Biology subjects

Cho, J.-Y.

Publications and source records attributed to Cho, J.-Y..

7 recordsLinked to original sources

bioRxiv2026

Fructose utilization by GM-CSF-differentiated macrophages aggravates autoimmune inflammation via MG-derived AGE-RAGE signaling

Excessive fructose intake is increasingly associated with metabolic and inflammatory pathologies; however, the direct impact of fructose metabolism on immune cell function remains insufficiently understood. Here, we demonstrate that GM-CSF-differentiated macrophages markedly upregulate the fructose-specific transporter GLUT5, enabling efficient fructose utilization through two complementary metabolic pathways. Using 13C-fructose tracing, we identified distinct carbon fluxes via a hexokinase (HK)-dependent glycolytic route and a ketohexokinase (KHK)-ALDOB-mediated fructolytic route. The HK-dependent pathway sustains glycolytic activity under glucose-limiting conditions, stabilizing HIF-1 and preserving pro-inflammatory gene expression. Conversely, the KHK-ALDOB axis increases dihydroxyacetone phosphate (DHAP) production, leading to methylglyoxal-derived advanced glycation end-products (MG-AGEs) that engage receptor for AGE (RAGE) signaling. This activation enhances MMP9 expression in macrophages and drives Th17 differentiation in CD4 T cells, amplifying inflammatory and tissue-remodeling processes. In vivo, fructose intake exacerbates autoimmune arthritis in SKG mice, and elevated fructose-driven glycolysis and MG-AGE accumulation are observed in monocytes from patients with rheumatoid arthritis. These results link fructose-driven carbonyl stress to macrophage effector programs and downstream T cell polarization. Collectively, these findings uncover a dual fructose metabolic program that integrates nutrient stress with persistent inflammation via the MG-AGE-RAGE axis and underscore the immunometabolic risks of excessive fructose exposure.

immunology↗

bioRxiv2024

Gencube: Efficient retrieval, download, and unification of genomic data from leading biodiversity databases

MotivationWith the daily submission of numerous new genome assemblies, associated annotations, and experimental sequencing data to genome archives for various species, the volume of genomic data is growing at an unprecedented rate. Major genomic databases are establishing new hierarchical structures to manage this data influx. However, there is a significant need for tools that can efficiently access, download, and integrate genomic data from these diverse repositories, making it challenging for researchers to keep pace. ResultsWe have developed Gencube, a command-line tool with two primary functions. First, it facilitates the utility of genome assemblies, related annotations, gene set sequences, and cross-species data from various leading biodiversity databases. Second, it helps researchers intuitively explore experimental sequencing data that meets their needs and consolidates the metadata of the retrieved outputs. Availability and implementationGencube is a free and open-source tool, with its code available on GitHub: https://github.com/snu-cdrc/gencube.

bioinformatics↗

bioRxiv2023

Extracellular vesicle-mediated Transfer of miR-1 from Primary tumor Repress Metastasis Growth

Metastases originate from primary tumors that conquer distant organs. Growing evidence suggests that metastases are still under primary tumor dominance, even out of the primary territory. However, the mechanism by which primary tumors prime the fate of metastasis is unclear. Here, we investigated the influence of primary tumor-derived extracellular vesicles (pTDEs) on distant metastasis. Metastatic growth was remarkably suppressed when cells were treated with pTDEs in vitro and intravenously in a spontaneous metastatic mouse model. pTDEs from primary tumors with cancer stem cell (CSC) characteristics inhibit metastatic growth by inducing intracellular ROS/DNA double-stranded damage, thus inhibiting G2/M phase accumulation. We found that miR-1 was the most abundant in pTDEs and showed a stronger inhibitory effect when miR-1 was overloaded in pTDEs. Collectively, we demonstrated that the primary tumor could control distant metastatic cancer via primary tumor-derived EV-miR-1. Additionally, our approach suggests the development of anticancer drugs for metastasis based on pTDE-miR-1.

cancer biology↗

bioRxiv2022

Integrative mapping of the dog epigenome: reference annotation for comparative inter-tissue and cross-species studies

The domestic dog has become a valuable model in exploring multifaceted diseases and biology important for human health. Large-scale dog genome projects produced high-quality draft references but still lack comprehensive annotation of encoded functional elements. Through the integrative next generation sequencing of transcriptomes paired with histone marks and DNA methylome profiling of 11 adult tissue types, implemented in a cross-species approach, we generated a reference epigenome of a domesticated dog. Using genome orthologues and synthenies, we deciphered the dogs epigenetic code by defining distinct chromatin states, allowing for genome-wide, integratable data production. We then characterized somatic super-enhancer landscapes and showed that genes mapped on these regions are associated with a broad range of biological and disease traits and are traceable to their tissue-of-origin. Ultimately, we delineated conserved epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog for comparative biology and medical research.

genomics↗

bioRxiv2021

Widespread multi-targeted therapy resistance via drug-induced secretome fucosylation

Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post-translational cancer hallmark and the consequences thereof remain elusive. Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In both cancer cell cultures and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycoproteomes revealed that fucosylation of the antioxidant PON1 is a critical component of the therapy-induced secretome. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Non-specific and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.

cancer biology↗

bioRxiv2021

Unbuttoning the impact of N501Y mutant RBD on viral entry mechanism: A computational insight

The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a serious global threat. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for this pandemic has imposed a severe burden on the medical settings. The spike (S) protein of SARS-CoV-2 is an important structural protein playing a key role in the viral entry. This protein is responsible for the receptor recognition and cell membrane fusion process. The recent reports of the appearance and spread of new SARS-CoV-2 strain has raised alarms. It was reported that this new variant containing the prominent active site mutation in the RBD (N501Y) was rapidly spreading within the population. The reported N501Y mutation within the spikes essential part, known as the receptor-binding domain has raised several questions. Here in this study we have tried to explore the effect of N501Y mutation within the spike protein using several in silico approaches

bioinformatics↗

bioRxiv2020

Non-canonical immune response to the inhibition of DNA methylation via stabilization of endogenous retrovirus dsRNAs

5-Aza-2'-deoxycytidine, also known as decitabine, is a DNA-methyltransferase inhibitor (DNMTi) used to treat acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERV), which can induce an immune response by acting as cellular double-stranded RNAs (dsRNAs). Here, we employ an image-based screening platform to identify dsRNA-binding factors that mediate the downstream effect of ERV induction. We find that Staufen1 (Stau1) knockdown decreases the interferon signature and rescues decitabine-mediated cell death. Moreover, Stau1 directly binds to ERV RNAs and stabilizes them, together with a long non-coding RNA TINCR. We further show that TINCR enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that AML patients with low Stau1 and TINCR expressions exhibits inferior treatment outcomes to the DNMTi therapy. Our study reveals that decitabine-mediated cell death is a consequence of complex interactions among different dsRNA-binding proteins for access to their common dsRNA targets. HIGHLIHGTSO_LIImage-based RNAi screening reveals multiple dsRBPs regulate response to decitabine C_LIO_LIStau1 binds to ERV RNAs and affects their stability and subcellular localization C_LIO_LITINCR binds to Stau1 and enhances Stau1-ERV interactions C_LIO_LIAML/MDS patients with low Stau1 and TINCR expressions show poor response to DNMTis C_LI

molecular biology↗