Biology subjects

Kim, B. H.

Publications and source records attributed to Kim, B. H..

7 recordsLinked to original sources

bioRxiv2026

Maternal vaccination timing shapes the composition and maturation of antibody clonotypes transferred to the newborn

Newborns rely on maternally transferred antibodies for immune protection, acquired across the placenta and through breast milk. Despite this importance, how closely the inherited antibody repertoire resembles the mothers has not been examined at the clonotypic level. We combined BCR-Seq with proteomic Ig-Seq to track SARS-CoV-2-specific antibody clonotypes across maternal blood, cord blood, and breast milk from six mRNA-immunized pregnant individuals. Vaccination earlier in gestation generated more diverse peak IgG repertoires but greater contraction before delivery, yielding fewer transferred clonotypes. Vaccination later in gestation produced more restricted peak repertoires, but more clonotypes persisted to delivery and transferred to cord. Infant cord was enriched for persistent, highly somatically mutated, and intraclonally diverse IgG clonotypes, consistent with preferential transfer of affinity-matured antibodies. In contrast, breast milk IgA repertoires were largely distinct from systemic repertoires and underwent substantial remodeling despite stable antigen titers. These findings define molecular determinants of passive immunity shaped by vaccination timing relevant to optimizing maternal immunization.

immunology↗

bioRxiv2026

Molecular-level analysis of serum IgG repertoires in COVID-19-vaccinated people with cystic fibrosis identifies abundant convergent antibodies

BackgroundPeople with cystic fibrosis (pwCF) are at increased risk of severe disease following respiratory viral infections including influenza and respiratory syncytial virus, and were therefore given priority for COVID-19 vaccination. Retrospective epidemiological data have revealed a lower incidence of SARS-CoV-2 infection and a reduced fatality rate among pwCF than in the general population, possibly from the stringent infection control measures and early adoption of protective behaviors. Despite several reports of adequate binding and neutralizing titers after vaccination, the molecular features of vaccine-elicited serum antibody repertoires in pwCF remain unknown. MethodsWe performed high-resolution proteomic analysis of serum IgG, combined with next-generation sequencing of B cells, to quantitatively profile Spike (S)-reactive serological repertoires from nine infection-naive pwCF after two doses of COVID-19 mRNA vaccine. We recombinantly expressed 20 IgG clonotypes from 6 pwCF as monoclonal antibodies (mAbs) and measured their binding and neutralization against vaccine-strain and variant viruses. ResultsAll donors mounted strong binding and neutralizing titers to vaccine-strain virus. Ig-Seq revealed diverse serum repertoires in all vaccinees, with antibodies targeting the receptor-binding domain (RBD) comprising 64% of each circulating repertoire by abundance. Several serum IgG clonotypes identified across our cohort shared identical or similar IGHV and CDRH3 amino acid sequences with serum IgG from other pwCF or S-reactive mAbs isolated from non-CF individuals. These convergent antibodies made up 14.6% of the anti-S repertoires in our cohort, reaching 24.8% in one pwCF. Convergent antibodies tended to be RBD-reactive and enriched in specific IGHV; surprisingly, a higher abundance of convergent antibodies in serum correlated with a lower breadth of serum neutralization. All 20 mAbs bound Wuhan S with high affinity (EC50 < 10 nM), and only RBD-reactive mAbs conferred neutralization to vaccine or variant pseudovirus. While most mAbs bound both the B.1.617.2 (Delta, 17/20) and B.1.1.529 (Omicron, 12/20) strains, convergent mAbs were less likely to bind either variant. ConclusionsPost-vaccine serum IgG repertoires in pwCF are dominated by RBD-focused, high-affinity antibodies and include a substantial convergent component shared with non-CF vaccinees. These findings demonstrate that pwCF mount antibody responses comparable to the general population, and a large group of convergent antibodies may contribute to strain-specific rather than cross-variant immunity.

immunology↗

bioRxiv2026

Spatial tumor microenvironmental architecture of chemoradiotherapy-resistant residual esophageal squamous cell carcinoma

