# Uniting Mass Spectrometry and Glycoscience to Investigate Cancer Biology

> **NIH NIH K00** · STANFORD UNIVERSITY · 2020 · $87,015

## Abstract

Project Summary/Abstract.
 Protein glycosylation is a prevalent, chemically complex, and biologically diverse post-translational
modification (PTM) involved in a wide array of cellular functions. Glycosylation plays essential roles in regulation
of cellular proliferation and metabolic processes, and changes in glycosylation are universal features of
malignant transformation and tumor progression. Metastasis, or the spread of cancer to non-adjacent parts of
the body, is a particularly insidious characteristic of many aggressive cancers. Evidence suggests that specific
changes in glycosylation may reflect fitness of tumor progression and metastatic potential, making global
characterization of glycosylation crucial to understanding the molecular basis of cancer aggression/metastasis.
 Despite the critical importance of glycosylation in cancer research, current technology for characterizing
this PTM is underdeveloped. Mass spectrometry (MS) is the gold standard for analysis of PTMs, but the chemical
complexity of glycosylation has significantly slowed progress of MS technology relative to other modifications.
This proposal introduces activated-ion electron transfer dissociation (AI-ETD) as a new tandem MS approach
for comprehensive characterization of intact glycopeptides. The combination of infrared photo-activation and
electron-driven radical fragmentation in AI-ETD generates peptide sequence and glycan composition information
in a single tandem MS event. This eliminates multiple tandem MS scans per precursor that are necessary in
current approaches, improving sensitivity and effectively doubling throughput. In this application, AI-ETD will be
implemented on the newest generation of Orbitrap MS systems (Fusion Lumos) to capitalize on its robust data-
acquisition platform, and high-throughput AI-ETD methods for glycoproteomic experiments will be developed.
These methods will be utilized in glycoproteomic characterization of three isogenic human cancer cell lines that
represent non-, intermediate-, and highly-metastatic forms of melanoma. By enabling characterization of
hundreds of glycosites and thousands of glycans, this work will be the most comprehensive glycoproteomic
comparison of cancer cell lines yet, allowing investigation of glycosylation signatures of cancer aggression with
unprecedented breadth and depth across the glycoproteome. This data set will advance the understanding of
cancer metastasis at a molecular level and reveal new insights into the role of glycosylation in cancer.
 Upon completion of this project, I will seek postdoctoral training in a preeminent cancer glycobiology
laboratory, complementing the technology development focus of my graduate research. The combination of
expertise in MS instrumentation development and the glycoscience of cancer will uniquely equip me for a prolific
career as an independent scientist at the interface of biology and technology and the forefront of cancer research.

## Key facts

- **NIH application ID:** 9982272
- **Project number:** 5K00CA212454-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Nicholas M Riley
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $87,015
- **Award type:** 5
- **Project period:** 2018-09-13 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982272

## Citation

> US National Institutes of Health, RePORTER application 9982272, Uniting Mass Spectrometry and Glycoscience to Investigate Cancer Biology (5K00CA212454-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9982272. Licensed CC0.

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