Biology subjects

Hung, J.

Publications and source records attributed to Hung, J..

7 recordsLinked to original sources

bioRxiv2026

MHCII+ cancer-associated fibroblasts promote antitumor immunity in pancreatic cancer

The functions of major histocompatibility complex class II molecule-expressing cancer-associated fibroblasts (MHCII+CAFs) in pancreatic cancer remain controversial. MHCII+CAFs are primarily described as immunosuppressive, as MHCII allows for direct interaction with, and support of, regulatory T cells (Tregs). However, MHCII+CAF functions may be more complex depending on their origins and their cellular interactions within the tumor microenvironment. Here, using orthotopic models of pancreatic cancer, we show that conventional CD4+ T cells and their production of Interferon gamma (IFN{gamma}) increased MHCII+CAFs in tumors. Acute depletion of Tregs using Foxp3DTR mice revealed that Tregs suppress the abundance of MHCII+CAFs in tumors by inhibiting CD4 T cell responses that can directly control primary tumor growth and metastatic progression. Functionally, MHCII expression on fibroblasts was required for CD4 T cell control of PDAC progression upon Treg ablation. Collectively, our findings identify an IFN{gamma}-driven, antitumor activity of MHCII expression on CAFs and reveal that CAFs may be harnessed to promote adaptive immunity to PDAC.

immunology↗

bioRxiv2025

Intratumoral Treg ablation is sufficient to mediate tumor control systemically without autoimmunity

Regulatory T cells (Tregs) infiltrate most tumors, yet whether they suppress immune responses directly within tumor tissues is not clear. We used intratumoral (IT) delivery of diphtheria toxin (DT) in Foxp3DTR mice to deplete IT Tregs while leaving peripheral Tregs intact. IT delivery of DT reduced Treg frequencies in the tumor, which promoted potent tumor control without autoimmunity. Interestingly, this control was principally mediated by CD4+ T cells, whereas CD8+ T cells only contributed when CD4+ T cells were absent. While conventional dendritic cells (cDCs) were required to clear tumors, Batf3+ cDC1s were dispensable. Distant secondary tumors, mimicking metastases, were also controlled by IT Treg ablation. Mechanistically, IT Tregs suppressed antitumor T cell responses by blocking the acquisition of tumor antigen by cDC2s. Importantly, similar mechanisms of control were observed using a clinically translatable IT Treg-depleting anti-CCR8 antibody and reveal a distinct therapeutic strategy that leverages cDC2s and CD4+ T cells.

cancer biology↗

bioRxiv2025

A single MHCII neoepitope mRNA vaccine elicits CD4 T- and B- cell responses promoting endogenous CD8 anti-tumor immunity

Recent progress in therapeutic cancer vaccines has shown promising clinical activity, especially when targeting MHC class I (MHCI) neoantigen-specific CD8+ T cell responses in post-surgical patients. To explore the role of CD4+ T cells in vaccine-dependent tumor rejection, we constructed an mRNA lipoplex vaccine encoding a single MHCII-restricted neoantigen. The vaccine elicited Tfh and Th1 cell responses while decreasing Tregs, leading to rejection of established tumors in mice. IL-21 and IFN-{gamma}, crucial for Tfh and Th1 function respectively, contributed to anti-tumor activity. B cells and neoantigen-specific antibodies were also shown to participate in vaccine efficacy. Additionally, conventional type 1 dendritic cells (cDC1s) were essential for eliciting vaccine-induced CD4+ T cells, and both cDC1s and CD4+ T cells were required to enhance endogenous CD8+ responses, which were crucial for tumor control. Our results suggest that immunizing against MHCII neoantigens alone is sufficient to orchestrate a potent and cooperative immune response against cancer.

immunology↗

bioRxiv2025

Alpha modulation of spiking activity across multiple brain regions in mice performing a tactile selective detection task

Many cognitive and sensory processes are characterized by strong relationships between the timing of neuronal spiking and the phase of ongoing local field potential oscillations. The coupling of neuronal spiking in neocortex to the phase of alpha oscillations (8-12 Hz) has been well studied in nonhuman primates but remains largely unexplored in other mammals. How this alpha modulation of spiking differs between brain areas and cell types, as well as its role in sensory processing and decision making, are not well understood. We used Neuropixels 1.0 probes to chronically record neural activity from somatosensory cortex, prefrontal cortex, striatum, and amygdala in mice performing a whisker-based selective detection task. We observed strong spontaneous alpha modulation of single-neuron spiking activity during inter-trial intervals while mice performed the task. The prevalence and strength of alpha phase modulation differed significantly across regions and between cell types. Phase modulated neurons exhibited stronger responses to both go and no-go stimuli, as well as stronger motor- and reward-related changes in firing rate, than their unmodulated counterparts. The increased responsiveness of phase modulated neurons suggests they are innervated by more diverse populations. Alpha modulation of neuronal spiking during baseline activity also correlated with task performance. In particular, many neurons exhibited strong alpha modulation before correct trials, but not before incorrect trials. These data suggest that dysregulation of spiking activity with respect to alpha oscillations may characterize lapses in attention.