PurposeResidual ESCC after neoadjuvant CCRT reflects incomplete treatment response and carries a high risk of recurrence. We sought to define the spatial tumor microenvironmental features of CCRT-resistant residual ESCC -- using tumor regression grade (TRG) 2-3 tumors as a model of poor pathologic response -- with mechanistic refinement at single-cell resolution and outcome assessment in internal and external cohorts. Experimental DesignWe profiled post-CCRT ESCC tissue microarray (TMA) cores by Visium FFPE whole-transcriptome spatial transcriptomics and orthogonal Xenium single-cell-resolution in situ profiling on serial sections from the same TMA blocks. Spot-level cell-type composition was inferred by CellDART deconvolution against a published ESCC single-cell RNA sequencing (scRNAseq). Local malignant-cell-enriched regions were defined by CancerFinder. We additionally re-analyzed the scRNAseq dataset to characterize SPP1 and CXCL5 macrophage states and their ligand-receptor signaling using CellChat. Outcome associations were evaluated in the SNUH cohort and externally tested in the TCGA ESCC cohort. ResultsTRG 2-3 residual tumors exhibited effector immune-cell exclusion from malignant-cell-enriched regions, SPP1/CXCL5 macrophage accumulation, microvascular rarefaction, and proliferative-metabolic reprogramming. Single-cell re-analysis confirmed that CXCL5 macrophages constitute a transcriptional subset of the broader SPP1 macrophage population. CellChat showed that SPP1 macrophages dominantly signal through SPP1-CD44 and SPP1-integrin axes to stromal and epithelial targets, and additionally engage immunosuppressive NECTIN2-TIGIT, CD86-CTLA4, and LGALS9-HAVCR2 programs with CD8 T cells, providing a mechanistic context for local immune exclusion. Visium LIANA and Xenium distance-gradient profiling localized SPP1-associated signaling preferentially to tumor cells and CAFs. Higher SPP1 expression and lower endothelial abundance were associated with shorter disease-free survival in the SNUH cohort. Higher SPP1 expression was also associated with shorter disease-free survival in the independent TCGA ESCC cohort. ConclusionsCCRT-resistant residual ESCC is characterized by a spatially organized tumor microenvironmental niche centered on SPP1-associated macrophage programs and microvascular rarefaction. These spatially resolved findings identify candidate macrophage- and vasculature-targeted axes for overcoming treatment resistance. Translational RelevancePatients with esophageal squamous cell carcinoma (ESCC) who harbor residual disease after neoadjuvant chemoradiotherapy (CCRT) remain at high risk of recurrence, yet the spatial biology of this resistant residual state has been poorly defined. Here, we combine Visium whole-transcriptome and Xenium single-cell-resolution spatial transcriptomics with single-cell RNA-seq re-analysis and external TCGA context to define the tumor microenvironmental architecture of CCRT-resistant residual ESCC. The resistant niche is characterized by effector immune-cell exclusion from malignant-cell-enriched regions, accumulation of SPP1/CXCL5 macrophage programs that signal to tumor cells and cancer-associated fibroblasts through SPP1-CD44 and SPP1-integrin axes, microvascular rarefaction, and proliferative-metabolic reprogramming. These findings define a coordinated spatial tumor microenvironmental signature of CCRT-resistant residual ESCC and nominate macrophage-tumor/stromal interactions and vascular injury as biologic axes that may help guide future strategies to overcome treatment resistance.

cancer biology↗

bioRxiv2026

Cholesterol differentially regulates α-synuclein binding across membrane packing regimes

