena

Published
2024
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13. Rac2-deficiency leads to exacerbated and protracted colitis in response to Citrobacter rodentium infection.

Author

Fattouh, Ramzi, Guo, Cong-Hui, Lam, Grace Y, Gareau, Melanie G, Ngan, Bo-Yee, Glogauer, Michael, Muise, Aleixo M, and Brumell, John H

Subjects
Colon, Animals, Mice, Knockout, Mice, Citrobacter rodentium, Enterobacteriaceae Infections, Colitis, rac GTP-Binding Proteins, Male, Knockout, General Science & Technology
Abstract

Recent genetic-based studies have implicated a number of immune-related genes in the pathogenesis of inflammatory bowel disease (IBD). Our recent genetic studies showed that RAC2 is associated with human IBD; however, its role in disease pathogenesis is unclear. Given Rac2's importance in various fundamental immune cell processes, we investigated whether a defect in Rac2 may impair host immune responses in the intestine and promote disease in the context of an infection-based (Citrobacter rodentium) model of colitis. In response to infection, Rac2(-/-) mice showed i) worsened clinical symptoms (days 13-18), ii) increased crypt hyperplasia at days 11 and 22 (a time when crypt hyperplasia was largely resolved in wild-type mice; WT), and iii) marked mononuclear cell infiltration characterized by higher numbers of T (CD3(+)) cells (day 22), compared to WT-infected mice. Moreover, splenocytes harvested from infected Rac2(-/-) mice and stimulated in vitro with C. rodentium lysate produced considerably higher levels of interferon-γ and interleukin-17A. The augmented responses observed in Rac2(-/-) mice did not appear to stem from Rac2's role in NADPH oxidase-driven reactive oxygen species production as no differences in crypt hyperplasia, nor inflammation, were observed in infected NOX2(-/-) mice compared to WT. Collectively, our findings demonstrate that Rac2(-/-) mice develop more severe disease when subjected to a C. rodentium-induced model of infectious colitis, and suggest that impaired Rac2 function may promote the development of IBD in humans.

Published
2013

19. Impaired Wnt/β-catenin pathway leads to dysfunction of intestinal regeneration during necrotizing enterocolitis

Author

Li, Bo, Lee, Carol, Cadete, Marissa, Zhu, Haitao, Koike, Yuhki, Hock, Alison, Wu, Richard Y., Botts, Steven R., Minich, Adam, Alganabi, Mashriq, Chi, Lijun, Zani-Ruttenstock, Elke, Miyake, Hiromu, Chen, Yong, Mutanen, Annika, Ngan, Bo, Johnson-Henry, Kathene C., De Coppi, Paolo, Eaton, Simon, Määttänen, Pekka, Delgado-Olguin, Paul, Sherman, Philip M., Zani, Augusto, and Pierro, Agostino

Published
2019
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20. NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity

Author

Sharfe, Nigel, primary, Dalal, Ilan, additional, Naghdi, Zahra, additional, Lefaudeux, Diane, additional, Vong, Linda, additional, Dadi, Harjit, additional, Navarro, Hector, additional, Tasher, Diana, additional, Ovadia, Adi, additional, Zangen, Tzili, additional, Ater, Dorit, additional, Ngan, Bo, additional, Hoffmann, Alexander, additional, and Roifman, Chaim M., additional

Published
2023
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27. Hereditary Mucin Deficiency Caused by Biallelic Loss of Function of MUC5B

Author

Costain, Gregory, Liu, Zhen, Mennella, Vito, Radicioni, Giorgia, Goczi, Adrienn N, Albulescu, Alexandra, Walker, Susan, Ngan, Bo, Manson, David, Vali, Reza, Khan, Meraj, Palaniyar, Nades, Hill, David B., Hall, David A., Marshall, Christian R., Knowles, Michael, Zariwala, Maimoona A., Kesimer, Mehmet, Dell, Sharon D., Costain, Gregory, Liu, Zhen, Mennella, Vito, Radicioni, Giorgia, Goczi, Adrienn N, Albulescu, Alexandra, Walker, Susan, Ngan, Bo, Manson, David, Vali, Reza, Khan, Meraj, Palaniyar, Nades, Hill, David B., Hall, David A., Marshall, Christian R., Knowles, Michael, Zariwala, Maimoona A., Kesimer, Mehmet, and Dell, Sharon D.

Abstract

Rationale: Mucin homeostasis is fundamental to airway health. Upregulation of airway mucus glycoprotein MUC5B is observed in diverse common lung diseases and represents a potential therapeutic target. In mice, Muc5b is required for mucociliary clearance and for controlling inflammation after microbial exposure. The consequences of its loss in humans are unclear. Objectives: The goal of this study was to identify and characterize a family with congenital absence of MUC5B protein. Methods: We performed whole-genome sequencing in an adult proband with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infection. Deep phenotyping over a 12-year period included assessments of pulmonary radioaerosol mucociliary clearance. Genotyping with reverse phenotyping was organized for eight family members. Extensive experiments, including immunofluorescence staining and mass spectrometry for mucins, were performed across accessible sample types. Measurements and Main Results: The proband, and her symptomatic sibling who also had extensive sinus disease with nasal polyps, were homozygous for a novel splicing variant in the MUC5B gene (NM_002458.2: c.1938 + 1G>A). MUC5B was absent from saliva, sputum, and nasal samples. Mucociliary clearance was impaired in the proband, and large numbers of apoptotic macrophages were present in sputum. Three siblings heterozygous for the familial MUC5B variant were asymptomatic but had a shared pattern of mild lung function impairments. Conclusions: Congenital absence of MUC5B defines a new category of genetic respiratory disease. The human phenotype is highly concordant with that of the Muc5b-/- murine model. Further study of individuals with decreased MUC5B production could provide unique mechanistic insights into airway mucus biology.

Published
2022

28. Single Nucleotide Polymorphisms That Increase Expression of the Guanosine Triphosphatase RAC1 Are Associated With Ulcerative Colitis

Author

Muise, Aleixo M., Walters, Thomas, Xu, Wei, Shen–Tu, Grace, Guo, Cong–Hui, Fattouh, Ramzi, Lam, Grace Y., Wolters, Victorien M., Bennitz, Joshua, van Limbergen, Johan, Renbaum, Paul, Kasirer, Yair, Ngan, Bo–Yee, Turner, Dan, Denson, Lee A., Sherman, Philip M., Duerr, Richard H., Cho, Judy, Lees, Charlie W., Satsangi, Jack, Wilson, David C., Paterson, Andrew D., Griffiths, Anne M., Glogauer, Michael, Silverberg, Mark S., and Brumell, John H.

Published
2011
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30. Hereditary Mucin Deficiency Caused by Biallelic Loss of Function of MUC5B

Author

Costain, Gregory, primary, Liu, Zhen, additional, Mennella, Vito, additional, Radicioni, Giorgia, additional, Goczi, Adrienn N., additional, Albulescu, Alexandra, additional, Walker, Susan, additional, Ngan, Bo, additional, Manson, David, additional, Vali, Reza, additional, Khan, Meraj, additional, Palaniyar, Nades, additional, Hill, David B., additional, Hall, David A., additional, Marshall, Christian R., additional, Knowles, Michael, additional, Zariwala, Maimoona A., additional, Kesimer, Mehmet, additional, and Dell, Sharon D., additional

Published
2022
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