Graduate Institute of Biomedical Sciences

Research directions and laboratory features

Our laboratory focuses on quantitative proteomics and mass spectrometry-based approaches to systematically investigate cancer-related biomarkers, tumor antigens, and tumor immunological mechanisms. The overarching goal is to translate fundamental discoveries into clinical applications by developing analytical platforms for molecular diagnostics and targeted or immunotherapeutic strategies. Guided by a research framework of “analytical tool development – molecular mechanism elucidation – clinical problem-driven research,” we integrate proteomics, mass spectrometry, bioinformatics, and artificial intelligence into a sustainable, long-term research platform. Current research directions：

1.      Cancer biomarker discovery and validation in body fluids and tissues. With a particular focus on oral cancer, we employ multiplexed targeted mass spectrometry to establish precise quantification for low-abundance proteins, further enhanced by anti-peptide monoclonal antibodies to improve sensitivity and specificity. By accounting for inter-individual variability, daily physiological fluctuations, and comparisons across different body fluids, we progressively build clinically relevant quantitative reference frameworks and demonstrate the potential of saliva as a non-invasive diagnostic specimen.

2.      Immunopeptidomics-based investigation of tumor antigens and tumor immunity. By integrating multi-omics data, including proteomics and genomics, we characterize antigenic peptides presented on tumor cell surfaces, tumor-secreted proteins, and their interactions with the immune microenvironment. These studies address immune-hot and immune-cold tumor phenotypes, mechanisms of tumor progression, and their implications for immunotherapy response and patient stratification, providing a molecular basis for precision treatment strategies.

3.      Development of key technologies and analytical platforms for precision analysis. We continuously advance multiplexed targeted quantitative proteomic workflows and nucleic acid aptamer selection and optimization. By incorporating artificial intelligence and bioinformatics, we establish automated and standardized tools for mass spectrometric chromatogram analysis to improve data-processing efficiency, reduce operator bias, and enhance clinical applicability. In addition, structural modeling and sequence design are employed to expand the use of aptamers in molecular detection and targeted therapeutic applications.

Publications

1. Wu CS, Li HP, Hsieh CH, Lin YT, Yi-Feng Chang I, Chung AK, Huang Y, Ueng SH, Hsiao YC, Chien KY, Luo JD, Chen CH, Liao WC, Hung JL, Yuan SN, OuYang CN, Chiang WF, Chien CY, Chuang HC, Chu LJ, Liu H, Yang CY, Robles AI, Rodriguez H, Lin HH, Yang HY, Hsueh C, Chang KP, Yu JS, and Chang YS. (2025) Integrated multi-omics analyses of oral squamous cell carcinoma reveal precision patient stratification and personalized treatment strategies. Cancer Lett 614, 217482.
   
   2. Liu CC, Hsiao YC, Lai WJ, Chiou CC, Chu LJ, Lin YT, Liu JC, and Yu JS. (2024) Development and optimization of a DNA aptamer to delay beta-bungarotoxin-induced lethality in a rodent model. Int J Biol Macromol 270 (Pt 2), 132240.
   
   3. Lee CC, Lin YC, Pan TY, Yang CH, Li PH, Chen SY, Gao JJ, Yang C, Chu LJ, Huang PJ, Yeh YM, Tang P, Chang YS, Yu JS, and Hsiao YC. (2023) HeapMS: An Automatic Peak-Picking Pipeline for Targeted Proteomic Data Powered by 2D Heatmap Transformation and Convolutional Neural Networks. Anal Chem 95 (42), 15486–15496.
   
   4. Hsiao YC, Chi LM, Chien KY, Chiang WF, Chen SF, Chuang YN, Lin SY, Wu CC, Chang YT, Chu LJ, Chen YT, Chia SL, Chien CY, Chang KP, Chang YS, and Yu JS. (2017) Development of a Multiplexed Assay for Oral Cancer Candidate Biomarkers Using Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry. Mol Cell Proteomics 16 (10), 1829–1849.
   
   5. Yu JS, Chen YT, Chiang WF, Hsiao YC, Chu LJ, See LC, Wu CS, Tu HT, Chen HW, Chen CC, Liao WC, Chang YT, Wu CC, Lin CY, Liu SY, Chiou ST, Chia SL, Chang KP, Chien CY, Chang SW, Chang CJ, Young JD, Pao CC, Chang YS, and Hartwell LH. (2016) Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci U S A 113 (41), 11549–11554.
   
