Proteoform-Selective Imaging of Tissues Using Mass Spectrometry**

Manxi Yang, Hang Hu, Pei Su, Paul M. Thomas, Jeannie M. Camarillo, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Neil L. Kelleher, Julia Laskin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) for the proteoform-selective imaging of biological tissues. Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof-of-concept experiments demonstrate that nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.

Original languageEnglish (US)
Article numbere202200721
JournalAngewandte Chemie - International Edition
Issue number29
StatePublished - Jul 18 2022


  • Mass Spectrometry Imaging
  • On-Tissue Top-down Proteomics
  • Post-Translational Modifications
  • Proteoforms

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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