Laboratory Members

1. Epac (RAPGEF3) promotes betaglycan expression to mediate ciprofloxacin-induced suppression of cancer cell migration and metastasis: Mechanistic insights and drug repurposing potential. Biomed Pharmacother. 2025 Aug;189:118261. Liu HP, Tai SB, Jiang JL, Tey SF, Liu PF, Lin MW, Wu SC, Chen YC, Chen CL.
2. Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample. BMC Pulm Med. 2024 Apr 8;24(1):171. Yeh YL, Lai CM, Liu HP.
3. Hospital frailty risk score and outcomes of chronic mesenteric ischemia revascularization: Nationwide Inpatient Sample 2005-2020 analysis. Medicine (Baltimore). 2024 Dec 27;103(52):e41027. Lai CM, Liu HP, Chang WY.
4. Association of Insomnia, Depressive Disorders, and Mood Disorders as Risk Factors With Breast Cancer: A Nationwide. Population-Based Cohort Study of 232,108 Women in Taiwan. Front Oncol. 2021 Oct 11;11:757626. Liu HP, Wei JC, Yip HT, Yeh MH.

In recent years, our team has extensively utilized bioinformatics and machine learning to decode the complexity of the tumor microenvironment (TME) and glycosylation signatures in cancer. We identified the metal transporter SLC39A14 as a critical link between ferroptosis and glycosylation [1]. In pan-cancer analysis (specifically GBM and KIRC), its upregulation correlates with immune suppression (M2 macrophage infiltration) and drug resistance (Cancer Cell Int. 2025;25(1):363). Using machine learning, we identified a 4-gene glycosylation signature (TUB, TCF7L1, MPP2, TMEM59L) in colorectal cancer [2]. High-risk patients exhibited poor survival and increased Treg infiltration, while low-risk groups showed better sensitivity to Trametinib and Oxaliplatin (Int J Mol Sci. 2025;26(4):1648). We demonstrated that long-term exposure to plasticizers (DEHP/MEHP) promotes CRC stemness by downregulating ST8SIA6 [3], altering sialylation patterns, and enhancing Irinotecan resistance (Environ Pollut. 2023;327:121476). We developed a Deep Learning model integrating urine biomarkers (REG1A) and demographics, achieving 91% accuracy in PDAC diagnosis [4], validated by scRNA-seq (Brief Bioinform. 2025;26(6):bbaf583). Immune Evasion: We characterized SLFN5 in colorectal adenocarcinoma (COAD) [5], finding it promotes tumorigenesis via the JAK/STAT/IFN pathway and correlates with Treg infiltration (Int J Med Sci. 2024;21(12):2348-2364).

2. Pharmacology & Toxicology (Drug Repurposing & Mechanism) Pharmacology & Toxicology (Drug Repurposing & Mechanism)

We have a strong track record in elucidating drug mechanisms and mitigating toxicity through repurposing strategies. We discovered that the SGLT2 inhibitor Empagliflozin protects against Sorafenib-induced nephrotoxicity. Mechanistically, it inhibits the COX-2/PGE2 axis and restores GPX4/xCT levels to prevent renal ferroptosis (Toxicol Appl Pharmacol. 2025;504:117512). We reviewed the pharmacological potential of Coronopus didymus [6], confirming its anti-cancer and anti-inflammatory properties supported by flavonoid and glucosinolate content (Phytochem Rev. 2025). We synthesized a membrane-permeable glycolipid derivative, Acetylated Globotetraose (Ac-Gb4), as a targeted therapy for Triple-Negative Breast Cancer (TNBC) [7]. Ac-Gb4 significantly reduced SSEA3/SSEA4 expression and inhibited cancer cell invasion via the FAK/AKT/Caspase-3 signaling axis, demonstrating selective cytotoxicity while sparing normal mammary epithelial cells (Int J Mol Sci. 2024;25(24):13353).

3. Multidisciplinary Approaches (Metabolomics & Public Health) Multidisciplinary Approaches (Metabolomics & Public Health)

Our research energy extends to metabolic regulation and public health assessments. Using 1H-NMR, we revealed that salinity stress induces specific metabolic shifts (beta-alanine, TCA cycle) in Artemia [8], supporting energy production for dormancy (Comp Biochem Physiol Part D Genomics Proteomics. 2025;54:101409). We assessed the psychological impact of COVID-19 on nurses [9], identifying specific risk factors to guide mental health support interventions (Ann Med. 2025;57(1):2447405).

