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Oral Sessions
Day 2, June 23（Mon.） 14:10-14:25
Room C (Top of Yaima)
- 2C-O2-1410
Mapping Nanoscale-to-Single Cell Proteome Landscape and Beyond towards Precision Oncology
(Academia Sinica)
oYu-Ju Chen
Large-scale clinical proteomics and PTMomics provide a molecular view of disease, driving precision medicine through biomarker discovery, disease subtyping, and identification of druggable pathways. However, clinical proteomics faces challenges in achieving high sensitivity across disease stages and deep coverage to capture disease biology, particularly in body fluid proteomics, where abundant proteins hinder detection of low-abundance biomarkers.
To advance analytical performance in clinical proteomics, we explored the data-independent acquisition mass spectrometry (DIA MS) for rapid and deep proteomics and phosphoproteomics profiling from large-scale profiling down to single cell landscape. We developed a rapid one-pot workflow for microscale phosphoproteomics (1000–10 cells), detecting >22,000 phosphopeptides from sub-μg lysates, revealing Hippo-EGFR-ERBB pathway interactions driving EGFR-TKI resistance. To explore cellular heterogeneity, we introduced a microfluidics-based chip platform enabling ultra-sensitive nanoscale-to-single-cell phosphoproteomic profiling. Using the integrated proteomics chip (iProChip), we uncovered cytoskeletal remodeling and cytokeratin heterogeneity in patient-derived cells, stratifying adenocarcinoma-squamous cell carcinoma subtypes and identifying alternative therapies for late-stage patients. Finally, I will present a high-throughput proteomics pipeline leveraging a modified Thermo Scientific™ Orbitrap™ Astral™ mass spectrometer with enhanced speed and sensitivity for plasma proteomics.