Biology subjects

Kang, M. S.

Publications and source records attributed to Kang, M. S..

5 recordsLinked to original sources

bioRxiv2026

μMap-uAA: Photocatalytic proximity labeling targeted with single-residue precision

Mapping protein microenvironments with residue-level precision in living cells remains challenging. We report Map-uAA, a genetically encoded proximity labeling platform that uses unnatural amino acid incorporation to install a tetrazine-quenched iridium photocatalyst at user-defined protein sites through click chemistry. Photocatalysis is activated by covalent attachment to the incorporated uAA, enabling localized catalytic labeling of proximal biomolecules. Applied to membrane receptors, Map-uAA captures domain- and time-dependent GPCR interaction networks with residue-level spatial precision.

biochemistry↗

bioRxiv2025

Novel transcription factor BTNL9 enhances tumor suppression and drug sensitivity in non-small cell lung cancer through cell cycle regulation

BackgroundButyrophilins (BTNs) are immunoglobulin superfamily proteins involved in immune regulation. Among them, BTNL9 has unique structural features, including a bZIP-like domain, suggesting a potential transcriptional role. While BTNL9 is known to suppress T cell activation, its function in cancer remains largely unexplored. Recent studies suggest it may inhibit tumor progression and correlate with improved prognosis in multiple cancers. However, its molecular mechanisms and regulatory impact on lung cancer remain unclear. This study investigates the role of BTNL9 as a transcription factor and its implications for tumor progression and therapy. MethodsChIP-seq identified BTNL9-binding sites, followed by RNA-seq to assess transcriptomic profiles and validated by western blot. Drug sensitivity was evaluated through cytotoxicity assays. A xenograft model was applied to assess the effect of BTNL9 on tumor growth. TCGA data analysis examined correlations with survival, cell cycle regulators, and immune infiltration. ResultsChIP-seq identified 26,610 BTNL9 binding peaks, mapping to 9,707 genes near transcription start sites. RNA-seq and western blotting showed BTNL9 regulates cell cycle (E2F1, CDKN1A, CDK1, CDC25C, FOXM1), DNA replication (MCM2/3/7, ORC6), and p53-related transcription (BBC3, GADD45A). Integrative analysis found that 74.8% of differentially expressed genes were directly regulated by BTNL9. Functionally, BTNL9 overexpression induced cell cycle arrest, reduced proliferation, and suppressed tumor growth in vivo. BTNL9 enhanced bortezomib sensitivity in both A549 and NCI-H460 cells, with etoposide effects being more pronounced in A549. Higher BTNL9 levels strongly suppressed the expression of FOXM1, CDC25C, CDK1, CDK2, CCNA2 and CCNB1 and negatively correlated with these markers in LUAD TCGA data. Elevated BTNL9 expression was associated with improved survival, complete remission, and increased immune infiltration, including macrophages, CD8+ T cells, NK cells, and B cells in cancer tissues. ConclusionsBTNL9 functions as a transcription factor, suppresses tumor growth, and enhances drug sensitivity. Its correlation with survival and immune infiltration suggests potential role as a tumor suppressor and predictive biomarker for chemotherapy response.

cancer biology↗

bioRxiv2024

Anatomical Region-Specific Transcriptomic Signatures and the Role of Epithelial Cells in Pterygium Inflammation: A Multi-Omics Analysis

BackgroundThe anatomy of pterygium consists of the head, neck, and body. Prior studies have examined the three parts collectively, yet the treatment methods and their success rates differ based on the anatomical characteristics. In this study, we divide the pterygium tissue into Main (head and neck) and Acc (body) to investigate its pathogenesis across regions. PurposesThis study aims to understand the pathogenesis and identify potential therapeutic targets of pterygium. Through a robust multi-omics analysis of bulk and single-cell RNA sequencing (RNA-seq) data from pterygium patients, we focus on the expression of inflammatory and mitochondrial energy pathways and identify potential genes responsible for the upregulated pathways in pterygium. MethodsWe collected bulk RNA-seq data from six pterygium patients and single-cell RNA-seq data from two pterygium patients. We then investigated the pathway enrichment, pathway correlation, differential gene expressions, protein-protein interactions, and cell-cell communications of pterygium. ResultsFrom the analysis of bulk RNA-seq data, the distribution of sample points from the principal component analysis plot and the pathways enriched from the Gene Ontology analysis showed distinct expression patterns in the Acc group compared to the Main and control groups. This suggested the need to separate the Main and Acc regions within pterygium samples and utilize single-cell RNA-seq data to understand the differences between the Main and control groups that the bulk data could not capture. The annotation of integrated single-cell data revealed a cluster of epithelial cells containing only pterygium samples. Cells from this cluster exhibited significant contributions to the ANGPTL, IL1, and KLK signaling networks in the cell-cell communication analysis. We also observed significant upregulation of the cells in the inflammatory pathways related to integrated stress response and the renin-angiotensin-aldosterone system, both of which showed high correlations with energy metabolism pathways. Significant changes in the expression of multiple pro-inflammatory, antioxidant, and immune-related genes were also identified. ConclusionThe different expression patterns between the Main and Acc groups suggest the need to consider different anatomical regions separately in future studies of pterygium. Additionally, the significant role epithelial cells from the Main group play in the inflammation of pterygium presents a potential clinical approach to the disease.

bioinformatics↗

bioRxiv2021

Lower Aβ-PET signal in white matter lesions relates to higher extracellular free water in mixed small vessel disease and Alzheimer's pathology

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (A{beta}-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered A{beta}-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to A{beta}-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in A{beta}-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in A{beta}-PET related more closely to higher cortical A{beta} (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and A{beta}-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

neuroscience↗

bioRxiv2020

Decision value signals in the ventromedial prefrontal cortex and anhedonia across mood and psychotic disorders

Deficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for a shared transdiagnostic mechanism underlying impairments in motivation and pleasure across major depression, bipolar disorder, and schizophrenia. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during decision-making were dampened in individuals with greater motivational and hedonic deficits, regardless of the primary diagnosis. This relationship remained significant while controlling for diagnosis-specific symptoms of mood and psychosis, such as depression as well as positive and negative symptoms. Our results demonstrate that dysfunction in the vmPFC during value-based decision-making is specifically linked to motivational and hedonic impairments across various psychiatric conditions. These findings provide a quantitative neural target for the potential development of novel treatments for amotivation and anhedonia.

neuroscience↗