1. 楊舒渝, 李貞穎, 辜韋智, 張凱明, and 李孟真^*. (2026) 探討中藥徐長卿之有效成分丹皮酚對於乳癌細胞株之影響. 中醫藥研究論叢 29(1): 15-35.

2. Chen YL, Lin WN, Pan PY, Ku WC, Wang P, Yip PK, Tsui KC, Wu YN^*, and Lin YH^*. (2026) Generation of a novel dysferlin microdeletion knock-in mouse model mimicking muscular dystrophy-like pathology. Sci Rep 16(1): 15322. PMID: 41922468.

3. Chen SK, Wang YC, Hsieh YH, Huang CJ, and Ku WC^* (2026). Timescale-dependent phosphoproteomic remodeling and motility-associated adaptation under chronic cabozantinib exposure in renal cell carcinoma. Cancer Genom Proteom 23(2): 265-280. PMID: 41771580.

4. Lee YC, Ku WC, Hung YL, Chen YC, Hung CF, Wang JT, and Liu WL^*. (2025) Factors associated with beyond-therapeutic serum voriconazole trough level among critically ill patients with invasive fungal infections. BMC Infect Dis 25(1): 1807. PMID: 41275081.

5. Ku WC, Phan NN, Liu CY, Huang CJ, Liao CC, Huang YC, Kong PH, Tseng LM^*, and Huang CC^*. (2025) Collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes by functional proteomics from core needle biopsy samples of Taiwanese breast cancer. Biophys Rep 44: 102210. PMID: 40927672.

6. Ku WC, Liu CY, Huang CJ, Liao CC, Huang YC, Kong PH, Hsieh CC, H, Tseng LM^*, and Huang CC^*. (2025) Integrating functional proteomics and next generation sequencing reveals potential therapeutic targets for Taiwanese breast cancer. Clin Proteomics 22(1): 4. PMID: 39844043.

7. Pan PY, Ke CC, Wang YY, Lin YH, Ku WC, Au CF, Chan CC, Huang CY, and Lin YH^*. (2024) Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects, Dev Dyn 253(11): 1024-1035. PMID: 38822685.

8. Wang, YY, Lin, YH, Wu, VC, Lin, YH, Huang, CY, Ku, WC, and Sun, CY^*. (2023) Decreased Klotho expression causes accelerated decline of male fecundity through oxidative injury in murine testis. Antioxidants (Basel) 12(9). PMID: 37759974.

9. Chen YN, Shih, CY, Guo, SL, Liu, CY, Shen MH, Chang SC, Ku WC, Huang CC^*, and Huang CJ^*. (2023) Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens. Biomed Rep 18(3): 22. PMID: 36846616.

10. Lu ML, Ku WC, Syifa N, Hu SC, Chou CT, Wu YH, Kuo PH, Chen CH, Chen WJ, and Wu TH^*. (2022) Developing a sensitive platform to measure 5-methyltetrahydrofolate in subjects with MTHFR and PON1 gene polymorphisms. Nutrients 14(16): 3320. PMID: 36014826.

11. Huang A, Huang SY, Shah P, Ku WC, Huang KT, Liu YF, Su CL, and Huang RS^*. (2022) Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics signatures to mediate human breast cancer malignancy. J Nutr Biochem 106109000. PMID: 35460832.

12. Hsu WH, Han DS, Ku WC, Chao YM, Chen CC^*, and Lin YL^*. (2022) Metabolomic and proteomic characterization of sng and pain phenotypes in fibromyalgia. Eur J Pain 26(2): 445-462. PMID: 34608709.

13. Cheng YC, Huang CJ, Ku WC, Guo SL, Tien LT, Lee YJ^*, and Chien, CC^*. (2022) Downregulated calcium-binding protein S100A16 and HSP27 in placenta-derived multipotent cells induce functional astrocyte differentiation. Stem Cell Rev Rep, 18(2): 839-852. PMID: 35061207.

14. Chang CC, Kao WY, Liu CY, Su HH, Kan YA, Lin PY, Ku WC, Chang KW, Yang RN, and Huang CJ^*. (2022) Butyrate supplementation regulates expression of chromosome segregation 1like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer. Int J Oncol 60(6), 64. PMID: 35417036.

15. Wang YC, Ku WC, Liu, CY, Cheng, YC, Chien, CC, Chang, KW, and Huang, CJ^*. (2021) Supplementation of probiotic Butyricicoccus pullicaecorum mediates anticancer effect on bladder urothelial cells by regulating butyrate-responsive molecular signatures. Diagnostics 11(12): 2270. PMID: 34943506.