1. Chiang YC, Wang CY, Kumar S, Hsieh CB, Chang KF, Ko CC, et al. Metal ion transporter SLC39A14-mediated ferroptosis and glycosylation modulate the tumor immune microenvironment: pan-cancer multi-omics exploration of therapeutic potential. Cancer Cell Int. 2025;25(1):363.
2. Chuang PK, Chang KF, Chang CH, Chen TY, Wu YJ, Lin HR, et al. Comprehensive Bioinformatics Analysis of Glycosylation-Related Genes and Potential Therapeutic Targets in Colorectal Cancer. Int J Mol Sci. 2025;26(4).
3. Shih PC, Chen HP, Hsu CC, Lin CH, Ko CY, Hsueh CW, et al. Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations. Environ Pollut. 2023;327:121476.
4. Solomon DD, Ko CC, Chen HY, Kumar S, Wulandari FS, Xuan DTM, et al. A machine learning framework using urinary biomarkers for pancreatic ductal adenocarcinoma prediction with post hoc validation via single-cell transcriptomics. Brief Bioinform. 2025;26(6).
5. Wu YJ, Chiao CC, Chuang PK, Hsieh CB, Ko CY, Ko CC, et al. Comprehensive analysis of bulk and single-cell RNA sequencing data reveals Schlafen-5 (SLFN5) as a novel prognosis and immunity. Int J Med Sci. 2024;21(12):2348-64.
6. Ali W, Sehar M, Nayab D-e, Saeed R, Lee Y-K, Chuang P-K. A comprehensive review of the phytochemical and pharmacological attributes of Coronopus didymus. Phytochemistry Reviews. 2025.
7. Lee YK, Sehar M, Botcha L, Chuang PK. Acetylated Globotetraose (Ac-Gb4) Suppresses Triple-Negative Breast Cancer Through FAK/AKT Signaling Pathway. Int J Mol Sci. 2024;25(24).
8. Lee WY, Liu CH, Yu BH, Lee YK, Kuo CH, Huang CY, et al. (1)H NMR-based metabolomic analysis of hypersalinity-induced oviparity in brine shrimp. Comp Biochem Physiol Part D Genomics Proteomics. 2025;54:101409.
9. Lin HR, Lee YK, Chang CL, Kuo CH, Ho HY, Wu CJ, et al. Assessment of psychological health effects of nurses during 2022-2023 of the COVID-19 pandemic: a descriptive study in Southern Taiwan. Ann Med. 2025;57(1):2447405.

