Biology subjects

Hur, K.

Publications and source records attributed to Hur, K..

5 recordsLinked to original sources

bioRxiv2025

VO: The Vaccine Ontology

With the widespread use of vaccines in research and clinical settings, there is an urgent need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO models ontologically vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as RxNorm, CVX, FDA, and USDA. Various VO use cases exist. VO facilitates vaccine standardization in resources such as the VIOLIN vaccine database, ImmPort, and the Vaccine Adjuvant Compendium (VAC). Semantic queries can be made to query VO. VO has been shown to enhance experimental and clinical vaccine data analysis and vaccine literature mining. Overall, VO standardizes vaccine modeling and representation and greatly supports vaccine AI research in the Semantic Web era.

bioinformatics↗

bioRxiv2024

Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPK

Phospholipase C beta (PLC{beta}) exerts diverse biological processes, including inflammatory responses and neurogenesis; however, its role in bone cell function is largely unknown. Among the PLC{beta} isoforms ({beta}1-{beta}4), we found that PLC{beta}4 was most highly upregulated during osteoclastogenesis. In this study, we used global knockout and osteoclast lineage-specific PLC{beta}4 conditional knockout (LysM-PLC{beta}4-/-) mice and demonstrated that PLC{beta}4 is a crucial regulator of receptor activator of nuclear factor {kappa}B ligand (RANKL)-induced osteoclast differentiation. Deletion of PLC{beta}4, both globally and in the osteoclast lineage, resulted in a significant reduction in osteoclast formation and the downregulation of osteoclast marker genes. Importantly, LysM-PLC{beta}4-/- male mice exhibited greater bone mass and a lower number of osteoclasts in vivo than their wild-type littermates, without altering osteoblast function. Mechanistically, we found that PLC{beta}4 forms a complex with p38 mitogen-activated protein kinase (MAPK) and MAPK kinase 3 (MKK3) in response to RANKL, thereby modulating p38 activation. An immunofluorescence assay further confirmed the colocalization of PLC{beta}4 with p38 after RANKL exposure. Moreover, p38 activation rescued the impaired osteoclast formation and restored the reduced p38 phosphorylation due to PLC{beta}4 deficiency. Thus, our findings reveal that PLC{beta}4 controls osteoclastogenesis via the RANKL-dependent MKK3-p38 MAPK pathway, and PLC{beta}4 may be a potential therapeutic candidate for bone diseases such as osteoporosis.

cell biology↗

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↗

bioRxiv2019

Design of DNA Origami Diamond Photonic Crystals

Self-assembled photonic crystals have proven to be a fascinating class of photonic materials for non-absorbing structural colorizations over large areas and in diverse relevant applications, including tools for on-chip spectrometers and biosensors, platforms for reflective displays, and templates for energy devices. The most prevalent building blocks for the self-assembly of photonic crystals are spherical colloids and block copolymers (BCPs) due to the generic appeal of these materials, which can be crafted into large-area 3D lattices. However, due to the intrinsic limitations of these structures, these two building blocks are difficult to assemble into a direct rod-connected diamond lattice, which is considered to be a champion photonic crystal. Here, we present a DNA origami-route for a direct rod-connected diamond photonic crystal exhibiting a complete photonic bandgap (PBG) in the visible regime. Using a combination of electromagnetic, phononic, and mechanical numerical analyses, we identify (i) the structural constraints of the 50 megadalton-scale giant DNA origami building blocks that could self-assemble into a direct rod-connected diamond lattice with high accuracy, and (ii) the elastic moduli that are essentials for maintaining lattice integrity in a buffer solution. A solution molding process could enable the transformation of the as-assembled DNA origami lattice into a porous silicon- or germanium-coated composite crystal with enhanced refractive index contrast, in that a champion relative bandwidth for the photonic bandgap (i.e., 0.29) could become possible even for a relatively low volume fraction (i.e., 16 vol%).

synthetic biology↗

bioRxiv2019

Neutrophil-derived extracellular vesicles: proinflammatory trails and anti-inflammatory microvesicles

Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we investigated the similarities and differences between neutrophil-derived EV subtypes. Neutrophil-derived EVs shared similar characteristics regarding stimulators, generation mechanisms, and surface marker expression. Both neutrophil-derived EV subtypes exhibited similar functions, such as direct bactericidal activity and induction of monocyte chemotaxis via MCP-1. However, NDTR generation was dependent on the integrin signaling, while NDMV generation was dependent on the PI3K pathway. The CD16 expression level differentiated the neutrophil-derived EV subtypes. Interestingly, both subtypes showed different patterns of miRNA expression and were easily phagocytosed by monocytes. NDTRs induced M1 macrophage polarization, whereas NDMVs induced M2 macrophage polarization. Moreover, NDTRs but not NDMVs exerted protective effects against sepsis-induced lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. These results suggest a new insight into neutrophil-derived EV subtypes: proinflammatory NDTRs and anti-inflammatory NDMVs.\n\nKey pointsO_LINeutrophil-derived trails are proinflammatory extracellular vesicles that induce M1 macrophage polarization and protect against inflammation\nC_LIO_LINeutrophil-derived microvesicles are anti-inflammatory extracellular vesicles that induce M2 macrophage polarization\nC_LI

immunology↗