研究方向

Methodologies play a crucial role in driving scientific advancement. Mass spectrometric techniques have been integrated into our skill set for protein structure analysis.  My laboratory has pioneered novel analytical methods based on the elution properties of peptide products from protein digestion, uncovering cellular protein modifications such as phosphorylation and acetylation for many groups worldwide.  My subsequent experience in the biotechnology industry further inspired us to develop innovative methods that enable the simultaneous screening of multiple types of protein modifications in a single analysis.

Around a decade ago, this challenge led us to explore the potential of protein complexes as long-sought disease biomarkers.  With our in-depth knowledge about plasma protein structures, we developed platform technologies to profile proteins present in liquid chromatography fractions from the tested plasma sample.  These efforts have proven to be a robust approach, quickly yielding several complex biomarkers for various cancers.  Furthermore, these protein structural alterations can be quantitatively assessed using automated western blotting analyses, shaping the future direction for developing clinical diagnostic tests aimed at high-sensitivity screening for diseases, such as early-stage cancers.

Research Interest

Biomarker discovery, drug discovery, proteomics/cell biology/protein chemistry, medicine, mass spectrometry, VBA programming, philosophy

研究著作

Chen DH, Chang YW, Chien CH, Torng PL and Tsay YG. (2024) Redefined complement C3c structures had significant increase in the plasma of epithelial ovarian cancer patients.  In Press

Fann YN, Teo WH, Lee HC, Liao CC, Tsay YG, Huang TF, Lo JF. (2024) Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism. J Cachexia Sarcopenia Muscle. Epub ahead of print.

Kuo CW, Chen DH, Tsai MT, Lin CC, Cheng HW, Tsay YG, Wang HT. (2023) Pyruvate kinase M2 modification by a lipid peroxidation byproduct acrolein contributes to kidney fibrosis. Front Med (Lausanne). 10:1151359.

Lin KY, Tsay YG, Chang CA. (2022) Effects of polyallylamine-coated nanoparticles on the optical and photochemical properties of rose bengal. J Chin Med Assoc. 85(9):901-908.

Chiou WC, Hsu MS, Chen YT, Yang JM, Tsay YG, Huang HC, Huang C. (2021) Repurposing existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors. J Enzyme Inhib Med Chem. 36(1):147-153.

Liu M, Sui D, Dexheimer T, Hovde S, Deng X, Wang KW, Lin HL, Chien HT, Kweon HK, Kuo NS, Ayoub CA, Jimenez-Harrison D, Andrews PC, Kwok R, Bochar DA, Kuret J, Fortin J, Tsay YG, Kuo MH. (2020) Hyperphosphorylation renders Tau prone to aggregate and to cause cell death. Mol Neurobiol. 57(11):4704-4719.

Jeng KS, Jeng CJ, Jeng WJ, Sheen IS, Li SY, Leu CM, Tsay YG, Chang CF. (2019) Sonic Hedgehog signaling pathway as a potential target to inhibit the progression of hepatocellular carcinoma. Oncol Lett. 18(5):4377-4384.

Lo CH, Lin IH, Yang TT, Huang YC, Tanos BE, Chou PC, Chang CW, Tsay YG, Liao JC, Wang WJ. (2019) Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation. J Cell Biol. 218(10):3489-3505

Chen YS, Chang CW, Tsay YG, Huang LY, Wu YC, Cheng LH, Yang CC, Wu CH, Teo WH, Hung KF, Huang CY, Lee TC, Lo JF. (2018) HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling. Theranostics. 8(14):3841-3855.

Chang CW, Chen YS, Tsay YG, Han CL, Chen YJ, Yang CC, Hung KF, Lin CH, Huang TY, Kao SY, Lee TC, Lo JF. (2018) ROS-independent ER stress-mediated NRF2 activation promotes warburg effect to maintain stemness-associated properties of cancer-initiating cells. Cell Death Dis. 9(2):194.

Chiu HY, Tsay YG, Hung SC. (2017) Involvement of mTOR-autophagy in the selection of primitive mesenchymal stem cells in chitosan film 3-dimensional culture. Sci Rep. 7(1):10113.

Li LH, How CK, Kao WF, Chiu YH, Meng C, Hsu CC, Tsay YG. (2017) The impact of hepatitis B carrier on cardiac troponin I in 100-km ultramarathon runners. J Chin Med Assoc. 80(6):347-352.

