Biology subjects

Tung, C.-H.

Publications and source records attributed to Tung, C.-H..

4 recordsLinked to original sources

bioRxiv2026

Single-Nucleus Profiling Reveals Neuronal Metabolic Collapse During the Transition to Alzheimer's Disease Dementia

Current Alzheimer's disease (AD) neuropathological metrics, including Thal phasing, and Braak staging, often do not accurately predict cognitive status: many cognitively resilient individuals have substantial pathological burdens, whereas some patients with dementia show minimal classical AD pathology. Here, we addressed this discrepancy by investigating the molecular mechanisms underlying AD dementia using single-nucleus RNA-sequencing and single-nucleus multiome datasets. To eliminate cross-modality scaling artifacts and compositional biases inherent in neurodegenerative tissues, we normalized the datasets using our novel framework, bypassing scaling issues of conventional methods that may obscure critical biological signals of interest. We identified neuron-specific suppression of nuclear-encoded mitochondrial genes and their upstream mitochondrial biogenesis signaling (MBS) as primary drivers of clinical dementia. By integrating multi-omic quantitative trait loci, genome-wide association studies, and epigenomic profiles, we delineated genetic and epigenetic changes underlying MBS suppression. This study provides a systematic genomic framework for understanding the mechanisms of cognitive resilience.

bioinformatics↗

bioRxiv2026

Turep: Detecting cross-cancer tumor-reactive T cells in single-cell and spatial transcriptomics data

Tumor-infiltrating lymphocytes are essential for anti-tumor immunity, yet distinguishing tumor-reactive T cells from non-reactive bystander cells remains a significant challenge. Existing signatures, often derived from single cohorts, lack robustness in cross-cancer prediction. We present Turep, a deep learning method designed for robust, cross-cancer prediction of tumor-reactive T cells using single-cell or spatial transcriptomics data. By integrating paired single-cell RNA and T cell receptor sequencing data from seven human malignancies, we identified a pan-cancer tumor-reactive gene signature and leveraged generative data augmentation to address data imbalance. Turep consistently outperformed existing biomarkers, achieving a mean area under the receiver operating characteristic curve of 0.870 across cancer types. In validation across diverse cohorts, we found that Turep-predicted tumor-reactive T cell proportions could predict clinical response to immunotherapy. Furthermore, extending Turep to spatial transcriptomics revealed that tumor-reactive T cells preferentially resided in spatial niches where target cells exhibited elevated antigen presentation. Overall, Turep provides a powerful, generalizable tool for identifying tumor-reactive T cells and their spatial architectures, facilitating personalized cancer immunotherapy strategies.

bioinformatics↗

bioRxiv2024

Extrachromosomal DNA Associates with Nuclear Condensates and Reorganizes Chromatin Structures to Enhance Oncogenic Transcription

Extrachromosomal, circular DNA (ecDNA) is a prevalent oncogenic alteration in cancer genomes, often associated with aggressive tumor behavior and poor patient outcome. While previous studies proposed a chromatin-based mobile enhancer model for ecDNA-driven oncogenesis, its precise mechanism and impact remains unclear across diverse cancer types. Our study, utilizing advanced multi-omics profiling, epigenetic editing, and imaging approaches in three cancer models, reveals that ecDNA hubs are an integrated part of nuclear condensates and exhibit cancer-type specific chromatin connectivity. Epigenetic silencing of the ecDNA-specific regulatory modules or chemically disrupting liquid-liquid phase separation breaks down ecDNA hubs, displaces MED1 co-activator binding, inhibits oncogenic transcription, and promotes cell death. These findings substantiate the trans-activator function of ecDNA and underscore a structural mechanism driving oncogenesis. This refined understanding expands our views of oncogene regulation and opens potential avenues for novel therapeutic strategies in cancer treatment.

genomics↗

bioRxiv2021

RHAMMB-mediated bifunctional nanotherapy targeting Bcl-xL and mitochondria for pancreatic neuroendocrine tumor treatment

The incidence of pancreatic neuroendocrine tumor (PNET) has continued to rise. Due to their indolent feature, PNET patients often present with incurable, metastatic diseases. Novel therapies are urgently needed. We have previously shown that Receptor for Hyaluronic Acid-Mediated Motility isoform B (RHAMMB) and Bcl-xL are upregulated in PNETs and both of them promote PNET metastasis. Because RHAMM protein is undetectable in most adult tissues, we hypothesized that RHAMMB could be a gateway for nanomedicine delivery into PNETs. To test this, we developed RHAMMB-targeting nanoparticle. Inside this nanoparticle, we assembled siRNA against Bcl-xL (siBcl-xL) and mitochondria-fusing peptide KLA. We demonstratsed that RHAMMB-positive PNETs picked up the RHAMMB-targeting nanoparticles. siBcl-xL or KLA alone only killed 30% of PNET cells. In contrast, a synergistic killing effect was achieved with the co-delivery of siBcl-xL and KLA peptide in vitro. Unexpectedly, siBcl-xL induced cell death before reducing Bcl-xL protein levels. The systemically-injected RHAMMB-targeting nanoparticles carrying siBcl-xL and KLA peptide significantly reduced tumor burden in mice bearing RHAMMB-positive PNETs. Together, these findings indicate that the RHAMMB-targeting nanotherapy serves as a promising drug delivery system for PNET and possibly other malignancies upregulating RHAMMB. The combination of siBcl-xL and KLA peptide can be a therapy for PNET treatment.

cancer biology↗