研究成果

Apr, 2022
Jian-Da Lin
Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.
Apr, 2022
Hsueh-Fen Juan
Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cellular context, and stress levels. Accumulating evidence demonstrates that an imbalance in mitochondrial dynamics leads to death in numerous types of human cancer cells. Therefore, modulating mitochondrial dynamics could be a therapeutic target. In this review, we provide an overview of the protein interaction networks involved in mitochondrial dynamics as effective and feasible drug targets and discuss the related potential therapeutic strategies...
Feb, 2022
Hsueh-Fen Juan
Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase six knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotation based on ImmGen database. Composition assessments found that D6KO-derived intestinal leukocytes tend to stay inactivate or immature status. The enrichment analysis showed that D6KO-derived intestinal leukocytes are less sensitive to microbes. The mod PhEA phenotypic analysis showed that the D6KO leukocytes may link to not only immune-associated but also diverse previously non-immune-related diseases. Integrating our dataset with the...
Feb, 2022
Hsueh-Fen Juan
The hourglass model is a popular evo-devo model depicting that the developmental constraints in the middle of a developmental process are higher, and hence the phenotypes are evolutionarily more conserved, than those that occur in early and late ontogeny stages. Although this model has been supported by studies analyzing developmental gene expression data, the evolutionary explanation and molecular mechanism behind this phenomenon are not fully understood yet. To approach this problem, Raff proposed a hypothesis and claimed that higher interconnectivity among elements in an organism during organogenesis resulted in the larger constraints at the mid-developmental stage. By employing stochastic network analysis and gene-set pathway analysis, we aim to demonstrate such changes of...
Nov, 2021
Hsueh-Fen Juan
Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show...
Oct, 2021
Hsueh-Fen Juan and Chien-Yu Chen
The selection of peptides presented by MHC molecules is crucial for antigen discovery. Previously, several predictors have shown impressive performance on binding affinity. However, the decisive MHC residues and their relation to the selection of binding peptides are still unrevealed. Here, we connected HLA alleles with binding motifs via our deep learning-based framework, MHCfovea. MHCfovea expanded the knowledge of MHC-I-binding motifs from 150 to 13,008 alleles. After clustering N-terminal and C-terminal sub-motifs on both observed and unobserved alleles, MHCfovea calculated the hyper-motifs and the corresponding allele signatures on the important positions to disclose the relation between binding motifs and MHC-I sequences. MHCfovea delivered 32 pairs of hyper-motifs and allele...
Oct, 2021
Chun-Hua Hsu
Microbial urate oxidase has emerged as a potential source of therapeutic properties for hyperuricemia in arthritic gout and renal disease. The thermostability and long-term thermal tolerance of the enzyme need to be established to prolong its therapeutic effects. Here, we present the biochemical and structural aspects of a hyperthermostable urate oxidase (TbUox) from the thermophilic microorganism Thermobispora bispora. Enzymatic characterization of TbUox revealed that it was active over a wide range of temperatures, from 30 to 70 °C, with optimal activity at 65 °C and pH 8.0, which suggests its applicability under physiological conditions. Moreover, TbUox exhibits high thermostability from 10 to 65 °C, with Tm of 70.3 °C and near-neutral pH stability from pH 7.0 to 8.0 and high thermal...
Aug, 2021
Chun-Hua Hsu
O-Acetyl-ADP-ribose (OAADPR) is a signaling molecule identified from the conserved sirtuin reaction in Saccharomyces cerevisiae, involved in the important cellular functions of gene silencing, redox regulation, and aging. Here, we performed biochemical and structural characterization of the yeast Poa1p macro domain in detail, uncovering an unusual deacetylase activity favoring 3″- and 1″-isomers of O-acetyl-ADP-ribose. The unique active-site residues of Poa1p contributing to the distinct substrate specificity thus shed light on the divergent branch of a POA1-like subclass. Moreover, disruption of Poa1p expression in yeast showed a striking sensitivity to transcriptional stress, which implies a physiological role in response to nucleotide depletion. These findings provide biochemical and...
Jul, 2021
Hsueh-Fen Juan
LncTx is a network-based method to repurpose drugs that potentially act on lncRNAs in lung cancer. By calculating the proximity between the drug targets and the lncRNA-correlated proteins in the protein-protein interaction (PPI) network, LncTx accurately differentiates anticancer drugs from non-anticancer drugs. Furthermore, the drugs with smaller proximity (proximal drugs) are more effective than the distal drugs. This novel method provides a framework to repurpose old drugs acting on lncRNAs in lung cancer.
May, 2021
Chia-Lang Hsu
Reversal of CD8 T-cell exhaustion was considered a major antitumor mechanism of anti-programmed cell death-1 (PD-1)/ anti-programmed death ligand-1 (PD-L1)-based immune checkpoint inhibitor (ICI) therapy. The aim of this study was to identify markers of T-cell exhaustion that is best associated with ICI treatment efficacy for advanced hepatocellular carcinoma (HCC). Here, we identified a 9-gene signature (LAG3, CD244, CCL5, CXCL9, CXCL13, MSR1, CSF3R, CYBB, and KLRK1) which was functionally associated with CD8 T cell exhaustion. This 9-gene signature had similar predictive values for patients who received single-agent or combination ICI therapy and was not associated with prognosis in HCC patients who received surgery, suggesting that it may outperform other T-cell signatures for...

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