neuroscience↗

bioRxiv2024

Piximi - An Images to Discovery web tool for bioimages and beyond

Deep learning has greatly accelerated research in biological image analysis yet it often requires programming skills and specialized tool installation. Here we present Piximi, a modern, no-programming image analysis tool leveraging deep learning. Implemented as a web application at Piximi.app, Piximi requires no installation and can be accessed by any modern web browser. Its client-only architecture preserves the security of researcher data by running all computation locally. Piximi offers four core modules: a deep learning classifier, an image annotator, measurement modules, and pre-trained deep learning segmentation modules. Piximi is interoperable with existing tools and workflows by supporting import and export of common data and model formats. The intuitive researcher interface and easy access to Piximi allows biological researchers to obtain insights into images within just a few minutes. Piximi aims to bring deep learning-powered image analysis to a broader community by eliminating barriers to entry.

cell biology↗

bioRxiv2020

Mapping glycan-mediated galectin-3 interactions by live cell proximity labeling

Galectin-3 is a glycan-binding protein (GBP) that binds {beta}-galactoside glycan structures to orchestrate a variety of important biological events, including the activation of hepatic stellate cells to cause hepatic fibrosis. While the requisite glycan epitopes needed to bind galectin-3 have long been elucidated, the cellular glycoproteins that bear these glycan signatures remain unknown. Given the importance of the three-dimensional arrangement of glycans in dictating GBP interactions, strategies that allow the identification of GBP receptors in live cells, where the native glycan presentation and glycoprotein expression are preserved, possess significant advantages over static and artificial systems. Here, we describe the integration of a proximity labeling method and quantitative mass spectrometry to map the glycan and glycoprotein interactors for galectin-3 in live hepatic stellate cells. Understanding the identity of the glycoproteins and defining the structures of the glycans required for galectin-3 mediated hepatic stellate cell activation will empower efforts to design and develop selective therapeutics to mitigate hepatic fibrosis. SignificanceBecause of the weak interactions between individual glycan-binding proteins (GBP), such as galectin-3, and glycans, strategies that allow the direct interrogation of these interactions in living cells remain limited. Thus, the glycan and glycoprotein ligands that are physiologically relevant for galectin-3 binding are insufficiently described. Here, we used a proximity labeling approach that catalytically tags interactors for galectin-3 and identified its pertinent glycan and glycoprotein counter-receptors in live hepatic stellate cells. This study demonstrates that proximity labeling is a powerful tool for mapping GBP complexes in living cells, and when coupled with chemical inhibitors, it can discriminate between protein-protein and protein-glycan interactions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=57 SRC="FIGDIR/small/058586v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@163b731org.highwire.dtl.DTLVardef@19021ddorg.highwire.dtl.DTLVardef@19f53beorg.highwire.dtl.DTLVardef@133009a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2020

G9a methyltransferase governs cell identity in the lung and is required for KRAS G12D tumor development and propagation

Lung development, integrity and repair rely on precise Wnt signaling, which is corrupted in diverse diseases, including cancer. Here, we discover that G9a methyltransferase regulates Wnt signaling in the lung by controlling the transcriptional activity of chromatin-bound {beta}-catenin, through a non-histone substrate. Inhibition of G9a induces transcriptional, morphologic, and molecular changes consistent with alveolar type 2 (AT2) lineage commitment. Mechanistically, G9a activity functions to support regenerative properties of KrasG12D tumors and normal AT2 cells - the predominant cell of origin of this cancer. Consequently, G9a inhibition prevents KrasG12D lung adenocarcinoma tumor formation and propagation,and disrupts normal AT2 cell trans-differentiation. Consistent with these findings, low G9a expression in human lung adenocarcinoma correlates with enhanced AT2 gene expression and improved prognosis. These data reveal G9a as a critical regulator of Wnt signaling, implicating G9a as a potential target in lung cancer and other AT2-mediated lung pathologies.

cancer biology↗