Search bioRxiv⌕ Search

Biology subjects

Vu, T.

Publications and source records attributed to Vu, T..

At least 19 recordsLinked to original sources
bioRxiv2026

Whole-body Super-resolution Functional and Molecular Imaging with Panoramic Photoacoustic-Ultrasound Tomography

Photoacoustic (PA) and ultrasound (US) imaging provide complementary molecular, functional, and anatomical contrasts. Here, we present a panoramic PA-US imaging platform that integrates multispectral PA computed tomography (PACT) along with reflection-mode and transmission-mode US imaging through a single shared full-ring ultrasound array. We employ an ultrafast planewave transmission scheme in reflection-mode US for power Doppler (PWD) imaging and ultrasound localization microscopy (ULM). Additionally, we use the transmission-mode US to reconstruct a spatially resolved speed of sound (SoS) map that corrects both PA and US reconstruction. Such correction sharpens the resolution of PACT, suppresses the artifacts of PWD, and improves microbubble localization of ULM. Elevational scanning further enables whole-body volumetric imaging with co-registered PA and US contrasts. The integrated system maps photoswitchable DrBphP1-expressing tumors alongside their blood perfusion and oxygenation environment. Applying the platform to monitor unilateral renal ischemia-reperfusion injury, we report that microvascular perfusion and renal oxygenation recover at different rates. Collectively, we demonstrate that the integrated PA-US imaging platform provides a unified framework for multiparametric study of anatomy, perfusion, microvascular flow, oxygenation, and molecular activities.

bioengineering↗
bioRxiv2026

Dynamic hybrid-hydrogel lung models decouple matrix composition, stiffness, and fibroblast memory to define distinct drivers of fibrotic progression

Idiopathic pulmonary fibrosis is a devastating chronic lung disease characterized by progressive scarring of the lung, which leads to impaired gas exchange and ultimately death. While research has provided us with extensive understanding on end-stage disease, the factors that lead to forward-feedback loops of fibrotic progression are still not fully known. Cell intrinsic activation, pathological extracellular matrix (ECM) composition, and increased tissue stiffness are all hallmarks of advanced fibrosis, but the relative contribution of these factors to disease has been difficult to disentangle using classic in vivo models. In this study we created biomaterials-based 3D lung models that incorporate geometrically relevant co-culture of lung epithelial cells and fibroblasts with tunable stiffness, ECM-containing hybrid-hydrogels. Using this model system, we demonstrated that environmental stiffness has the strongest effect on overall fibroblast activation. RNAseq analysis revealed unique gene-level changes in both fibroblasts and epithelial cells due to both composition and stiffness, highlighting the importance of incorporating both factors into any in vivo disease models. Overall, these results reinforce the value of biomaterials-based models in understanding disease pathogenesis, and their potential for screening of treatment responses.

bioengineering↗
bioRxiv2026

Serpin-Driven Green Camouflage and NIR Fluorescence in Frogs

Animals have evolved multiple strategies to generate optical traits and coloration. While most amphibians rely on a three-dimensional arrangement of chromatophores in the skin, hundreds of arboreal frog species achieve leaf-like green color through a different mechanism involving reduced pigmentation, subcutaneous biological mirrors, and high concentrations of the blood-derived pigment biliverdin. Although biliverdin is rapidly excreted in most vertebrates, hylid and centrolenid frogs can retain it through the binding to a serpin-family protein (BBS). Here we show that BBSs bind biliverdin with high affinity (Kd < 10 nM), comparable to hormone-receptor interactions. This interaction alters biliverdins spectral signature in ways that resemble those of green-leaf pigments. BBSs from different species exhibit distinct biophysical properties, accounting for interspecific differences in color saturation and hue. Unlike most serpins in vivo, BBS of the glassfrog Teratohyla pulverata is naturally cleaved, yielding a highly thermostable, thermodynamically favored protein, without loss of affinity. Using custom-designed hyperspectral photoacoustic tomography (PAT), we demonstrate that BBS is widely distributed throughout the body, contributing to whole-body color and camouflage. Furthermore, we show that BBSs emit near-infrared (NIR) fluorescence (>700 nm) rendering these frogs fluorescent in a spectral region where biological tissues are largely transparent. Together, BBSs shed light on serpin evolution, protein thermostability, amphibian color diversity, and the development of NIR molecular probes.

