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dc.contributor.authorLoh, Jia Tongen_US
dc.contributor.authorTeo, Joey Kay Huien_US
dc.contributor.authorKannan, Srinivasaraghavanen_US
dc.contributor.authorVerma, Chandra Shekharen_US
dc.contributor.authorLim, Hong-Hwaen_US
dc.contributor.authorLam, Kong-Pengen_US
dc.identifier.citationLoh, J. T., Teo, J. K. H., Kannan, S., Verma, C. S., Lim, H. & Lam, K. (2023). Disrupting the Dok3–Card9 interaction with synthetic peptides enhances antifungal effector functions of human neutrophils. Pharmaceutics, 15(7), 1780-.
dc.description.abstractInvasive fungal disease is an emerging and serious public health threat globally. The expanding population of susceptible individuals, together with the rapid emergence of multidrug-resistant fungi pathogens, call for the development of novel therapeutic strategies beyond the limited repertoire of licensed antifungal drugs. Card9 is a critical signaling molecule involved in antifungal defense; we have previously identified Dok3 to be a key negative regulator of Card9 activity in neutrophils. In this study, we identified two synthetic peptides derived from the coiled-coil domain of Card9, which can specifically block Dok3-Card9 binding. We showed that these peptides are cell-permeable, non-toxic, and can enhance antifungal cytokine production and the phagocytosis of human neutrophils upon fungal infection. Collectively, these data provide a proof of concept that disrupting the Dok3-Card9 interaction can boost the antifungal effector functions of neutrophils; they further suggest the potential utility of these peptide inhibitors as an immune-based therapeutic to fight fungal infection.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipMinistry of Health (MOH)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.rights© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleDisrupting the Dok3–Card9 interaction with synthetic peptides enhances antifungal effector functions of human neutrophilsen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationBioinformatics Institute, A*STARen_US
dc.contributor.organizationDepartment of Biological Sciences, NUSen_US
dc.contributor.organizationSingapore Immunology Network, A*STARen_US
dc.contributor.organizationYong Loo Lin School of Medicine, NUSen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsAntifungal Immunityen_US
dc.description.acknowledgementThis work is supported by the Singapore Ministry of Health’s National Medical Research Council under its Open-Fund-Individual Research Grant (NMRC/OFIRG19may-0083) to KPL, HHL, and JTL, Open Fund-Young Individual Research Grant (NMRC/OFYIRG21nov-0035) to JTL and A*STAR core grant to KPL.en_US
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