Our Research

Structural lipidomics is a rapidly evolving field, driven by the immense structural diversity of the lipidome, which encompasses over 40,000 documented species. This complexity demands innovative MS/MS approaches capable of resolving subtle isomeric differences. Over the past decade, numerous isomer-resolved MS/MS techniques have been developed and several have been incorporated into commercial mass spectrometers, greatly expanding access to deep structural lipidomic profiling. We anticipate that isomer-resolved MS/MS will catalyze advances in single-cell, spatial, temporal, clinical, and functional lipidomics by delivering isomer-level structural resolution in these emerging frontiers.

图片2.png

1. Characterization of lipids at detailed structural levels. We established PB-MS/MS methods for the identification and quantitation of C=C position isomers across more than 20 lipid classes. We developed a thiyl radical-catalyzed C=C cis-trans isomerization approach, integrated with online PB-MS/MS, enabling simultaneous characterization of lipid C=C geometry (Z/E) and position. Furthermore, we are developing novel radical-induced dissociation (RDD) MS/MS methods for in-depth analysis of sn-isomers, methyl branching, and hydroxyl group positions in complex lipids. （Reviews links: Acc. Chem. Res. 2021, 54, 3873−3882；J. Lipid Res. 2022, 63, 100219 ; Anal. Chem. 2025, 97, 4275 ; Anal. Chim. Acta, 2025, 344456）

图片1.png


2. Selective enrichment for low-abundance lipids. We developed selective enrichment methods for the glycosphingolipidome using magnetic titanium dioxide nanoparticles (TiO₂ MNPs). This strategy improved the detection dynamic range by 1–3 orders of magnitude, enabling the construction of multi-level structural maps encompassing over 1,000 sphingolipid species in brain tissue, human plasma, and breast cancer cells.


图片3.png


3. Establishment of structural lipidomics workflows and their biomedical applications. We developed a photochemical microflow reactor (commercialized as the Omega Analyzer) and established lipidomic workflows integrating LC, online PB derivatization, and MS/MS. By further coupling with ion mobility spectrometry (IMS), we developed a deep lipidomic analysis system with automated data annotation. These workflows enable porifling over a thousand unsaturated lipid species at C=C location level from as little as 10⁵ cells, 10 mg tissue, 20 µL serum, or human sebum. Applications include human glioma subtype classification via sphingolipidome analysis, revealing downregulation of CerS2 and FA2H, and identification of sn-1 selectivity of LPCAT1 in hepatocellular carcinoma.


图片4.png

图片5.png

图片6.png


4. Methods for probing lipid-protein interactios. We developed novel photo-tagging probes to capture weak interactions between model transmembrane peptides and annular lipids. Subsequent LC-MS/MS analysis of the cross-linked products enabled the construction of tagging profiles and determination of the penetration depth of targeted amino acid residues within the lipid bilayer. Combined with all-atom molecular dynamics simulations, we revealed the structural details of hydrophobic mismatches induced by model transmembrane peptides and determined the identity and stoichiometry of annular lipids surrounding individual peptides. In collaboration with the groups of Prof. Yuanzheng He at Harbin Institute of Technology and Eric Xu at the Shanghai Institute of Materia Medica, we identified the structures of lipid ligands for multiple membrane proteins using isomer-resovled MS/MS.


lipidprotein.png

PB-MS/MS developed by our group

Advances of PB-MS/MS by other research groups around the world.(2017-2026)