biochemistry↗
bioRxiv2026

Appearance of Amyloid-β Early in Life Initiates Neuronal Hyper-excitability, Mitochondrial Decay, and Loss of Dendritic Complexity in the Hippocampal CA1 Region of 5xFAD Mice

Alzheimers disease (AD) is characterized by progressive cognitive decline and stereotyped neuropathology, yet the earliest cellular events that precede overt plaque burden and measurable behavioral impairment remain incompletely defined. Here, we tested the hypothesis that synaptic hyperexcitability and subcellular metabolic dysfunction emerge early in the 5xFAD mouse model and contribute to region-specific neuronal vulnerability before substantial amyloid plaque deposition. Using the 5xFAD heterozygous mouse, we first established the onset of transgene expression and the timing of plaque accumulation. Robust transgene expression was detected by postnatal day 15 and significant plaque accumulation by 4 months of age. Ex vivo electrophysiology revealed an early hyperexcitable phenotype at 1 month of age, including both increased AMPA receptor-mediated transmission and N-methyl-D-aspartate receptor signaling associated with the GluN2B subunit. Given the tight coupling between glutamatergic hyperactivity, calcium dysregulation, and mitochondrial health, we assessed mitochondrial structure and function at this pre-plaque stage. Mitochondrial abnormalities consistent with impaired bioenergetic homeostasis were evident. Morphological analyses further demonstrated that these early changes were associated with altered dendritic architecture in the CA1 and dentate gyrus regions, revealing hippocampal subregional susceptibility. Finally, spatial transcriptomics supported this anatomical selectivity by identifying regionally enriched molecular signatures consistent with differential vulnerability. The CA1 region exhibited more reductions in mitochondria-related transcripts than CA3 or dentate gyrus and these reductions were specifically associated with CA1 pyramidal cell neurons. Together, these findings define a pre-plaque window in 5xFAD mice marked by GluN2B-linked glutamatergic hyperexcitability, early mitochondrial disruption, and selective dendritic and transcriptional vulnerability across hippocampal subregions. This integrated timeline suggests that synaptic and metabolic dysfunctions arise before substantial plaque deposition and may represent tractable early targets for intervention aimed at delaying or preventing downstream neurodegeneration in AD.

neuroscience↗
bioRxiv2025

Real-Time Viability Assessment of Ex Vivo Mouse Kidneys for Transplant Applications Using Dynamic Optical Coherence Tomography

Kidney transplantation remains the preferred treatment for patients with end-stage kidney disease. However, the ongoing shortage of donor organs continues to limit the availability of transplant treatments. Existing evaluation methods, such as the kidney donor profile index (KDPI) and pre-transplant donor biopsy (PTDB), have various limitations, including low discriminative power, invasiveness, and sampling errors, which reduce their effectiveness in organ quality assessment and contribute to the risk of unnecessary organ discard. In this study, we explored the dynamic optical coherence tomography (DOCT) as a real-time, non-invasive approach to monitor the viability of ex vivo mouse kidneys during static cold storage over 48 hours. The dynamic metrics logarithmic intensity variance (LIV), early OCT correlation decay speed (OCDSe), and late OCT correlation decay speed (OCDSl) were extracted from OCT signal fluctuations to quantify temporal and spatial tissue activity and deterioration. Our results demonstrate that DOCT provides complementary functional information to morphological assessment offered by conventional OCT imaging, showing potential to improve pre-transplant organ evaluation and clinic decision-making.

bioengineering↗
bioRxiv2025

Netrin-1 regulates colorectal cancer stem cell self-renewal via a TFF3 dependent paracrine survival mechanism