1. Ke TY, Wang SW, Lin ZY, Ganesan G, Lai CT, Yen JY, Chu TH, Lin YC, Cheng YB. (2025, Nov). Polyketide Derivatives from the Macroalga-Associated Fungus Penicillium sclerotiorum Exhibiting Anti-Lymphangiogenic Effect. Journal of Natural Products.
2. Kung ML, Chu TH, Hsieh S, Li CC, Li WM, Yeh BW, Wu WJ. (2025, Nov). Phenolic zingerone nanoparticles impede cell cycle progression to compete against human urothelial carcinoma. Biomed Pharmacother ., 192:118675.
3. Tsai MK, Lee WC, Huang SC, Huang CC, Wang YC, Yuan CH, Wang CC, Liu CH, Huang NC, Chang YC, Fang CC, Yeh BW, Yang JH, Ho YC, Lee YK, Wu CC, Hsiao KY, Liu WL, Yang SM, Huang CY#, Chu TH#.(#corresponding authors) (2025, Nov). Empagliflozin attenuates sorafenib-promoted renal ferroptosis and inflammation by targeting cyclooxygenase-2/prostaglandin E2 axis. Toxicol Appl Pharmacol , 504:117512.
4. Wu YC, Lin YP, Chang CY, Cheng HY, Chu TH, Chen CC, Kuo SM (2025, Aug). Enhanced Hair Growth Through Transdermal Delivery of Bacopa Monnieri Extract Using a Needle-Free Supersonic Atomizer. Journal of Medical and Biological Engineering, 45, 573-590.
5. Lee MT, Peng WH, Hsu TW, Chu TH, Teng YN, Wu CC, Lee YK, Lan YY, Ho YC (2025, Jul). Boosting the ventrolateral periaqueductal gray-ventral tegmental area pathway by disinhibition of group II mGluRs alleviates chronic restraint stress-induced depression-like behavior in mice. J Psychopharmacol, 2698811251351611.
6. Yang SM, Hu TH, Ching-Wu J, Yi LN, Kuo HM, Kung ML, Chu TH, Huang ST, Huang CC, Lin YW, Tai MH (2025, Mar). Hepatoma-derived growth factor promotes liver carcinogenesis by inducing phosphatase and tensin homolog inactivation. Lab Invest , 104127.
7. Wu CC, Lee YK, Tsai JK, Su YT, Ho YC, Chu TH, Chen KT, Chang CL, Chen JS (2024, Dec). Cholinesterase Inhibitor Reveals Synergistic Potential for Neural Stem Cell-Based Therapy in the 5xFAD Mouse.
8. Liu CH, Ho YC, Lee WC, Huang CY, Lee YK, Hsieh CB, Huang NC, Wu CC, Nguyen NUN, Hsu CC, Chen CH, Chen YC, Huang WC, Lu YY, Fang CC, Chang YC, Chang CL, Tsai MK, Wen ZH, Li CZ, Li CC, Chuang PK, Yang SM, Chu TH#, Huang SC#. (#corresponding authors) (2024, Nov). Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity. Environ Toxicol, 39(11):4844-4858.
9. Cheng MY, Hsu IC, Huang SY, Chuang YT, Ke TY, Chang HW, Chu TH, Chen CY, Cheng YB (2024, May). Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp. Mar Drugs , 22(5):219.
10. Hu TH, Wu JC, Huang ST, Chu TH, Han AJ, Shih TW, Chang YC, Yang SM, Ko CY, Lin YW, Kung ML, Tai MH. (2023, Nov). HDGF stimulates liver tumorigenesis by enhancing reactive oxygen species generation in mitochondria. Journal of Biological Chemistry, 299(11): 105335.
11. Wang HK, Su YT, Ho YC, Lee YK, Chu TH, Chen KT, Wu CC. (2023, Sep). HDAC1 is Involved in Neuroinflammation and Blood-Brain Barrier Damage in Stroke Pathogenesis. Journal of inflammation research, 16: 4103–4116.
12. Chen TY, Hsu CW, Chang YP, Wang MT, Wu YJ, Wang CH, Wang KY, Chu TH#, Lee YK#. (#corresponding authors) (2023, Jul). Percutaneous transhepatic duodenal drainage is good option for afferent loop syndrome for obstructive colorectal cancer patient with history of Billroth’s operation II: A case report of a rare postoperative complication. Clinical case report., 11(7):e7725.
13. Huang SC*, Huang CC*, Ko CY, Huang CY, Liu CH, Lee YK, Chen TY, Hsueh CW, Tzou SJ, Tai MH, Hu TH, Tsai MC, Lee WC, Ho YC, Wu CC, Chang YC, Chang JJ, Liu KH, Li CC, Wen ZH, Chang CL#, Chu TH# (#corresponding authors) (2023, Mar). Slow Skeletal Muscle Troponin T Acts as a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma. GENE, 147331.
14. Kung ML, Huang ST, Tsai KW, Chu TH, Hsieh S (2023, Feb). Nanosized zingerone-triggered anti-angiogenesis contributes to tumor suppression in human hepatocellular carcinoma. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 658:130697.
15. Weng SW, Wu JC, Shen FC, Chang YH, Su YJ, Lian WS, Tai MH, Su CH, Chuang JH, Lin TK, Liou CW, Chu TH, Kao YH, Wang FS, Wang PW (2023, Jan). Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation. DIABETOLOGIA.
16. Chu TH*, Ko CY*, Tai PH, Chang YC, Huang CC, Wu TY, Chan HH, Wu PH, Weng CH, Lin YW, Kung ML, Fang CC, Wu JC, Wen ZH, Lee YK, Hu TH, Tai MH (*first authors) (2022, Oct). Leukocyte cell-derived chemotaxin 2 regulates epithelial-mesenchymal transition and cancer stemness in hepatocellular carcinoma. JOURNAL OF BIOLOGICAL CHEMISTRY, 298(10), 102442.
17. Kan HW, Peng WH, Wu CC, Wang DW, Lee MT, Lee YK, Chu TH, Ho YC (2022, Oct). Rapid antidepressant-like effects of muscarinic receptor antagonists require BDNF-dependent signaling in the ventrolateral periaqueductal gray. Psychopharmacology (Berl).
18. Lee MG*, Lee YK*, Huang SC, Chang CL, Ko CY, Lee WC, Chen TY, Tzou SJ, Huang CY, Tai MH, Lin YW, Kung ML, Tsai MC, Chen YL, Chang YC, Wen ZH, Huang CC#, Chu TH# (#corresponding authors) (2022, Apr). DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis. Genes, 13(4), 629.
19. Lee WC, Chiu CH, Chu TH, Chien YS (2022, Apr). WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease. Frontiers in Cell and Developmental Biology, 10:876723.
20. Ko CY*, Chu TH*, Hsu CC, Chen HP, Huang SC, Chang CL, Tzou SJ, Chen TY, Lin CC, Shih PC, Lin CH, Chang CF, Lee YK (*first authors) (2022, Mar). Bioinformatics Analyses Identify the Therapeutic Potential of ST8SIA6 for Colon Cancer. Journal of Personalized Medicine, 4;12(3):401.
21. Yang CM, Chu TH, Tsai KW, Hsieh S, Kung ML (2022, Jan). Phytochemically Derived Zingerone Nanoparticles Inhibit Cell Proliferation, Invasion and Metastasis in Human Oral Squamous Cell Carcinoma. Biomedicines, 29;10(2):320.