Biology subjects

Eom, H.

Publications and source records attributed to Eom, H..

4 recordsLinked to original sources

bioRxiv2026

Acute head shaking precedes chronic corpus callosum deficits during repeated cocaine exposure in common marmosets

Background: Stimulant exposure can induce acute stereotyped behaviors and chronic alterations in brain connectivity and white matter integrity. However, the temporal sequence and molecular changes linking these cocaine-induced phenotypes remain unclear. Methods: We combined LabGym-based behavioral analysis, longitudinal brain imaging, and cross-species molecular analysis in 11 common marmosets (Callithrix jacchus; seven male, four female): four underwent behavioral and imaging studies, six provided molecular data, and one provided immunohistochemical data. Male Cryab knockout and wild-type mice underwent functional studies. Results: Acute cocaine (5 mg/kg, intraperitoneally) induced rapid, repetitive lateral head movements, defined as head shaking. After 1 and 10 months of repeated exposure, resting-state functional connectivity was altered in sensory, parietal, prefrontal, motor, and hippocampal regions. Changes were detected at 1 month, whereas diffusion tensor imaging showed reduced fractional anisotropy and axial diffusivity in the corpus callosum splenium at 10 months, with no significant genu changes. Cross-species transcriptomic and proteomic comparison identified DPYSL2 and DNM3 as shared axon-associated molecules. Western blotting showed reduced DPYSL2 in brain tissue from cocaine-treated marmosets. CRYAB localized to O4-positive callosal oligodendrocytes and increased following chronic cocaine exposure. Cryab knockout mice had reduced corpus callosum thickness, increased forced-swim immobility, and reduced open-field distance traveled, supporting a role for CRYAB in corpus callosum integrity and depression-related behavior. Conclusions: These findings show that acute cocaine-induced stereotyped head shaking precedes functional connectivity changes and later corpus callosum deficits. Reduced DPYSL2 may be associated with axonal dysfunction, whereas increased CRYAB may represent a response to cocaine-induced white matter stress.

pharmacology and toxicology↗

bioRxiv2026

Restoration of circulating 2-arachidonoylglycerol levels attenuates cocaine self-administration through endocannabinoid-dopamine interactions in common marmosets

To date, no pharmacotherapy has been approved for cocaine use disorder. Endocannabinoid signaling is closely related to dopamine-dependent reinforcement and may regulate cocaine-related behaviors. In this study, we used common marmosets (Callithrix jacchus) to investigate whether 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid lipid, reduces cocaine reinforcement in a non-restraint oral self-administration model. Marmosets performed oral cocaine self-administration under a fixed-ratio 1 schedule, and cocaine intake was confirmed using plasma benzoylecgonine detection. Dopamine transporter (DAT)-related positron emission tomography (PET) signal, DAT and G protein-coupled receptor 55 (GPR55)-associated fluorescent signals, GPR55/DAT immunofluorescence, and synaptosomal dopamine responses were assessed using 18F-N-(3-fluoropropyl)-2{beta}-carboxymethoxy-3{beta}-(4-iodophenyl) nortropane (18F-FP-CIT) PET imaging, ex vivo fluorescent ligand imaging, confocal microscopy, and dopamine quantification. Marmosets acquired oral cocaine self-administration with preferential active lever responding. Repeated cocaine self-administration reduced striatal DAT-related 18F-FP-CIT PET signal in vivo. In striatal slices, cocaine decreased fluorescent false neurotransmitter (FFN102)-associated DAT signal and increased T1117-associated GPR55 signal. Systemic 2-AG pretreatment reduced cocaine self-administration while restoring diminished circulating 2-AG levels. GPR55 and DAT immunofluorescent signals were colocalized in marmoset brain sections, and 2-AG enhanced cocaine-induced dopamine elevation in synaptosomal preparations. Taken together, these findings suggest that 2-AG attenuates cocaine-taking behavior and may be associated with GPR55/DAT-related dopaminergic responses in common marmosets.

pharmacology and toxicology↗

bioRxiv2025

ATOMIC: A graph attention neural network for ATOpic dermatitis prediction on human gut MICrobiome

Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by complex interactions among genetic, environmental, and microbial factors; however, its etiology remains unclear. Recent studies have reported the role of gut microbiota dysbiosis in AD pathogenesis, leading to increased interest in microbiome-targeted therapeutic strategies such as probiotics and fecal microbiota transplantation. Building on these findings, recent advances in computational modeling have introduced machine learning and deep learning-based approaches to capture the nonlinear relationships between gut microbiota and diseases. However, these models focus on diseases other than AD and often fail to capture complex microbial interactions or incorporate microbial genomic information, thereby offering limited interpretability. To address these limitations, we propose ATOMIC, an interpretable graph attention network-based model that incorporates microbial co-expression networks to predict AD. Microbial co-expression networks incorporate microbial genomic information as node features, thereby enhancing their ability to capture functionally relevant microbial patterns. To train and test our model, we collected and processed 99 gut microbiome samples from adult patients with AD and healthy controls at Kangwon National University Hospital (KNUH). As a result, ATOMIC achieved an AUROC of 0.810 and an AUPRC of 0.927 on the KNUH dataset. Furthermore, ATOMIC identified microbes potentially associated with AD prediction and proposed candidate microbial biomarkers that may inform future therapeutic strategies. To facilitate future research, we publicly released a gut microbial abundance dataset from KNUH. The source code and processed abundance data are available from ATOMIC GitHub repository at https://www.github.com/KU-MedAI/ATOMIC. Author summaryAtopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 120 million people worldwide, often leading to a reduced quality of life, including sleep disturbances and stress. Current treatment methods rarely achieve complete remission, and the precise cause of AD remains unclear. The association between imbalances in the gut microbiota and the pathogenesis of AD has highlighted the gut microbiota as a promising target for therapeutic strategies. Exploring the potential role of the gut microbiota in modulating host immune responses is likely to have a positive impact on future AD treatment. Consequently, the growing need to develop machine learning and deep learning-based predictive models using gut microbiome data. However, existing models often suffer from limited interpretability owing to their black-box nature and frequently overlook microbial interactions and genomic contexts. To address these limitations, we propose a novel model called ATOMIC, which integrates microbial co-expression networks and genomic information to predict AD. Our model achieved superior performance in terms of AUROC, AUPRC, and F1 scores compared with existing models and provided interpretable insights through an attention mechanism, thereby offering promising potential for identifying relevant biomarkers. Together, these results highlight ATOMICs potential for the accurate prediction of AD and for identifying biologically meaningful microbial signatures.

systems biology↗

bioRxiv2024

Discovery of Highly Active Kynureninases for Cancer Immunotherapy through Protein Language Model

Overcoming the immunosuppressive tumor microenvironment is a promising strategy in anticancer therapy. L-kynurenine, a strong immunosuppressive metabolite can be degraded through kynureninases. Through homology searches and protein language models, we identified and then experimentally determined the efficacy of four top-ranked kynureninases. The catalytically most active one nearly doubles turnover number over the prior best, reducing tumor weight by 3.42 times in mouse model comparisons, and thus, presenting substantial therapeutic potential.

cancer biology↗