Biology subjects

Cho, G.

Publications and source records attributed to Cho, G..

13 recordsLinked to original sources

bioRxiv2026

Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function

Systemic inflammation is increasingly recognized as a key driver of neuroinflammation and cognitive dysfunction, particularly in the aging population. Yet, therapeutic interventions that broadly attenuate circulating inflammatory mediators without suppressing host immunity remain limited. Here, we report the development of taurine functionalized hyaluronic acid nanosponges (HA Tau) that blunt systemic inflammatory cascades to protect against downstream neurocognitive impairment. Using molecular docking calculations and experimental validations, we show that taurine functionalization enhances multivalent interactions with diverse cytokines, enabling broad-spectrum sequestration of inflammatory proteins from both murine and human plasma while preserving the intrinsic hypochlorous acid neutralizing ability of taurine. In aged mice undergoing orthopedic surgery, systemic administration of HA Tau nanosponges lowered the levels of circulating inflammatory mediators, preserved blood brain barrier integrity, and attenuated glial cell activation. These effects were accompanied by improved hippocampal neuronal activity and spatial working memory in mice. By dampening peripheral inflammatory surges, the nanosponges limit peripheral-to-central inflammatory signaling without directly targeting the central nervous system. Collectively, these findings demonstrate systemic inflammatory modulation could be an effective strategy for mitigating peripheral insult-induced neuroinflammation and cognitive decline, and position HA Tau nanosponges as a versatile biomaterial platform for treating inflammation-driven disorders.

bioengineering↗

bioRxiv2026

Patient-Specific Vascularized Lung Tumor Organoids for Tumor-Immune Profiling

The use of cellular systems to advance cancer therapeutics has expanded rapidly, spanning cell therapies to patient-specific tumor models. Platforms that recapitulate key features of the tumor microenvironment, including vascular and immune components, hold significant potential to improve the predictive power and translational relevance of preclinical models. Here, we report a vascularized tumor organoid platform that combines self-organizing microvascular networks with patient-derived tumor organoids and tumor-infiltrating lymphocytes. To minimize non-specific endothelial immunogenicity and enable broader compatibility across patient samples, we engineered the vasculature using {beta}2-microglobulin-knockout endothelial cells. Leveraging this system, we established patient-specific, lymphocyte-incorporated tumor models that enabled quantitative assessment of T cell infiltration. In conjunction with immune checkpoint blockade, this platform distinguishes responder and non-responder patient samples, consistent with the clinical observations. Single-cell RNA-sequencing revealed tumor-intrinsic and immune-associated programs underlying this stratification, identifying tumor-driven hyperangiogenic signaling as a barrier to T cell extravasation. Pharmacological co-targeting of PD1 and VEGF restored T cell infiltration in non-responder organoids, shifting them from an immune-excluded to an immune-inflamed state. Together, this vascularized tumor organoid platform provides a predictive and mechanistic framework for modeling patient-specific immunotherapy responses and design of combination therapies.

bioengineering↗

bioRxiv2026

Greater hypoxic burden predicts weaker gray matter-CSF coordination independent of non-hypoxic arousals: Implications for glymphatic activity

Study ObjectivesObstructive sleep apnea (OSA) is a risk factor for neurodegeneration, and glymphatic impairment may be one mechanistic pathway. Anti-phase coordination between brain pulsations and CSF flow, reflecting compensatory CSF displacement during each vascular pulsation cycle, supports glymphatic activity. This study examined whether hypoxic burden and sleep fragmentation, two distinct OSA pathologies, are differentially associated with brain pulsation-CSF flow dynamics. MethodsThis cross-sectional study included 28 individuals with newly identified OSA and 8 without OSA. Participants completed in-lab polysomnography or WatchPAT testing, providing measures of hypoxic burden, quantified as time below 90% oxygen saturation (T90), and non-hypoxic sleep fragmentation, quantified as respiratory effort-related arousals (RERAs). Participants also completed 7T resting-state functional MRI to estimate global BOLD-CSF, defined as anti-phase cross-correlation between blood-oxygen-level-dependent (BOLD) signal and CSF inflow. Associations were examined using correlation and hierarchical regression. Exploratory analyses examined region-specific BOLD-CSF and brain pulsation strength, quantified as BOLD amplitude. ResultsGreater T90 was associated with weaker global BOLD-CSF, independent of RERAs and covariates ({beta}=0.08,p=0.03). Greater T90 was also associated with higher BOLD amplitude across temporal, frontal, and parietal regions, but this elevation in amplitude was not accompanied by stronger region-specific BOLD-CSF coupling ({beta}=0.001,p>0.05). In contrast, among regions where BOLD amplitude was not associated with T90, greater BOLD amplitude predicted stronger region-specific BOLD-CSF ({beta}=-0.004,p<0.001). RERAs were not associated with global BOLD-CSF or BOLD amplitude. ConclusionsIn OSA, hypoxic burden may be the primary feature associated with impaired brain pulsation and CSF dynamics that support glymphatic activity. These alterations may be pronounced in the temporal lobe, where elevated pulsations were uncoupled from compensatory CSF displacement.