BackgroundMetastatic colorectal cancer (mCRC) is associated with high recurrence rates and resistance to conventional treatments, largely driven by cancer stem cells (CSCs) that contribute to tumor progression and therapeutic evasion. This study aims to investigate the role of netrin-1 and its dependence receptor UNC5B in regulating CSC self-renewal in mCRC and explore their potential as therapeutic targets. MethodsWe used patient-derived liver metastasis organoids (PDOs) to examine the effects of netrin-1 on CSC self-renewal. The role of UNC5B was evaluated by silencing its expression using CRISPR and assessing the impact on CSC apoptosis in response to an anti-netrin-1 blocking antibody (NP137) using extreme limiting dilution assays (ELDAs). Single-cell RNA sequencing was employed to explore the molecular mechanisms behind netrin-1/UNC5B regulation of CSC fate. Clinical data from a patient with mCRC were used to validate the findings. ResultsNetrin-1 promoted CSC self-renewal by inhibiting apoptosis, a process reversed by NP137. UNC5B was identified as the primary receptor mediating this effect, as its silencing eliminated Netrin-1-induced self-renewal. Trefoil Factor 3 (TFF3), secreted by UNC5B-expressing cells, plays a key role in netrin-1-induced CSC self-renewal. Clinical trial data from a patient with mCRC showed a reduction in TFF3 and stemness genes expression after treatment with NP137. Furthermore, combining NP137 with FOLFOX chemotherapy enhanced cell death and inhibited tumor growth in PDO xenograft models. ConclusionThis study identifies the netrin-1/UNC5B/TFF3 axis as a critical regulator of CSC self-renewal in mCRC and suggests that targeting this pathway with NP137, in combination with chemotherapy, could provide a promising therapeutic approach for mCRC patients.

cancer biology↗
bioRxiv2025

Fluphenazine, an antipsychotic compound, ameliorates Alzheimer's disease by clearing amyloid beta accumulation in

The ageing population worldwide faces an increasing burden of age-related conditions, with Alzheimers disease being a prominent neurodegenerative concern. Drug repurposing, the practice of identifying new therapeutic applications for existing drugs, offers a promising avenue for accelerated intervention. In this study, we utilized the yeast S. cerevisiae to screen a library of 1,760 FDA-approved compounds, both with and without rapamycin, to assess potential synergistic effects on yeast growth. We identified 87 compounds that showed synergistic effect with rapamycin and caused growth defects in yeast. These compounds were further screened for their effects on paralysis in a C. elegans model of Alzheimers disease. We found that three compounds synergistically delayed paralysis in combination with rapamycin. Additionally, four other compounds delayed paralysis when tested at different concentrations. Moreover, we tested fluphenazine, an antipsychotic drug identified in our screen and found that it enhanced the overall health of treated worms. Western blot and X-34 staining confirmed that fluphenazine reduced amyloid-beta accumulation. These results indicate that repurposed drugs have significant potential to accelerate Alzheimers disease drug discovery.

molecular biology↗
bioRxiv2025

On-Body Measure of Reaction Time Correlates With Intoxication Level

Excessive alcohol use has profound effects on individual health and healthcare systems worldwide. Despite this, there is currently no system or device that can detect robustly the physiologic and functional effects of alcohol-based impairment in real-world conditions. A practical, on-body, device capable of rapidly and accurately determining the functional capacity of an individual to drive, before they can start the ignition of the automobile, is required. The goal of this pilot study was to evaluate the effect of acute alcohol intoxication on premotor time (PMT) and reaction time (RT), both highly sensitive of individual cognition, as evaluated by the Pison Technology wrist-worn wearable. Nineteen participants were included in the study, 14 subjects who consumed alcohol sufficient to raise blood alcohol concentration (BAC) to 0.12% within a 30-minute period and 5 controls who did not consume alcohol. Changes in reaction time data were correlated with blood alcohol levels as measured by breathalyzer testing, identifying a statistically significant difference between those participants under the legal limit and those over the legal limit. Both group and individual analyses confirmed that as the BAC increased in subjects, the PMT also increased. The PMT also decreased as the BAC returned to levels under the legal intoxication threshold (0.08%). A significant effect of BAC levels on changes in PMT at the p < 0.05 level for two conditions. This study demonstrated the first use case of an on-body, neuro-physiological sensor capable of detecting sensitive changes of reaction time, in real time, that serves as an easy-to-measure proxy for blood alcohol content and impairment.

neuroscience↗
bioRxiv2024

Advanced deep-tissue imaging and manipulation enabled by biliverdin reductase knockout.