Yu YT, Chien SC, Chen IY, Lai CT, Tsay YG, Chang SC, Chang MF. (2016) Surface vimentin is critical for the cell entry of SARS-CoV. J Biomed Sci. 23:14.

Li JJ, Lan KL, Chang SF, Chen YF, Tsai WC, Chiang PH, Lin MH, Fischer WB, Shih YS, Yen SH, Liu RS, Tsay YG, Wang HE, Chang CA. (2015) Development and characterization of the recombinant human VEGF-EGF dual-targeting fusion protein as a drug delivery system. Bioconjug Chem. 26(12):2481-96.

Liu NY, Lee HH, Chang ZF, Tsay YG. (2015) Examination of segmental average massspectra from liquid chromatography-tandem mass spectrometric (LC-MS/MS) data enables screening of multiple types of protein modifications. Anal Chim Acta. 892:115-22.

Huang CY, Chen WM, Tsay YG, Hsieh SC, Lin Y, Lee WJ, Sheu WH, Chiang AN. (2015) Differential regulation of protein expression in response to polyunsaturated fatty acids in the liver of apoE-knockout mice and in HepG2 cells. J Biomed Sci. 22:12.

Weng RR, Shu HW, Chin SW, Kao Y, Chen TW, Liao CC, Tsay YG, Ng WV. (2014) OMICS in ecology: systems level analyses of Halobacterium salinarum reveal large-scale temperature-mediated changes and a requirement of CctA for thermotolerance. OMICS. 18(1):65-80.

Weng RR, Chu LJ, Shu HW, Wu TH, Chen MC, Chang Y, Tsai YS, Wilson MC, Tsay YG, Goodlett DR, Ng WV. (2013) Large precursor tolerance database search – a simple approach for estimation of the amount of spectra with precursor mass shifts in proteomic data. J Proteomics. 91:375-84.

Chen YF, Chang CA, Lin YH, Tsay YG. (2013) Determination of accurate protein monoisotopic mass with the most abundant mass measurable using high-resolution mass spectrometry. Anal Biochem. 1;440(1):108-13.

Huang C, Jiang JY, Chang SC, Tsay YG, Chen MR, Chang MF. (2013) Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen. J Virol. 87(3):1596-604.

Chang CA, Wang IF, Lee HY, Meng CN, Liu KY, Chen YF, Yang TH, Wang YM, Tsay YG. (2012) The formation stability, hydrolytic behavior, mass spectrometry, DFT study, and luminescence properties of trivalent lanthanide complexes of H2ODO2A. Dalton Trans. 41(48):14697-706

Chang YH, Lee SH, Chang HC, Tseng YL, Lai WW, Liao CC, Tsay YG, Liao PC. (2012) Comparative secretome analyses using a hollow fiber culture system with label-free quantitative proteomics indicates the influence of PARK7 on cell proliferation and migration/invasion in lung adenocarcinoma. J Proteome Res. 11(11):5167-85.

Huang YL, Chung TW, Chang CM, Chen CH, Liao CC, Tsay YG, Shaw GC, Liaw SH, Sun CM, Lin CH. (2012) Qualitative analysis of the fluorophosphonate-based chemical probes using the serine hydrolases from mouse liver and poly-3-hydroxybutyrate depolymerase (PhaZ) from Bacillus thuringiensis. Anal Bioanal Chem. 404(8):2387-96.

Lai JH, She TF, Juang YM, Tsay YG, Huang AH, Yu SL, Chen JJ, Lai CC. (2012) Comparative proteomic profiling of human lung adenocarcinoma cells (CL 1-0) expressing miR-372. Electrophoresis. 33(4):675-88.

Chuang HH, Yang CH, Tsay YG, Hsu CY, Tseng LM, Chang ZF, Lee HH. (2012) ROCKII Ser1366 phosphorylation reflects the activation status. Biochem J. 443(1):145-51.

Shih YY, Nakagawara A, Lee H, Juan HF, Jeng YM, Lin DT, Yang YL, Tsay YG, Huang MC, Pan CY, Hsu WM, Liao YF. (2012) Calreticulin mediates nerve growth factor-induced neuronal differentiation. J Mol Neurosci. 47(3):571-81.

Shih YY, Lee H, Nakagawara A, Juan HF, Jeng YM, Tsay YG, Lin DT, Hsieh FJ, Pan CY, Hsu WM, Liao YF. (2011) Nuclear GRP75 binds retinoic acid receptors to promote neuronal differentiation of neuroblastoma. PLoS One. 6(10):e26236.