neuroscience↗

bioRxiv2025

In vivo bioreactor matures iPSC-CMs for MLP disease modeling

Muscle LIM protein (MLP) is a critical regulator of cardiomyocytes (CMs) cytoarchitecture, and its deficiency results in late-onset dilated cardiomyopathy (DCM) in both mice and human. However, recapitulating this phenotype in vitro using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been challenging largely due to their immature state. Here, we generated MLP knockout (MLP-KO) mouse iPSCs and differentiated them into CMs. We then employed both conventional in vitro and in vivo transplantation approach using immunocompromised rat hearts to promote cardiomyocytes maturation. Our results showed that while in vitro-matured MLP-KO iPSC-CMs failed to exhibit disease phenotypes, in vivo-matured MLP-KO iPSC-CMs successfully recapitulated the hallmarks of DCM, including disrupted sarcomeric architecture and upregulation of atrial natriuretic peptide (ANP), closely mirroring disease progression observed in MLP-deficient mice. These findings demonstrate that the in vivo maturation environment is essential for the maturation of iPSC-derived cardiomyocytes to better model genetic cardiac diseases like DCM and provide valuable insights for future therapeutic strategies.

bioengineering↗

bioRxiv2025

APOE4 homozygotes have less sleep fragmentation in late adulthood

Background and ObjectivesAPOE4, a genetic risk factor for Alzheimers Disease (AD), is associated with reduced functional connectivity of brain regions that regulate sleep, which may predispose persons to AD via altering sleep architecture. However, little is known about differences in sleep architecture by APOE genotype. MethodsThis cross-sectional study examined the association between APOE genotype and sleep architecture among middle-aged and older adults, using polysomnography (Sleep Heart Health Study, N=3,132). APOE genotype included: APOE4 heterozygotes, APOE4 homozygotes, APOE2 carriers, and APOE3 homozygotes. Macro sleep architecture was quantified using the percentage of time spent in rapid eye movement sleep (%REM), N1 (N1%), N2 (%N2), N3 (%N3), and arousal index. Micro sleep architecture was quantified as odds ratio product (ORP; a continuous measure of sleep depth) for overall sleep and each sleep stage, and spindle characteristics (power, density, and frequency). Linear regression was used, adjusting for covariates. ResultsThe mean age was 67, 53 percent were female, 24% were APOE4 heterozygotes, 2% were APOE4 homozygotes, 14% were APOE2 carriers, and 60% were APOE3 homozygotes. Macro sleep architecture did not vary across genotypes. Compared with APOE3 homozygotes, APOE4 homozygotes exhibited fewer arousals with age ({beta}=-0.33 per hour/year, p=0.04), resulting in significantly fewer arousals at age 70+. ORP decreased in a dose-response pattern with the number of APOE4 alleles during overall sleep and across all sleep stages (ORPAPOE3/3=0.94, ORPAPOE3/4=0.91, ORPAPOE4/4=0.87), and these group difference widened with each year of age. Finally, there was a trend for lower spindle density and power in APOE4 homozygotes relative to APOE3 homozygotes (ps=0.06). ConclusionsArousal threshold increased in a dose-response manner with each APOE4 allele, as evidenced by the findings on ORP. The differences in ORP between APOE3 homozygotes and APOE4 carriers widened further with age, paralleling age-related declines in arousal index among APOE4 homozygotes. Despite these indications of elevated arousal thresholds that might suggest less sleep fragmentation in APOE4 carriers, APOE4 homozygotes exhibited poorer sleep micro architecture, including trends toward reduced sleep spindle activity. Taken together, reduced arousability in APOE4 carriers may reflect abnormalities in cortical activation that blunt arousal rather than an indicator of healthier sleep.