We developed near-infrared (NIR) photoacoustic and fluorescence probes, as well as optogenetic tools from bacteriophytochromes, and enhanced their performance using biliverdin reductase-A knock-out model (Blvra-/-). Blvra-/- elevates endogenous heme-derived biliverdin chromophore for bacteriophytochrome-derived NIR constructs. Consequently, light-controlled transcription with IsPadC-based optogenetic tool improved up to 25-fold compared to wild-type cells, with 100-fold activation in Blvra-/- neurons. In vivo, light-induced insulin production in Blvra-/- reduced blood glucose in diabetes by [~]60%, indicating high potential for optogenetic therapy. Using 3D photoacoustic, ultrasound, and two-photon fluorescence imaging, we overcame depth limitations of recording NIR probes. We achieved simultaneous photoacoustic imaging of DrBphP in neurons and super-resolution ultrasound localization microscopy of blood vessels [~]7 mm deep in the brain, with intact scalp and skull. Two-photon microscopy provided cell-level resolution of miRFP720-expressing neurons [~]2.2 mm deep. Blvra-/- significantly enhances efficacy of biliverdin-dependent NIR systems, making it promising platform for interrogation and manipulation of biological processes.

cell biology↗
bioRxiv2024

cytoKernel: Robust kernel embeddings for assessing differential expression of single cell data

High-throughput sequencing of single-cell data can be used to rigorously evlauate cell specification and enable intricate variations between groups or conditions. Many popular existing methods for differential expression target differences in aggregate measurements (mean, median, sum) and limit their approaches to detect only global differential changes. We present a robust method for differential expression of single-cell data using a kernel-based score test, cytoKernel. cytoKernel is specifically designed to assess the differential expression of single cell RNA sequencing and high-dimensional flow or mass cytometry data using the full probability distribution pattern. cytoKernel is based on kernel embeddings which employs the probability distributions of the single cell data, by calculating the pairwise divergence/distance between distributions of subjects. It can detect both patterns involving aggregate changes, as well as more elusive variations that are often overlooked due to the multimodal characteristics of single cell data. We performed extensive benchmarks across both simulated and real data sets from mass cytometry data and single-cell RNA sequencing. The cytoKernel procedure effectively controls the False Discovery Rate (FDR) and shows favourable performance compared to existing methods. The method is able to identify more differential patterns than existing approaches. We apply cytoKernel to assess gene expression and protein marker expression differences from cell subpopulations in various publicly available single-cell RNAseq and mass cytometry data sets. The methods described in this paper are implemented in the open-source R package cytoKernel, which is freely available from Bioconductor at http://bioconductor.org/packages/cytoKernel.

bioinformatics↗
bioRxiv2024

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. This strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating host brain environment influences on interneuron progenitors as they integrate is critical to optimizing this strategy across different disease states. Here, we systematically evaluated age and brain region influences on survival, migration and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to juvenile or adult. MGE progenitors migrate more widely in cortex compared to hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into dentate gyrus sub-region of early postnatal hippocampus can differentiate into astrocytes. Our results suggest that host brain environment critically regulates survival, spatial distribution and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.

neuroscience↗
bioRxiv2023

SmCCNet 2.0: an Upgraded R package for Multi-omics Network Inference

SummarySparse multiple canonical correlation network analysis (SmCCNet) is a machine learning technique for integrating omics data along with a variable of interest (e.g., phenotype of complex disease), and reconstructing multi-omics networks that are specific to this variable. We present the second-generation SmCCNet (SmCCNet 2.0) that adeptly integrates single or multiple omics data types along with a quantitative or binary phenotype of interest. In addition, this new package offers a streamlined setup process that can be configured manually or automatically, ensuring a flexible and user-friendly experience. AvailabilityThis package is available in both CRAN: https://cran.r-project.org/web/packages/SmCCNet/index.html and Github: https://github.com/KechrisLab/SmCCNet under the MIT license. The network visualization tool is available at https://smccnet.shinyapps.io/smccnetnetwork/.

bioinformatics↗
bioRxiv2023

High dimensional analyses reveal activation of lymphocyte subsets and reversal of immunoresistance by cytokine enhancement of adoptive cellular vaccine therapy in prostate cancer.

