# ST6Gal-1 Sialyltransferase in Inflammation

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE CORP · 2020 · $670,072

## Abstract

PROJECT ABSTRACT
There is increasing awareness of glycans participating in the communication of critical niche-cell and cell-cell
information. A growing body of evidence implicates the 2,6-sialylation of Gal(β1,4)GlcNAc termini, mediated
by the sialyltransferase ST6Gal-1, as a central player in the regulation of diverse events including cell death,
integrin-1 function, stem cell maintenance, susceptibility to radio- and chemo-agents, myelopoiesis, and
inflammation. Canonically, glycosylation is mediated by glycosyltransferases, including ST6Gal-1, residing
within the ER-Golgi secretory apparatus of the same cells that produce them. However a significant pool of
extracellular ST6Gal-1 exists, especially in the blood. Changes in the extrinsic ST6Gal-1 pool are associated
with diverse pathologic conditions relating to stress and inflammation, and malignancies where elevated levels
generally predict poorer patient outcomes.
We observed that deficiency in circulating ST6Gal-1 results in an overly exuberant inflammatory response,
which led to the overarching hypothesis that extracellular ST6Gal-1 remodels glycans on target immune cell
surfaces, dampening response to inflammatory signals. Additional premise in support are: i) mature myeloid
and marrow hematopoietic progenitor cells are targets of extrinsic ST6Gal-1 sialylation in vivo and in vitro; ii)
extrinsic ST6Gal-1 suppresses G-CSF driven granulopoiesis; (iii) reduces M-CSF dependent generation of
macrophages; (iv) decreases inflammatory cytokine expression and release by macrophage stimulated with
LPS; and v) intravenous injection of recombinant ST6Gal-1 (rST6G) significantly ameliorates severe local and
systemic inflammation in vivo. To acquire insight into this previously overlooked glycosylation mediated
regulation of inflammation, three aims are proposed to examine i) which aspects of inflammatory cell biology
are affected by extrinsic ST6Gal-1; ii) how does extrinsic ST6Gal-1 exert this action; and iii) what is the efficacy
of rST6G in treating severe inflammation. The impact from the proposed work lies in the novelty of the
previously overlooked extrinsic glycosylation axis, the ability of extrinsic ST6Gal-1 to suppress inflammation,
and the innovation in the clinical potential of recombinant ST6Gal-1 to treat severe inflammatory conditions.

## Key facts

- **NIH application ID:** 9990683
- **Project number:** 5R01AI140736-03
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Joseph TY Lau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $670,072
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990683

## Citation

> US National Institutes of Health, RePORTER application 9990683, ST6Gal-1 Sialyltransferase in Inflammation (5R01AI140736-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990683. Licensed CC0.

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