physiology↗

bioRxiv2025

Basal forebrain volume is associated with cortical amyloid burden in cognitively unimpaired older adults at varying genetic risk for Alzheimers disease

BackgroundIn mild cognitive impairment and dementia due to Alzheimers disease (AD), postmortem and in vivo neuroimaging studies have demonstrated significant neuronal loss in the basal forebrain cholinergic system (BFCS), which provides the primary cholinergic input to the cerebral cortex. Within this region, atrophy is most prominent in the nucleus basalis of Meynert (nbM), a group of posteriorly clustered magnocellular neurons in the BFCS. However, less is known surrounding the relationship between amyloid deposition, BFCS atrophy, and medial temporal lobe (MTL) volume loss in the preclinical stages of AD. The current study investigates the relationship between sub-structural BFCS volume and cortical A{beta} burden in cognitively unimpaired middle-aged individuals at varying genetic risk for AD. MethodsCognitively unimpaired participants aged 50-65 with a first-degree family history for AD were genetically screened to select three groups: APOE genotype {varepsilon}4{varepsilon}4 (n=15), {varepsilon}3{varepsilon}4 (n=15), and {varepsilon}3{varepsilon}3 (n=15), matched for age and sex. Participants underwent imaging with [11C]PiB PET and structural 3T MRI. Distribution volumes ratios (DVR) with a whole cerebellum reference region were calculated for [11C]PiB PET analyses. BFCS sub-structural volumes were obtained from the SPM8 Anatomy Toolbox (Cholinergic nuclei [Ch] 1-3, Ch4). MTL subregional volumes (entorhinal cortex, hippocampus, amygdala, parahippocampal gyrus) were extracted using Freesurfer. ResultsBFCS amyloid burden was highest among APOE {varepsilon}4 homozygotes (Ch1-3, F(2, 42)=3.26, P=0.048; Ch4, F(2, 42)=3.82, P= 0.03). Ch4 (nbM), but not Ch1-3 volume, was found to be inversely associated with global A{beta} burden (Pearson r=-0.40, P=0.007). MTL subregional volumes were not associated with global A{beta} burden in the pooled sample. Exploratory analyses in groups stratified by amyloid positivity demonstrated reduced Ch4 volume (P=0.032) and significant inverse associations between Ch4 volume and amyloid burden (Pearson r = -0.70, P=0.02) in A{beta}+ participants. ConclusionsWe observed nbM (Ch4), but not MTL volume, to be significantly inversely associated with cortical amyloid burden in cognitively unimpaired, A{beta}+, middle-aged adults at varying genetic risk for AD. These findings provide further in vivo evidence suggesting that nbM atrophy is an early structural correlate of AD pathogenesis, potentially preceding MTL atrophy.

neuroscience↗

bioRxiv2025

Anxiety-associated behaviors following ablation of Miro1 from cortical excitatory neurons

Autism spectrum disorder, schizophrenia, and bipolar disorder are neuropsychiatric disorders that manifest early in life with a wide range of phenotypes, including repetitive behavior, agitation, and anxiety (American Psychological Association, 2013). While the etiology of these disorders is not completely understood, recent data implicate a role for mitochondrial dysfunction. To function optimally mitochondria must translocate to metabolically active intracellular compartments to support energetics and free-radical buffering; failure to achieve this localization results in cellular dysfunction (Picard et al., 2016). Mitochondrial Rho-GTPase 1 (Miro1) resides on the outer mitochondrial membrane and participates in neuronal microtubule-mediated mitochondrial motility and homeostasis (Fransson et al., 2003). Previous research implicates the loss of MIRO1 as a contributor to the onset/progression of neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimers disease, and Parkinsons disease (Kay et al., 2018). We have hypothesized that MIRO1 also has a role in nervous system development and function (Lin-Hendel et al., 2016). To test this, we ablated Miro1 from cortical excitatory progenitors by crossing floxed Miro1 mice with Emx1-cre mice. We found that mitochondrial mis-localization in migrating excitatory neurons was associated with reduced brain weight, decreased cortical volume, and subtle disruptions in cortical organization. Adult Miro1 conditional mutants exhibit agitative-like behaviors, including decreased nesting behavior and abnormal home cage activity. Open field testing revealed anxiety-like behavior and elevated plus maze and wide/narrow box testing found the mice avoided confined spaces. Our data link MIRO1 function with mitochondrial dynamics in the pathogenesis of several neuropsychiatric disorders and implicate mitochondrial localization in anxiety-like behaviors. SignificanceNeuropsychological disorders such as autism spectrum disorder, schizophrenia, and bipolar disorder have overlapping symptoms and behaviors. While the mechanisms underlying these disorders are not completely understood, recent evidence suggests mitochondrial dysfunction and mis-localization within a cell could play a role. Mitochondria are organelles that provide energy and other self-regulating processes to the cell. Previous research from our lab has shown distinct dynamic localization patterns within migrating excitatory and inhibitory neurons may be important during development. To further examine the importance of mitochondrial localization, we ablated MIRO1, a protein important for coupling mitochondria to motor proteins, in excitatory neurons. Mitochondria mis-localize in migrating excitatory neurons, and this is associated with a loss of motor skills and anxiety-like behavior in post-natal mice.

