Biology subjects

Kwon, S. S.

Publications and source records attributed to Kwon, S. S..

4 recordsLinked to original sources

bioRxiv2026

Generation of Human Taste Bud Organoids as a Human-Mimetic Platform for Modeling Taste Perception

We established a human taste bud organoid system derived from circumvallate papillae. This model has been highly anticipated in the field of taste research, where feasible approaches for validating taste biology discovered in rodent models have been limited. Through a stepwise exploratory strategy, we systematically identified and optimized the niche factors required to maintain taste bud organoids and promote their differentiation. This human taste bud organoid system comprises Type I-IV taste receptor cells (TRCs) as well as stem/progenitor cells, and its sensory receptor cells exhibit calcium responses to taste stimuli. Using this system, we identified robust Wnt signaling as a requirement for optimal TRC fate progression, uncovered a human-specific transcriptional program in LGR5 cells, and identified previously unrecognized molecular markers for Type I TRCs. By recapitulating native human taste bud cell diversity and function, this organoid provides a tractable platform for studying human taste biology and dysfunction.

developmental biology↗

bioRxiv2026

A macrophage-derived noncanonical WNT niche drives immune exclusion in pancreatic cancer

Background and AimsPancreatic ductal adenocarcinoma (PDAC) is characterized by profound immune exclusion and resistance to immunotherapy. Although WNT signaling has been implicated in PDAC, its cellular source within the tumor microenvironment and its contribution to immune suppression remain poorly defined. This study investigated whether myeloid-derived WNT signaling promotes PDAC progression. MethodsTranscriptomic data from human PDAC cohorts, including The Cancer Genome Atlas (TCGA), and published single-cell RNA sequencing datasets were analyzed. Macrophage-associated WNT5A expression in human PDAC biopsies was assessed using in situ hybridization and immunofluorescence. Macrophage-derived WNT secretion was genetically disrupted using macrophage-specific Porcn knockout mice in orthotopic and subcutaneous KPC tumor models. Lineage-resolved spatial organization of macrophage subsets was characterized using Ms4a3 fate-mapping double-reporter mice with immunofluorescence and imaging mass cytometry. Macrophages-CD8 T cells interactions were assessed using tumor-educated macrophage conditioned media, pharmacologic ARG1 inhibition, and in vivo CD8 T cell depletion. ResultsPDAC tumors with high macrophage signatures showed enrichment of noncanonical WNT signaling, and macrophage-associated WNT5A was detected in human biopsies. Disruption of macrophage-derived WNT secretion suppressed tumor growth, reversed immune exclusion, and enhanced cytotoxic CD8 T cell infiltration. Spatial lineage-resolved analysis demonstrated progressive accumulation of Hexb tissue-resident macrophages that dominated advanced lesions and formed a WNT-rich niche closely associated with Trem2Arg1 monocyte-derived macrophages. Mechanistically, macrophage-derived noncanonical WNT activated a JNK/c-Jun-ARG1 axis that inhibited CD8 T cell proliferation, an effect abolished by myeloid WNT loss. ConclusionsMyeloid-derived noncanonical WNT establishes a lineage-structured macrophage niche that enforces immune exclusion in PDAC. Targeting macrophage-restricted WNT signaling represents a promising strategy to reprogram the PDAC immune microenvironment.

cancer biology↗

bioRxiv2023

Serum albumin maintains Wnt water-solubility and activity

Wnt proteins regulate adult tissue homeostasis and repair by driving stem cell self-renewal and differentiation. High-performance Wnt preparations have enormous therapeutic potential, especially alongside various stem cell technologies. Currently, most of these Wnt preparations contain FBS or the detergent CHAPS to maintain Wnt solubility and activity. Recently, afamin was identified as a serum factor that solubilizes Wnt3a in conditioned media (CM), obviating the requirement for animal sera. Here, we report serum albumin (SA) is required for afamin-mediated solubilization of Wnt3a in CM. Moreover, SA-mediated solubilization of purified Wnt3a in tubes does not require afamin. This means conventional CHAPS-Wnt3a preparations can be modified into SA-purified Wnt3a (SA-pWnt3a) preparations by exchanging CHAPS for SA through dialysis. SA-pWnt3a preparations effectively promote the growth of human stem cell organoids. These data suggest SA as a physiological factor for maintaining Wnt3a activity in therapeutic applications.

biochemistry↗

bioRxiv2019

Effect of Antimicrobial Stewardship with Rapid MALDI-TOF Identification and Vitek 2 Antimicrobial Susceptibility Testing on Hospitalization Outcome

IntroductionRapid organism identification (ID) and antimicrobial susceptibility testing (AST) along with antibiotic stewardship (ASP) are critical to appropriate treatment. We sought to capture time for bacterial culture and initiation of appropriate therapy for patients, from 2017 (without MALDI-TOF/Vitek 2 and ASP) and 2018 (with MALDI-TOF/Vitek 2 and ASP).\n\nMethodsEligible patients admitted to our hospital with a positive sputum, blood, or urine culture. Sequential patients were retrospectively obtained from March 1 to May 31, 2017. Seventy-seven patients from 2017 were compared to 77 patients from 2018. A time-in-motion study was performed to compare time to identification (ID), AST results, and ASP team intervention for the two periods. Data were entered into SPSS (ver 25) for analysis. Results are reported as mean ({+/-} SD) or percentage.\n\nResultsTime to organism ID was significantly faster in 2018 (2018 24.9 {+/-} 14.4, 2017 33.8 {+/-} 17 h, p=0.001). Time to AST results was also significantly faster for patients in 2018 compared to 2017 (18.2 {+/-} 14 compared to 28.5 {+/-} 14.9 h, p<0.001). ASP team recommended significantly more adjustments to empiric antimicrobial therapy in 2018 (28% of 2018 vs. 2% in 2017, p< 0.001). Length of hospital stay was significantly shorter in 2018 compared to 2017 (2018 10.7 {+/-} 11.1 days and 2017 15.5 {+/-} 18.1 days, p=0.05).\n\nConclusionsUse of MALDI-TOF/Vitek 2 leads to an average 21.5 h faster ID and AST results that can be acted upon by ASP for appropriate antimicrobial recommendations.

microbiology↗