# Advancing top-down proteomics with capillary electrophoresis-mass spectrometry

> **NIH NIH R35** · MICHIGAN STATE UNIVERSITY · 2024 · $583,095

## Abstract

Project Summary
The research of the Sun group can be divided into two directions. In the first direction, the Sun group
focuses on the development of novel capillary electrophoresis-mass spectrometry (CE-MS)
techniques to advance bottom-up proteomics (BUP, peptide-centric), top-down proteomics (TDP,
proteoform-centric), and native proteomics (protein complex-centric) towards complete proteome
coverage of human cells with single-cell resolution. CE-MS is a powerful analytical tool for the highly
sensitive characterization of peptides, proteoforms, and protein complexes in complex biological
samples. In the second direction, the Sun group is applying the CE-MS techniques to developmental
biology and cancer biology. For developmental biology, we are pursuing a better understanding of the
roles played by specific proteins, proteoforms, and protein complexes in modulating the important
events during early vertebrate embryogenesis (i.e., early cellular differentiation and zygotic genome
activation (ZGA)). For cancer biology, we aim to discover new proteoform biomarkers of colorectal
cancer (CRC) metastasis by quantitative TDP studies of CRC cell lines and tumors.
In this MIRA application, the Sun group will advance CE-MS-based TDP techniques to achieve the
first draft of the proteoform atlas of a human cancer cell line (i.e., HeLa cells) and enable TDP
measurement of a few even single human cells. The Sun group will also apply the novel techniques
to developmental biology to discover crucial proteoforms that modulate early cellular differentiation
and ZGA during early vertebrate embryogenesis via quantitative TDP studies of zebrafish embryos
and blastomeres. The proteoform atlas of HeLa cells will contain at least one intact proteoform per
protein-coding gene, and it will be an extremely valuable resource for fundamental and translational
research. The generation of the first proteoform atlas of human cells will be a pivotal step toward the
“Human Proteoform Project”. The novel CE-MS techniques will play crucial roles in advancing TDP
toward the comprehensive characterization of proteoforms in various biological systems. The TDP
studies of zebrafish embryos and blastomeres will provide new insights into the roles played by
specific proteoforms in modulating early cellular differentiation and ZGA. The single-cell TDP
technique can be applied to various biological fields, e.g., cancer biology, developmental biology, and
neuroscience, to better our understanding of cell-to-cell heterogeneity.

## Key facts

- **NIH application ID:** 10842609
- **Project number:** 1R35GM153479-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Liangliang Sun
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $583,095
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842609

## Citation

> US National Institutes of Health, RePORTER application 10842609, Advancing top-down proteomics with capillary electrophoresis-mass spectrometry (1R35GM153479-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10842609. Licensed CC0.

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