neuroscience↗

bioRxiv2025

Lower slow wave sleep and rapid eye-movement sleep are associated with brain atrophy of AD-vulnerable regions

Study objectivesSleep deficiency is associated with Alzheimers disease (AD) pathogenesis. We examined the association of sleep architecture with anatomical features observed in AD: (1) atrophy of hippocampus, entorhinal, inferior parietal, parahippocampal, precuneus, and cuneus regions ("AD-vulnerable regions") and (2) cerebral microbleeds. MethodsIn 271 participants of the Atherosclerosis Risk in the Communities Study, we examined the association of baseline sleep architecture with anatomical features identified on brain MRI 13[~]17 years later. Sleep architecture was quantified as the proportion of slow wave sleep (SWS), proportion of rapid eye-movement sleep (REM), and arousals index using polysomnography. Outcomes included (1) volumetric measurements of each AD-vulnerable region and (2) the presence of any cerebral microbleeds (CMBs) and that of lobar CMBs, which are more specifically associated with AD. We analyzed the association of each sleep predictor with each MRI outcome, adjusting for covariates. ResultsHaving less SWS was associated with smaller inferior parietal region ({beta}=-44.19 mm3 [95%CI=-76.63,-11.76]) and cuneus ({beta}=-11.99 mm3 [-20.93,-3.04]) after covariate adjustment. Having less REM was associated with smaller inferior parietal region ({beta}=-75.52 mm3 [-129.34, -21.70]) and precuneus ({beta}=-31.93 mm3 [-63.79,-0.07]). After FDR adjustments, lower SWS and REM, respectively, were associated with smaller inferior parietal region. Arousal index was not associated with the volumes of AD-vulnerable regions. None of the sleep architecture variables were associated with CMBs or lobar CMBs. ConclusionsSleep deficiency is associated with the atrophy of the inferior parietal region, which is observed in early AD. Sleep architecture may be a modifiable risk factor for AD. Brief summarya. Current Knowledge/Study Rationale: two sentences summarizing why the study was doneWhile impaired sleep architecture has been associated with Alzheimers disease [AD] diagnosis and cognitive decline. To better understand the impact of sleep on AD pathogenesis, this study examined the association of sleep architecture with anatomical features observed in AD, including the atrophy of AD-vulnerable regions and CMBs. b. Study Impact: two sentences summarizing how the study impacts the fieldOur study shows that lower slow wave sleep and rapid eye movement sleep may be precipitating factors of inferior parietal region atrophy, which is associated with AD risk. Importantly, the current studys findings can help characterize underlying mechanisms of how sleep deficiency, a prevalent disturbance among middle-aged and older adults, may facilitate AD pathogenesis and cognitive impairment.

neuroscience↗

bioRxiv2024

ARX regulates interneuron subtype differentiation and migration

Mutations in aristaless-related homeobox (ARX) are associated with neurodevelopmental disorders including developmental epilepsies, intellectual disabilities, and autism spectrum disorders, with or without brain malformations. Aspects of these disorders have been linked to abnormal cortical interneuron (cIN) development and function. To further understand ARXs role in cIN development, multiple Arx mutant mouse lines were interrogated. We found that ARX is critical for controlling cIN numbers and distribution, especially, in the developing marginal zone (MZ). Single cell transcriptomics and ChIP-seq, combined with functional studies, revealed ARX directly or indirectly regulates genes involved in proliferation and the cell cycle (e.g., Bub3, Cspr3), fate specification (e.g., Nkx2.1, Maf, Mef2c), and migration (e.g., Nkx2.1, Lmo1, Cxcr4, Nrg1, ErbB4). Our data suggest that the MZ stream defects primarily result from disordered cell-cell communication. Together our findings provide new insights into the mechanisms underlying cIN development and migration and how they are disrupted in several disorders.