Engineered cell therapies have emerged as a potent therapeutic option for the hematologic malignancies, however solid tumor responses to similar approaches have been modest. The outlier is Sipuleucel-T (sip-T), an FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report the first high dimensional cellular analyses of sip-T using mass cytometry (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median [~]60%) of sip-T, followed by B-cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate cancer. Of cytokines tested, IL-15 treated sip-T showed the most significant activation and proliferation of effector lymphocytes, as well as augmentation of tumor cytotoxicity in vitro. Co-culture of sip-T with IL-15 and control or prostate-relevant antigens showed significant activation and expansion of CD8 T and NKT cells in an antigen-specific manner. Adoptive transfer of IL-15 treated sip-T into NSG mice resulted in potent prostate tumor growth inhibition compared with control sip-T. Evaluation of tumor-infiltrating lymphocytes revealed a 2 to 14-fold higher influx of sip-T and a significant increase in interferon (IFN)-{gamma} producing CD8+ T and NKT cells within the tumor microenvironment (TME) in the IL-15 group. In conclusion, we put forward the first evidence that IL-15 treatment can enhance the functional anti-tumor efficacy of sip-T, providing rationale for combining IL-15 or IL-15 agonists with sip-T to treat mCRPC patients. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/550213v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@130adb0org.highwire.dtl.DTLVardef@db2567org.highwire.dtl.DTLVardef@174a953org.highwire.dtl.DTLVardef@18c049_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryIL-15 treatment can enhance the efficacy/anti-tumor immunity of sipuleucel-T by modulating CD8+ T-cell and CD56+ NKT subsets.

immunology↗
bioRxiv2023

SpaceANOVA: Spatial co-occurrence analysis of cell types in multiplex imaging data using point process and functional ANOVA

MotivationMultiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or tumor microenvironment (TME). Exploring the potential variations in the spatial co-occurrence or co-localization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. ResultsWe present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process (PPP) and functional analysis of variance (FANOVA). Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered in such a context due to the complex nature of the data-collection procedure. We demonstrate the superior statistical power and robustness of the method in comparison to existing approaches through realistic simulation studies. Furthermore, we apply the method to three real datasets on different diseases collected using different imaging platforms. In particular, one of these datasets reveals novel insights into the spatial characteristics of various types of precursor lesions associated with colorectal cancer. AvailabilityThe associated R package can be found here, https://github.com/sealx017/SpaceANOVA. Contactsealso@musc.edu Supplementary informationThe supplementary material is attached.

bioinformatics↗
bioRxiv2022

A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids

Organoids are powerful experimental models for studying the ontogeny and progression of diseases including cancer. Organoids are conventionally cultured in bulk using an extracellular matrix mimic. However, organoids in bulk culture physically overlap, making it impossible to track the growth of individual organoids over time in high throughput. Moreover, local spatial variations in bulk matrix properties make it difficult to assess whether observed phenotypic heterogeneity between organoids results from intrinsic cell differences or microenvironment variability. Here, we developed a microwell-based method that enables high-throughput quantification of image-based parameters for organoids grown from single cells, which can be retrieved from their microwells for sequencing and molecular profiling. Coupled with a deep-learning image processing pipeline, we characterized phenotypic traits including growth rates, cellular movement, and apical-basal polarity in two CRISPR-engineered human gastric organoid models, identifying genomic changes associated with increased growth rate and changes in accessibility and expression correlated with apical-basal polarity.

bioengineering↗
bioRxiv2022

FunSpace: A functional and spatial analytic approach to cell imaging data using entropy measures

Spatial heterogeneity in the tumor microenvironment (TME) plays a critical role in gaining insights into tumor development and progression. Conventional metrics typically capture the spatial differential between TME cellular architectures by either exploring the cell distributions in a pairwise fashion or aggregating the heterogeneity across multiple cell distributions without considering for the spatial contribution. As such, none of the existing approaches has fully accounted for the heterogeneity caused by both cellular diversity and spatial configurations of multiple cell categories. In this article, we propose an approach to leverage the spatial entropy measures at multiple distance ranges to account for the spatial heterogeneity across different cellular architectures. Then, functional principal component analysis (FPCA) targeting sparse data is applied to estimate FPC scores which are then predictors in a Cox regression model to investigate the impact of spatial heterogeneity in the TME on survival outcome, holding other clinical variables constant. Using an ovarian cancer dataset (n = 114) as a case study, we found that the spatial heterogeneity in the TME immune compositions of CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages, had a significant non-zero effect on the overall survival (p = 0.027). In the simulations studies under different spatial configurations, the proposed method demonstrated a high predictive power by accounting for both clinical effect and the impact of spatial heterogeneity.

bioinformatics↗