   6. Liu CC, Yang YH, Hsiao YC, Wang PJ, Liu JC, Liu CH, Hsieh WC, Lin CC, and Yu JS. Rapid and Efficient Enrichment of Snake Venoms from Human Plasma Using a Strong Cation Exchange Tip Column to Improve Snakebite Diagnosis. Toxins (Basel) 2021, 13 (2).
   
   7. Liu CC, Wu CJ, Hsiao YC, Yang YH, Liu KL, Huang GJ, Hsieh CH, Chen CK, and Liaw GW. Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A2 activity with varespladib. J Proteomics 2020, 234, 104084.
   
   8. Lin YH, Wu CC, Su WT, Tseng PC, Hsueh YY, Hsiao YC, Chang KP, Yu JS, and Chuang YJ. Target peptide enrichment microfluidic chip for rapid detection of oral squamous cell carcinoma using stable isotope standards and capture by anti-peptide antibodies. Sensors and Actuators B: Chemical 2020, 322, 128607.
   
   9. Hsiao YC, Lin SY, Chien KY, Chen SF, Wu CC, Chang YT, Chi LM, Chu LJ, Chiang WF, Chien CY, Chang KP, Chang YS, and Yu JS. An immuno-MALDI mass spectrometry assay for the oral cancer biomarker, matrix metalloproteinase-1, in dried saliva spot samples. Anal Chim Acta 2020, 1100, 118-130.
   
   10. Chi LM#, Hsiao YC#, Chien KY#, Chen SF, Chuang YN, Lin SY, Wang WS, Chang IY, Yang C, Chu LJ, Chiang WF, Chien CY, Chang YS, Chang KP, and Yu JS. Assessment of candidate biomarkers in paired saliva and plasma samples from oral cancer patients by targeted mass spectrometry. J Proteomics 2020, 211, 103571.
   
   11. Liu CC, Yu JS, Wang PJ, Hsiao YC, Liu CH, Chen YC, Lai PF, Hsu CP, Fann WC, and Lin CC. Development of sandwich ELISA and lateral flow strip assays for diagnosing clinically significant snakebite in Taiwan. PLoS Negl Trop Dis 2018, 12 (12), e0007014.
   
   12. Liu CC, Lin CC, Hsiao YC, Wang PJ, and Yu JS. Proteomic characterization of six Taiwanese snake venoms: Identification of species-specific proteins and development of a SISCAPA-MRM assay for cobra venom factors. J Proteomics 2018, 187, 59-68.
   
   13. Hsiao YC, Chu LJ, Chen YT, Chi LM, Chien KY, Chiang WF, Chang YT, Chen SF, Wang WS, Chuang YN, Lin SY, Chien CY, Chang KP, Chang YS, and Yu JS. Variability Assessment of 90 Salivary Proteins in Intraday and Interday Samples from Healthy Donors by Multiple Reaction Monitoring-Mass Spectrometry. Proteomics Clin Appl 2018, 12 (2).
   
   14. Hsiao YC, Chu LJ, Chen JT, Yeh TS, and Yu JS. Proteomic profiling of the cancer cell secretome: informing clinical research. Expert Rev Proteomics 2017, 14 (9), 737-756.
   
   15. Hsiao YC, Chi LM, Chien KY, Chiang WF, Chen SF, Chuang YN, Lin SY, Wu CC, Chang YT, Chu LJ, Chen YT, Chia SL, Chien CY, Chang KP, Chang YS, and Yu JS. Development of a Multiplexed Assay for Oral Cancer Candidate Biomarkers Using Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry. Mol Cell Proteomics 2017, 16 (10), 1829-1849.
   
   16. Yu JS#, Chen YT#, Chiang WF#, Hsiao YC#, Chu LJ#, See LC, Wu CS, Tu HT, Chen HW, Chen CC, Liao WC, Chang YT, Wu CC, Lin CY, Liu SY, Chiou ST, Chia SL, Chang KP, Chien CY, Chang SW, Chang CJ, Young JD, Pao CC, Chang YS, and Hartwell LH. Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci U S A 2016, 113 (41), 11549-11554.
   
   17. Chen H#, Hsiao YC#, Chiang SF, Wu CC, Lin YT, Liu H, Zhao H, Chen JS, Chang YS, and Yu JS. Quantitative analysis of wild-type and V600E mutant BRAF proteins in colorectal carcinoma using immunoenrichment and targeted mass spectrometry. Anal Chim Acta 2016, 933, 144-155.