neuroscience↗

bioRxiv2023

An ancestral vaccine induces anti-Omicron antibodies by hypermutation

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyzed blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyzed their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) was achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counter protective mechanism against virus variant immune escape.

bioengineering↗

bioRxiv2022

Arginine 65 methylation of Neurogenin 3 by PRMT1 is a prerequisite for development of hESCs into pancreatic endocrine cells

In the developing pancreas, Neurogenin 3 (NGN3) is a key transcription factor in the cell fate determination of endocrine progenitors (EPs). Although the activation and stability of NGN3 are regulated by phosphorylation, the role of arginine methylation of NGN3 is poorly understood. Here, we report arginine 65 methylation of NGN3 is absolutely required for the pancreatic lineage development of human embryonic stem cells (hESCs) in vitro. First, we found inducible protein arginine methyltransferase 1 (PRMT1)-knockout (P-iKO) hESCs did not differentiate from EPs to endocrine cells (ECs) in the presence of doxycycline. Loss of PRMT1 caused an accumulation of NGN3 in the cytoplasm of EPs and blocked NGN3s transcriptional activity in PRMT1-KO EPs. We also found that PRMT1 specifically methylates NGN3 arginine 65, and this modification is a prerequisite for ubiquitin-mediated NGN3 degradation. Our findings indicate arginine 65 methylation of NGN3 is a key molecular switch in hESCs in vitro permitting the differentiation into pancreatic endocrine lineages.

developmental biology↗

bioRxiv2020

Identification of select G-protein coupled receptors as regulators of the ER-mitochondria contact by drug screening

Interactions between the endoplasmic reticulum (ER) and mitochondria (Mito) are crucial for many cellular functions, and their interaction levels change dynamically depending on the cellular environment. Little is known about how the interactions between these organelles are regulated within the cell. Here we screened a compound library to identify chemical modulators for ER-Mito contacts. Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors ({beta}-ARs) in particular, scored in this screen. Analyses in multiple orthogonal assays validated that GPCR activation promotes physical and functional interactions between the two organelles. Furthermore, we have elucidated potential downstream effectors mediating GPCR-induced ER-Mito contacts. Given the role of GPCRs in sensing various extracellular signals and subsequently eliciting appropriate cellular responses, our data provide significant insights into the roles of ER-Mito contacts in maintaining cellular homeostasis and in responding to physiological demands or stresses.

cell biology↗

bioRxiv2017

Molecular genetic diversity of donkey (Equus asinus) in South Korea

The research on domestic donkey has little information and criteria comparing to other livestock, companion animal in South Korea. We analyzed genetic database of domestic donkey using microsatellite marker to clarify domestic donkey identification and paternity test. It is the first microsatellite marker analysis on domestic donkey in South Korea. We studied 179 horse samples from 50 Thoroughbred, 50 Jeju Halla horse, including 79 donkeys then analyzed 15 microsatellite marker (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10, LEX3 and VHL20). We observed genetic diversity from biostatic analysis of them.\n\nThe number of alleles on total average is 6.08 observed from 1 (ASB17), 2 (HMS1) to 14 (AHT5). The observed heterozygosity (OHet) is from 0.0000 (ASB17, HMS1) to 0.8608 (ASB23) which is mean value of 0.4861, the expected heterozygosity (EHet) is from 0.0000 (CA425) to 0.9104 (AHT5) with mean value of 0.5915, and the Polymorphism Information Content (PIC) on each group of microsatellite marker is from 0.0000 (ASB17) to 0.8968 (AHT5) observed as a mean value of 0.5374. Among 15 markers AHT4, AHT5, ASB23, CA425, HMS2, HMS3, HTG4, HTG10, LEX3 is observed above 5.000.\n\nThe results on 15 microsatellite marker analysis of 3 horse groups is that the donkey had 0.5915 EHet, 0.4861 OHet on average, Thoroughbred had 0.6721 EHet, 0.6587 OHet on average, and the Jeju halla horse had 0.7898 EHet, 0.7093 OHet on average observed. Furthermore the mean alleles value is observed as 6.08, 4.83, 8.00 in donkey, Thoroughbred, Jeju halla horse breed in each.

genetics↗