Biology subjects

Kang, J. W.

Publications and source records attributed to Kang, J. W..

5 recordsLinked to original sources

bioRxiv2025

RamanOmics Decodes Spatial Vibrational-Molecular Architecture and Rewiring in Aging and Repair

Aging and tissue repair involve multilayered and spatially heterogeneous remodeling across transcriptional, biochemical, and cellular dimensions, yet prevailing definitions rely on isolated molecular markers that obscure how biochemical and transcriptional states co-evolve in tissues. Here we present RamanOmics, a multimodal framework that integrates single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics, and label-free Raman imaging to map the spatial vibrational-biochemical and molecular architecture of aging and senescence directly in intact tissues. Applied to mouse lung and skin, RamanOmics generates spatially resolved biochemical-molecular maps revealing tissue-specific programs: lung senescent cells are enriched for extracellular matrix (ECM) remodeling and TGF-{beta} signaling (Serpine1, Dab2, Igfbp7), whereas skin senescence is dominated by keratinization and barrier homeostasis modules (Krt10, Lor, Sbsn). Across tissues, we identify a conserved branched-chain fatty-acid-linked biochemical profile and Raman signature (1131-1135 cm-{superscript 1}) that robustly marks p21 senescent cells. To unify these layers, we develop a machine learning derived "multimodal barcode" that quantitatively integrates biochemical and transcriptional features, enabling non-destructive identification of senescence in situ. In a wound-healing model, RamanOmics further reveals coordinated reactivation of barrier-repair programs in senescent cells, marked by upregulation of Krt10, Lor, Sbsn, Sfn, and Dmkn together with matching increases in lipid-associated Raman signatures, confirming biological generalizability beyond steady-state aging. By directly integrating gene programs to spatial vibrational-biochemical states, RamanOmics provides a general framework and resource for scalable, multimodal profiling of cellular states.

systems biology↗

bioRxiv2025

Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology

The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimers disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1,196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. Mechanistically, ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3{beta} inhibition. Together, our study links ImP to hallmarks of neurodegeneration and suggest that targeting ImP may represent a potential strategy to modify ADRD risk.

pathology↗

bioRxiv2024

Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into de novo large cerebral infarction

It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia, without progressing to cerebral infarction, in mice, yet leads to a wide variety of outcomes (ranging from asymptomatic to death) in humans. We hypothesized that inhibition of NOS both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. In support, intraperitoneal administration of N{omega}-nitro-L-arginine methyl ester (L-NAME) followed by UCAO induced large-arterial infarction in mice, unlike UCAO alone. Six-hour laser-speckle-contrast imaging detected spreading ischemia in mice with infarction as assessed at 24h. In agreement with vasoconstriction/microthrombus formation shown by intravital microscopy, the NO-donor, molsidomine and the endothelial-NOS- activating antiplatelet, cilostazol, attenuated or prevented progression to infarction. Moreover, UCAO without L-NAME caused infarction in mice with hyperglycemia and hyperlipidemia, which, in turn, were associated with greater symmetric dimethylarginine (SDMA) levels. Further, increased levels of glucose and cholesterol associated with significantly larger infarct volumes in 438 consecutive patients with UCAO-mediated infarction. Lastly, Mendelian randomization identified a causative role of NOS inhibition, particularly in elevated SDMA concentration, in ischemic stroke risk. Therefore, NOS activity is a key factor determining the fate of hypoperfused brain following acute carotid occlusion, where SDMA could be a potential risk predictor.

neuroscience↗

bioRxiv2021

Raman2RNA: Live-cell label-free prediction of single-cell RNA expression profiles by Raman microscopy

Single cell RNA-Seq (scRNA-seq) and other profiling assays have opened new windows into understanding the properties, regulation, dynamics, and function of cells at unprecedented resolution and scale. However, these assays are inherently destructive, precluding us from tracking the temporal dynamics of live cells, in cell culture or whole organisms. Raman microscopy offers a unique opportunity to comprehensively report on the vibrational energy levels of molecules in a label-free and non-destructive manner at a subcellular spatial resolution, but it lacks in genetic and molecular interpretability. Here, we developed Raman2RNA (R2R), an experimental and computational framework to infer single-cell expression profiles in live cells through label-free hyperspectral Raman microscopy images and multi-modal data integration and domain translation. We used spatially resolved single-molecule RNA-FISH (smFISH) data as anchors to link scRNA-seq profiles to the paired spatial hyperspectral Raman images, and trained machine learning models to infer expression profiles from Raman spectra at the single-cell level. In reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs), R2R accurately (r>0.96) inferred from Raman images the expression profiles of various cell states and fates, including iPSCs, mesenchymal-epithelial transition (MET) cells, stromal cells, epithelial cells, and fibroblasts. R2R outperformed inference from brightfield images, showing the importance of spectroscopic content afforded by Raman microscopy. Raman2RNA lays a foundation for future investigations into exploring single-cell genome-wide molecular dynamics through imaging data, in vitro and in vivo.

genomics↗

bioRxiv2018

Concentration-dependent reduction of planktonic- and biofilm-state Vibrio alginolyticus by the bacteriophage pVa-21

There is an increasing emergence of antibiotic-resistant Vibrio alginolyticus, a zoonotic pathogen that causes mass mortality in aquatic animals as well as human infection; therefore, there is a demand for alternatives to antibiotics for treatment and prevention of infections caused by this pathogen. One possibility is through the exploitation of bacteriophages. In the present study, the bacteriophage pVa-21 belonging to Myoviridae, was isolated and characterized as a candidate biocontrol agent against V. alginolyticus. Its morphology, host range and infectivity, growth characteristics, planktonic or biofilm lytic property, stability under various conditions, and genome were investigated. Its latent period and burst size were estimated to be approximately 70 min and 58 plaque-forming units/cell, respectively. In addition, phage pVa-21 could inhibit bacterial growth both in the planktonic and biofilm state. Furthermore, phylogenetic and genome analyses revealed that the phage is closely related to phiKZ-like phages and can be classified as a new member of the phiKZ-like phages that infect bacteria belonging to the family Vibrionaceae.

microbiology↗