PIPages
Labs

Liangliang Sun

Michigan State University, MI·Chemistry

One gene can give rise to many slightly different protein molecules called proteoforms. Each may differ through alternative processing or added chemical tags (post-translational modifications).

Fields

Chemistry

Biochemistry

Biology

Topics

top-down proteomics

proteoforms

capillary electrophoresis-mass spectrometry

Grants
2 known grants, through Apr 2029

What they work on

  1. Advance CE-MS top-down proteomics to build a first draft proteoform atlas of HeLa cells. The atlas will contain at least one intact protein form for every protein-coding gene.
  2. Develop CE-MS methods that measure intact proteins from a few or even single human cells. This would let researchers study cell-to-cell differences.
  3. Identify proteoforms that control early cell differentiation and zygotic genome activation, when the embryo turns on its own genes. Use quantitative top-down proteomics of zebrafish embryos and blastomeres.
  4. Build new analytical tools to raise top-down proteomics sensitivity about tenfold for small samples. Apply them to compare colorectal cancer cells before and after metastasis to find proteoform changes.
  5. Use quantitative top-down proteomics of Lynch syndrome tumors to reveal how mutations in DNA mismatch repair genes act at the level of intact protein forms.

More about the research

These versions can have very different jobs, yet most protein studies first chop proteins into small pieces, which loses this information. Top-down proteomics instead measures whole, intact proteins. Two projects develop more sensitive tools for this approach using capillary electrophoresis-mass spectrometry (CE-MS). CE-MS separates molecules in a thin capillary tube and then weighs them precisely in a mass spectrometer. The projects then apply these tools to early embryo development and colorectal cancer.

Why it matters

Colorectal cancer kills tens of thousands of people in the United States each year. Measuring intact protein forms in CRC cells and tumors could reveal proteoform biomarkers of metastasis. It could also clarify how faulty DNA repair genes drive Lynch syndrome, which may point to better therapies. A human proteoform atlas and single-cell methods could also give cancer, developmental and brain researchers a resource for studying how cells differ.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Advancing top-down proteomics with capillary electrophoresis-mass spectrometry

NIH · May 2024 – Apr 2029

Quantitative top-down proteomics of human colorectal cancer cells and tumors

NIH · Feb 2021 – Jan 2027

Closest labs

Si Wu

University of Alabama, AL·Chemistry

Develop and benchmark a 2D-RPLC-CE-MS/MS platform, which combines two separation steps with mass spectrometry, to screen intact proteoforms globally in single ovarian cancer spheroids.

Ryan Julian

University of California-Riverside, CA·Chemistry

Design and synthesize photoactivated chemical modifiers that install a weak link at chosen residues in a protein backbone, so the protein can be split at that spot on demand.

Upasna Sharma

University of California-Santa Cruz, CA·Biology

Determine whether Mettl7a1, a predicted RNA methyltransferase that adds methyl tags to RNA, is needed for minor zygotic genome activation and normal early development in mouse preimplantation embryos.

The school

Michigan State University: 28 labs on PI Pages, $932M a year on research, 555 research doctorates a year.

More about Michigan State University

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