Liao KA, Tsay YG, Huang LC, Huang HY, Li CF, Wu TF. (2011) Search for the tumor-associated proteins of oral squamous cell carcinoma collected in Taiwan using proteomics strategy. J Proteome Res. 10(5):2347-58.

Wu MJ, Jan CI, Tsay YG, Yu YH, Huang CY, Lin SC, Liu CJ, Chen YS, Lo JF, Yu CC. (2010) Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol Cancer. 9:283.

Chang HH, Lee H, Hu MK, Tsao PN, Juan HF, Huang MC, Shih YY, Wang BJ, Jeng YM, Chang CL, Huang SF, Tsay YG, Hsieh FJ, Lin KH, Hsu WM, Liao YF. (2010) Notch1 expression predicts an unfavorable prognosis and serves as a therapeutic target of patients with neuroblastoma. Clin Cancer Res. 16(17):4411-20.

Wu HY, Tseng VS, Chen LC, Chang HY, Chuang IC, Tsay YG, Liao PC. (2010) Identification of tyrosine-phosphorylated proteins associated with lung cancer metastasis using label-free quantitative analyses. J Proteome Res. 9(8):4102-12. 

Chiou SH, Huang CH, Lee IL, Wang YT, Liu NY, Tsay YG, Chen YJ. (2010) Identification of in vivo phosphorylation sites of lens proteins from porcine eye lenses by a gel-free phosphoproteomics approach. Mol Vis. 16:294-302. 

Rajkumar R, Ilayaraja R, Liao CC, Archunan G, Achiraman S, Prakash S, Ng WV, Tsay YG. (2010) Detection of alpha(2u)-globulin and its bound putative pheromones in the preputial gland of the Indian commensal rat (Rattus rattus) using mass spectrometry. Rapid Commun Mass Spectrom. 24(6):721-8. 

Yeih DF, Yeh HI, Lin LY, Tsay YG, Chiang FT, Tseng CD, Tseng YZ. (2011) Enhanced activity and subcellular redistribution of myocardial hexokinase after acute myocardial infarction. Int J Cardiol. 149(1):74-9. 

Wu HY, Tseng VS, Chen LC, Chang YC, Ping P, Liao CC, Tsay YG, Yu JS, Liao PC. (2009) Combining alkaline phosphatase treatment and hybrid linear ion trap/Orbitrap high mass accuracy liquid chromatography-mass spectrometry data for the efficient and confident identification of protein phosphorylation. Anal Chem. 81(18):7778-87. 

Wu TF, Huang WC, Chen YC, Tsay YG, Chang CS. (2009) Proteomic investigation of the impact of oxygen on the protein profiles of hyaluronic acid-producing Streptococcus zooepidemicus. Proteomics. 9(19):4507-18. 

Wu CH, Yeh SH, Tsay YG, Shieh YH, Kao CL, Chen YS, Wang SH, Kuo TJ, Chen DS, Chen PJ. (2009) Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication. J Biol Chem. 284(8):5229-39. 

Hsu WM, Lee H, Juan HF, Shih YY, Wang BJ, Pan CY, Jeng YM, Chang HH, Lu MY, Lin KH, Lai HS, Chen WJ, Tsay YG, Liao YF, Hsieh FJ. (2008) Identification of GRP75 as an independent favorable prognostic marker of neuroblastoma by a proteomics analysis. Clin Cancer Res. 14(19):6237-45. 

Cheng BC, Chang CP, Tsay YG, Wu TF, Hsu CY, Lin MT. (2008) Body cooling causes normalization of cardiac protein expression and function in a rat heatstroke model. J Proteome Res. 7(11):4935-45. 

Chen YS, Huang WH, Hong SY, Tsay YG, Chen PJ. (2008) ERK1/2-mediated phosphorylation of small hepatitis delta antigen at serine 177 enhances hepatitis delta virus antigenomic RNA replication. J Virol. 82(19):9345-58. 

Touré A, Mzali R, Liot C, Seguin L, Morin L, Crouin C, Chen-Yang I, Tsay YG, Dorseuil O, Gacon G, Bertoglio J. (2008) Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase. FEBS Lett. 582(8):1182-8. 

Wu TF, Ku WL, Tsay YG. (2007) Proteome-based diagnostics and prognosis of bladder transitional cell carcinoma. Expert Rev Proteomics. 4(5):639-47.

Huang C, Chang SC, Yu IC, Tsay YG, Chang MF. (2007) Large hepatitis delta antigen is a novel clathrin adaptor-like protein. J Virol. 81(11):5985-94. 