16. Liu CY, Huang CS, Huang CC, Ku WC, Shih HY, and Huang CJ^*. (2021) Co-occurrence of differentiated thyroid cancer and second primary malignancy: Correlation with expression profiles of mismatch repair protein and cell cycle regulators. Cancers (Basel) 13(21): 5486. PMID: 34771648.

17. Chen RL, Fang LH, Yang XY, El Amrani M, Uijtendaal EV, Chen YF, and Ku WC^*. (2021) Therapeutic drug monitoring of busulfan in patients undergoing hematopoietic cell transplantation: A pilot single-center study in Taiwan. Pharmaceuticals 14(7): 613. PMID: 34206798.

18. Chen SK, Wang YC, Lin TY, Wu HJ, Huang CJ, and Ku WC^*. (2021) G-Protein-coupled estrogen receptor 1 agonist G-1 perturbs sunitinib resistance-related phosphoproteomic signatures in renal cell carcinoma. Cancer Genom Proteom 18(3): 207-220. PMID: 33893075.

19. Ku WC, Sridharan B, Chen JY, Li JY, Yang SY, and Lee MJ^*. (2021) Kaempferitrin-treated HepG2 differentially expressed exosomal markers and affect extracellular vesicle sizes in the secretome. Biomolecules 11(2): 187. PMID: 33572893.

20. Wang YY, Ke CC, Chen YL, Lin YH, Yu IS, Ku WC, O'Bryan MK, and Lin YH^*. (2020) Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice. PLoS Genet 16(9): e1009020. PMID: 32976492.

21. Lin YH, Huang CY, Ke CC, Wang YY, Lai TH, Liu HC, Ku WC, Chan CC, and Lin YH^*. (2020) ACTN4 mediates SEPT14 mutation-induced sperm head defects. Biomedicines 8(11): 518. PMID: 33228246.

22. Cheng YC, Ku WC, Tseng TT, Wu CP, Li MJ, and Lee SC^*. (2020) Anchorage independence altered vasculogenic phenotype of melanoma cells through downregulation in aminopeptidase N /syndecan-1/integrin beta4 axis. Aging (Albany NY) 12(17): 16803-16819. PMID: 32756007.

23. Huang KT, Shen YL, Lee CN, Chu KY, Ku WC, Liu CY, and Huang RS^*. (2020) Using differential threshold effects of individual and combined periconceptional methyl donor status on maternal genomic LINE-1 and imprinted H19 DNA methylation to predict birth weight variance in the Taiwan Pregnancy-Newborn Epigenetics (TPNE) cohort study. J Nutr 150(1): 108-117. PMID: 31504733.

24. Yeh TT, Ho MY, Chen WY, Hsu YC, Ku WC, Tseng HW, Chen ST, and Chen SF^*. (2019) Comparison of different fractionation strategies for in-depth phosphoproteomics by liquid chromatography tandem mass spectrometry. Anal Bioanal Chem 411(15): 3417-3424. PMID: 31011783.

25. Ku WC, Chen SK, Lin CM, Tang C, and Wang YC^*. (2019) Label-free quantitative phosphoproteomics reveals the role of beta-estradiol in sunitinib-resistant renal cell carcinoma growth via perturbing transforming growing factor-beta pathway. Urol Sci 30(3): 107-113.

26. Hsu WH, Lee CH, Chao YM, Kuo CH, Ku WC, Chen CC^*, and Lin YL^*. (2019) ASIC3-dependent metabolomics profiling of serum and urine in a mouse model of fibromyalgia. Sci Rep 9(1): 12123. PMID: 31431652.

27. Hsu WH, Shen YC, Shiao YJ, Kuo CH, Lu CK, Lin TY, Ku WC^*, and Lin YL^*. (2019) Combined proteomic and metabolomic analyses of cerebrospinal fluid from mice with ischemic stroke reveals the effects of a Buyang Huanwu decoction in neurodegenerative disease. PLoS One 14(1): e0209184. PMID: 30645580.

28. Ke CC, Lin YH, Wang YY, Wu YY, Chen MF, Ku WC, Chiang HS, and Lai TH^*. (2018) TBC1D21 potentially interacts with and regulates Rap1 during murine spermatogenesis. Int J Mol Sci 19(11): 3292. PMID: 30360518.

29. Ku WC, Chang YL, Wu SF, Shih HN, Tzeng YM, Kuo HR, Chang KM, Agrawal DC, Liu BL, Chang CA, Huang S, and Lee MJ^*. (2017) A comparative proteomic study of secretomes in kaempferitrin-treated CTX TNA2 astrocytic cells. Phytomedicine 36: 137-144. PMID: 29157807.

30. Tsai CF, Ku WC, Chen YJ, and Ishihama Y^*. (2017) Absolute phosphorylation stoichiometry analysis by motif-targeting quantitative mass spectrometry. Methods Mol Biol 1636: 313-325. PMID: 28730488.