-Synuclein (Syn) is an intrinsically disordered protein that preferentially binds anionic membranes with lipid packing defects. Cholesterol is an abundant membrane component that regulates packing and organization within membranes, yet its effect on Syn binding remains unclear as prior studies report both cholesterol-mediated enhancement and suppression. Here, we investigated whether these conflicting effects reflect differences in the intrinsic packing state of the phospholipid bilayer. Using a quantitative fluorescence microscopy-based binding assay, we measured Syn binding preferences among reconstituted phosphatidylcholine/phosphatidylserine membranes with varied cholesterol content, lipid tail chemistry, and vesicle curvature. We found that cholesterols effect depended on the underlying packing regime of the membrane. In defect-rich membranes, cholesterol reduced Syn binding, consistent with cholesterol tightening lipid packing and reducing Syn-accessible defects. In membranes with intermediate defect content, cholesterol enhanced binding, whereas tightly packed membranes remained largely insensitive to cholesterol except when high cholesterol content was combined with high membrane curvature. Curvature further shaped these responses, with high curvature compressing cholesterol-dependent differences between membrane compositions. These results show that cholesterol does not universally promote or inhibit Syn binding. Instead, cholesterol regulates Syn-membrane interactions through a packing-regime-dependent mechanism shaped by both lipid tail chemistry and membrane curvature. This framework helps reconcile opposing reports in the literature and highlights membrane physical state as a key determinant of how cholesterol modulates Syn binding. SignificanceSyn is a membrane-binding protein associated with Parkinsons disease, but the role of cholesterol in regulating its membrane interactions has remained unclear. Some studies report that cholesterol enhances Syn association with membranes, whereas others show that cholesterol suppresses it. This work helps explain why both outcomes can occur. We show that cholesterols effect depends on the membranes underlying packing state: cholesterol can reduce, enhance, or have little effect on Syn binding depending on the membrane environment. These findings shift the question from whether cholesterol is generally pro- or anti-binding to how cholesterol reshapes the membrane physical states that control Syn association.

biophysics↗

bioRxiv2026

Membrane Phase, Charge, and Curvature Regulate α-Synuclein Binding Dynamics

-Synuclein (Syn) is an intrinsically disordered protein whose interactions with lipid membranes are central to both its physiological function and its role in synucleopathies. While membrane charge, phase, and curvature are each known to influence Syn binding, these properties are typically examined independently, leaving their combined effects on both equilibrium and dynamic membrane association unresolved. Here, we systematically investigate how membrane phase and charge jointly regulate Syn binding, curvature sensitivity, and exchange dynamics using fluorescence microscopy, circular dichroism spectroscopy, and fluorescence recovery after photobleaching (FRAP), complemented by coarse-grained molecular dynamics simulations. Under zwitterionic conditions, Syn preferentially binds highly curved gel-phase membranes, driven by curvature-dependent enrichment of packing defects arising from faceted vesicle morphologies. Incorporation of anionic lipids selectively enhances binding in liquid-phase membranes while attenuating curvature-dependent partitioning in gel-phase membranes. Dynamic measurements reveal that membrane phase and charge also govern the stability of membrane-associated Syn, with gel-phase membranes and anionic lipids promoting kinetically stabilized states. Simulations show that curvature-induced defect formation is strongly amplified in gel-phase membranes but largely insensitive to charge. These findings establish that Syn-membrane interactions are governed by a cooperative interplay between membrane phase, curvature, and charge and highlight the importance of resolving both thermodynamic and kinetic contributions to protein-membrane binding.

biophysics↗

bioRxiv2026

From Garden Soil to Bio-electricity: Utilizing Rhizosphere Diversity for Microbial Fuel Cell Operation

This study investigates the potential of the garden rhizosphere as a source of electrochemically active bacteria (EAB) for operating microbial fuel cells (MFCs). We evaluated a diverse array of garden flora, including vegetables (lettuce, Chinese cabbage), flowering plants (August lily, peppermint), and woody species (pine, oak, ginkgo, and bush clover). Among the tested groups, MFCs inoculated with peppermint and ginkgo rhizosphere microbiotas exhibited the highest current densities within their respective categories, significantly outperforming control groups without plant components. 16S rRNA gene microbial community analysis revealed that the initial rhizosphere environment acts as a decisive selective pressure, shaping distinct anode biofilms based on plant types (herbaceous vs. woody). Despite these structural differences in microbial assembly, high current generation was achieved in both peppermint and ginkgo systems, suggesting a high degree of functional redundancy within the rhizosphere-derived consortia. These findings demonstrate that various garden ecosystems can serve as robust biological reservoirs for MFC operation, where diverse microbial configurations are capable of sustaining efficient bio-electrochemical energy conversion.

microbiology↗

bioRxiv2020

Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF){beta}1 is highly elevated following HI and that delivering an antagonist for TGF{beta} receptor activin-like kinase 5 (ALK5) - SB505124 - 3 days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated LC3 (light chain 3), a key protein known to mediate autophagy. However, those studies did not determine whether 1) SB was acting directly on the CNS and 2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist 3 days after HI reduced actively apoptotic cells by [~]90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting 3 days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

neuroscience↗