Huang CH, Tsai HH, Tsay YG, Chien YN, Wang SL, Cheng MY, Ke CH, Chen CW. (2007) The telomere system of the Streptomyces linear plasmid SCP1 represents a novel class. Mol Microbiol. 63(6):1710-8.

Chang YW, Chen SC, Cheng EC, Ko YP, Lin YC, Kao YR, Tsay YG, Yang PC, Wu CW, Roffler SR. (2005) CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells. Int J Cancer. 116(2):243-52. 

Tsay YG, Chen CC, Hu ST. (2005) Identification of the -1 translational frameshift sites using a liquid chromatography-tandem mass spectrometric approach. Anal Biochem. 339(1):83-93. 

Lai LP, Lin JL, Lin CS, Yeh HM, Tsay YG, Lee CF, Lee HH, Chang ZF, Hwang JJ, Su MJ, Tseng YZ, Huang SK. (2004) Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation. J Cardiovasc Electrophysiol. 15(2):214-23. 

Mu JJ, Tsay YG, Juan LJ, Fu TF, Huang WH, Chen DS, Chen PJ. (2004) The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis. Virology. 319(1):60-70. 

Hsu RB, Tsay YG, Wang SS, Chu SH. (2003) Management of aortic aneurysm infected with Salmonella. Br J Surg. 90(9):1080-4. 

Hsu RB, Tsay YG, Lee CM, Chen RJ, Wang SS, Chu SH. (2003) Soluble inflammatory markers in coronary sinus and peripheral blood of heart transplant recipients. Clin Transplant. 17(4):331-7.

Wang YH, Tsay YG, Tan BC, Lo WY, Lee SC. (2003) Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem. 278(28):25568-76. 

Hsu RB, Tsay YG, Chen RJ, Chu SH. (2003) Risk factors for primary bacteremia and endovascular infection in patients without acquired immunodeficiency syndrome who have nontyphoid salmonellosis. Clin Infect Dis. 36(7):829-34. 

Hsu RB, Tsay YG, Wang SS, Chu SH. (2002) Surgical treatment for primary infected aneurysm of the descending thoracic aorta, abdominal aorta, and iliac arteries. J Vasc Surg. 36(4):746-50. 

Lin WC, Shen BJ, Tsay YG, Yen HC, Lee SC, Chang CJ. (2002) Transcriptional activation of C/EBPbeta gene by c-Jun and ATF2. DNA Cell Biol. 21(8):551-60. 

Chen HC, Lin WC, Tsay YG, Lee SC, Chang CJ. (2002) An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K. J Biol Chem. 277(43):40403-9. 

Chiu CM, Tsay YG, Chang CJ, Lee SC. (2002) Nopp140 is a mediator of the protein kinase A signaling pathway that activates the acute phase response alpha1-acid glycoprotein gene. J Biol Chem. 277(42):39102-11. 

Chen CW, Tsay YG, Wu HL, Lee CH, Chen DS, Chen PJ. (2002) The double-stranded RNA-activated kinase, PKR, can phosphorylate hepatitis D virus small delta antigen at functional serine and threonine residues. J Biol Chem. 277(36):33058-67.

Yang CC, Huang CH, Li CY, Tsay YG, Lee SC, Chen CW. (2002) The terminal proteins of linear Streptomyces chromosomes and plasmids: a novel class of replication priming proteins. Mol Microbiol. 43(2):297-305.

Chia JS, Chang LY, Shun CT, Chang YY, Tsay YG, Chen JY. (2001) A 60-kilodalton immunodominant glycoprotein is essential for cell wall integrity and the maintenance of cell shape in Streptococcus mutans. Infect Immun. 69(11):6987-98.

Tsay YG, Wang YH, Chiu CM, Shen BJ, Lee SC. (2000) A strategy for identification and quantitation of phosphopeptides by liquid chromatography/tandem mass spectrometry. Anal Biochem. 287(1):55-64. 

Tsay YG, Lin NY, Voss PG, Patterson RJ, Wang JL. (1999) Export of galectin-3 from nuclei of digitonin-permeabilized mouse 3T3 fibroblasts. Exp Cell Res. 252(2):250-61. 

Voss PG, Tsay YG, Wang JL. (1994) Galectin-3: differential accumulation of distinct mRNAs in serum-stimulated mouse 3T3 fibroblasts. Glycoconj J. 11(4):353-62.