31. Huang JH, Ku WC, Chen YC, Chang YL, and Chu CY^*. (2017) Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6. Sci Rep 7: 42853. PMID: 28216671.

32. Lin YH, Ke CC, Wang YY, Chen MF, Chen TM, Ku WC, Chiang HS, and Yeh CH^*. (2017) RAB10 interacts with the male germ cell-specific GTPase-activating protein during mammalian spermiogenesis. Int J Mol Sci 18(1): 97. PMID: 28067790.

33. Wu ST, Ku WC, Huang CJ, Wang YJ, Lin CM, and Chen SK^*. (2016) Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells. J Biomed Sci 23(1): 67. PMID: 27680214.

34. Hirata H, Ku WC, Yip AK, Ursekar CP, Kawauchi K, Roy A, Guo AK, Vedula SR, Harada I, Chiam KH, Ishihama Y, Lim CT, Sawada Y^*, and Sokabe M^*. (2016) MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility. J Cell Sci 129(19): 3574-3582. PMID: 27528401.

35. Cheng YC, Huang CJ, Lee YJ, Tien LT, Ku WC, Chien R, Lee FK^*, and Chien CC^*. (2016) Knocking down of heat-shock protein 27 directs differentiation of functional glutamatergic neurons from placenta-derived multipotent cells. Sci Rep 6: 30314. PMID: 27444754.

36. Chen KC, Lin CM, Huang CJ, Chen SK, Wu ST, Chiang HS^*, and Ku WC^*. (2016) Dual Roles of 17-beta estradiol in estrogen receptor-dependent growth inhibition in renal cell carcinoma. Cancer Genom Proteom 13(3): 219-230. PMID: 27107064.

37. Hu CW, Hsu CL, Wang YC, Ishihama Y, Ku WC, Huang HC^*, and Juan HF^*. (2015) Temporal phosphoproteome dynamics induced by an ATP synthase inhibitor citreoviridin. Mol Cell Proteomics 14(12): 3284-3298. PMID: 26503892.

38. Tsai CF, Wang YT, Yen HY, Tsou CC, Ku WC, Lin PY, Chen HY, Nesvizhskii AI, Ishihama Y^*, and Chen YJ^*. (2015) Large-scale determination of absolute phosphorylation stoichiometries in human cells by motif-targeting quantitative proteomics. Nat Commun 6: 6622. PMID: 25814448.

39. Hu CW, Tseng CW, Chien CW, Huang HC, Ku WC, Lee SJ^*, Chen YJ^*, and Juan HF^*. (2013) Quantitative proteomics reveals diverse roles of miR-148a from gastric cancer progression to neurological development. J Proteome Res 12(9): 3993-4004. PMID: 23869555.

40. Araki Y, Ku WC, Akioka M, May AI, Hayashi Y, Arisaka F, Ishihama Y, and Ohsumi Y^*. (2013) Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity. J Cell Biol 203(2): 299-313. PMID: 24165940.

41. Ku WC, and Ishihama Y^*. (2013) Proteomic analyses of post-translational modifications. In: Li, S. Y. F., ed. Quantitative Proteome Analysis, pp. 45-66, Pan Stanford Publishing.

42. Hu CW, Lin MH, Huang HC, Ku WC, Yi TH, Tsai CF, Chen YJ, Sugiyama N, Ishihama Y^*, Juan HF^*, and Wu SH^*. (2012) Phosphoproteomic analysis of Rhodopseudomonas palustris reveals the role of pyruvate phosphate dikinase phosphorylation in lipid production. J Proteome Res 11(11): 5362-5375. PMID: 23030682.

43. Ku WC, Sugiyama N, and Ishihama Y^*. (2012) Large-scale protein phosphorylation analysis by mass spectrometry-based phosphoproteomics. In: Mukai, H., ed. Protein Kinase Technologies, pp. 35-46, Humana Press.

44. Chen YJ, Ku WC, Lin PY, Chou HC, Khoo KH, and Chen YJ^*. (2010) S-Alkylating labeling strategy for site-specific identification of the S-nitrosoproteome. J Proteome Res 9(12): 6417-6439. PMID: 20925432.

45. Ku WC, Chiu SK, Chen YJ, Huang HH, Wu WG, and Chen YJ^*. (2009) Complementary quantitative proteomics reveals that transcription factor AP-4 mediates E-box-dependent complex formation for transcriptional repression of HDM2. Mol Cell Proteomics 8(9): 2034-2050. PMID: 19505873.

46. Chen YJ, Ku WC, Feng LT, Tsai ML, Hsieh CH, Hsu WH, Liaw WF, Hung CH^*, and Chen YJ^*. (2008) Nitric oxide physiological responses and delivery mechanisms probed by water-soluble Roussin’s red ester and {Fe(NO)₂}¹⁰ DNIC. J Am Chem Soc 130(33): 10929-10938. PMID: 18661983.

