# Systems Biology of Glycosylation

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $538,813

## Abstract

This is the renewal application of a grant that has been supported as part of the NHLBI Systems Biology program.
It deals with the subject of glycosylation, a ubiquitous and complex post-translational modification in mammalian
cells. Glycans decorate a vast majority of mammalian proteins. They absolutely control or fine-tune a number of
cellular processes in higher organisms including development, immunity, inflammation, bleeding and metastasis.
Glycan structures change due to alterations in cell metabolism, development and signaling events that perturb
the underlying transcriptome. A systematic understanding of the factors (genetic and epigenetic) controlling
glycosylation is currently unavailable. This is however important for two reasons: i. Such knowledge can help
establish quantitative links between different cell systems, so that knowledge gained in the study of one system
can be applied to predict the outcome in another. ii. Gene transcript measurements are now being used in clinical
diagnostics, and the advent of next generation sequencing (NGS) has dramatically reduced the cost of such
assays. If a relation between changes in the pattern of gene expression and alterations in glycan structures is
established, disease-associated glycan biomarkers may be assayed using standard gene sequencing methods.
This can enable both early diagnosis and patient stratification during precision medicine applications. Based on
the above, the current proposal addresses the hypothesis that “Coupling systems based quantitative,
analytical experimentation with model building can help relate cellular glycomics changes to the
underlying transcriptome”. This proposition will be tested by performing a series of studies using blood
leukocytes involved in innate immunity and by relating findings to inflammatory leukocyte-endothelial cell
adhesion mechanics. The specific aims are: 1. To develop a blood glycan atlas using single-cell analysis on
NGS platform and glycoProbe based mass spectrometry. This aim will result in a relational database that
describes the glycoEnzymes regulating the biosynthesis of specific glycan structures in three myeloid/monocytic
blood cell lines, primary human blood and in CD34+ hematopoietic stem/progenitor cells (HSPC). 2: To develop
a complementary experiment-modeling framework to relate glycogene expression to glycan structure. This aim
extends concepts in Aim 1, only focusing on blood cells that are being differentiated down neutrophil or
macrophage lineages. Emerging data will yield glycogene regulatory network maps that identify novel controllers
of cellular glycosylation profile. 3: To test the roles of selected small molecules, transcription factors (TFs) &
glycogene checkpoints during leukocyte-endothelial cell adhesion ex vivo and in vivo. Here, we determine the
ability of data-driven computer predictions and molecular studies, to identify new checkpoints regulating human
inflammatory leukocyte adhesion. Overall, the study scal...

## Key facts

- **NIH application ID:** 10810646
- **Project number:** 5R01HL103411-12
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** SRIRAM NEELAMEGHAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,813
- **Award type:** 5
- **Project period:** 2011-09-05 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810646

## Citation

> US National Institutes of Health, RePORTER application 10810646, Systems Biology of Glycosylation (5R01HL103411-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10810646. Licensed CC0.

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