47. Chen CC, Ku WC, Chiu SK, and Tzeng CM^*. (2006) Deoxyribonucleic acid hybridization acceleration by photovoltaic effect. Appl Phys Lett 89(23), 233902.

48. Ku WC, Lau WK, Tseng YT, Tzeng CM, and Chiu SK^*. (2004) Dextran sulfate provides a quantitative and quick microarray hybridization reaction. Biochem Biophys Res Commun 315(1): 30-37. PMID: 15013421.

49. Chu SK, Hsu M, Ku WC, Tu CY, Tseng YT, Lau WK, Yan RY, Ma JT, and Tzeng CM^*. (2003) Synergistic effects of epoxy- and amine-silanes on microarray DNA immobilization and hybridization. Biochem J 374(Pt 3): 625-632. PMID: 12809552.

50. Ku WC, Cheng AJ, and Wang TC^*. (1997) Inhibition of telomerase activity by PKC inhibitors in human nasopharyngeal cancer cells in culture. Biochem Biophys Res Commun 241(3): 730-736. PMID: 9434777.

Our research applies mass spectrometry-based functional proteomics to investigate disease-associated signaling networks, identify therapeutic targets, and advance precision medicine. By integrating quantitative proteomics, phosphoproteomics, targeted mass spectrometry, and computational analysis, we characterize dynamic molecular pathways that drive disease progression and therapeutic response. Our work bridges analytical chemistry with translational biomedical research to transform large-scale proteomic data into mechanistic insights and clinically actionable discoveries. Current research focuses on three major areas.

Precision Oncology through Functional Proteomics
Our primary research focuses on applying quantitative proteomics and phosphoproteomics to decipher functional signaling networks underlying cancer progression and therapeutic resistance. Renal cell carcinoma (RCC) serves as our principal disease model because of its extensive molecular heterogeneity and the frequent development of resistance to tyrosine kinase inhibitors (TKIs). Using next-generation data-independent acquisition (DIA)-based phosphoproteomics and multiplex quantitative proteomics, our laboratory systematically characterizes kinase signaling dynamics, identifies phosphoproteomic signatures associated with TKI resistance, and uncovers therapeutically actionable signaling pathways. Current studies investigate phosphoproteomic remodeling during acquired drug resistance, the regulatory role of CDK18 in RCC proliferation and cell adhesion, and the molecular mechanisms by which probiotic-derived short-chain fatty acids suppress RCC growth. Building upon our previous findings that activation of G-protein-coupled estrogen receptor 1 (GPER1) attenuates sunitinib resistance, our ongoing research further employs deep DIA phosphoproteomics to guide the repurposing of selective estrogen receptor modulators (SERMs) for treating TKI-resistant RCC. Beyond RCC, we integrate functional proteomics with genomic profiling to characterize molecular heterogeneity across cancer subtypes. Current projects investigate subtype-specific proteomic signatures and extracellular matrix remodeling in breast cancer, while collaborative studies explore proteomic biomarkers and disease mechanisms in colorectal cancer and other malignancies. These efforts aim to facilitate biomarker discovery, patient stratification, and mechanism-based therapeutic development for precision oncology.

Clinical Mass Spectrometry and Therapeutic Drug Monitoring
Our laboratory develops highly sensitive and robust LC–MS-based analytical platforms for clinical chemistry and therapeutic drug monitoring (TDM). We have established multiplex quantitative assays for antifungal agents and busulfan to support individualized pharmacotherapy in hematopoietic stem cell transplantation. Current research extends targeted LC–MS methodologies to biologic therapeutics, particularly monoclonal antibodies used in autoimmune diseases, by accurately quantifying pharmacologically active drug species with superior analytical specificity and precision. We also develop targeted MS assays for endogenous metabolites and disease-associated biomarkers to support precision medicine and translational clinical research. These efforts aim to provide clinically applicable analytical platforms that complement or surpass conventional immunochemical methods.

Proteomics in Human Disease and Translational Biology
Beyond oncology, our laboratory applies advanced proteomic technologies to investigate diverse human diseases. Ongoing collaborative projects include elucidating the dual roles of autophagy and extracellular vesicles in male reproduction, investigating the molecular pathology of ossification of the posterior longitudinal ligament, characterizing mitochondrial responses to electrical stimulation in retinal ganglion cells, and exploring exosome-mediated signaling associated with colorectal cancer progression. By integrating quantitative proteomics, phosphoproteomics, metabolomics, proximity labeling, and cellular and animal models, these studies seek to uncover disease mechanisms, identify novel biomarkers, and discover potential therapeutic targets.