# ST6Gal-1 Sialyltransferase in Inflammation

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE CORP · 2020 · $183,648

## Abstract

Project Summary (Supplement)
COVID-19 is a pandemic in which the high mortality rate is driven by high infectivity and rampant transmission
of the causative corona virus, SARS-CoV-2. The unpredictable and very rapid life-threatening deterioration in
some but not all viral-positive patients remains unsolved and requires immediate attention. Plasmapheresis,
used to treat patients with acute organ transplant rejection, ameliorates the severe symptoms of COVID-19
patients, suggesting a similar immune-related dysfunction in COVID-19. Emerging studies implicate altered
glycans and glycosylation as central but overlooked contributors in COVID-19 pathogenesis. Among these
studies: 1) Blood group A patients have significantly worse outcomes than blood group O; 2) the SARS-CoV-2
displays unique glycan structures, the TF and Tn antigens that are normally only expressed in cancer; 3)
engaging host sialic acid glyan epitopes to facilitate viral entry and dispersal is well document in related corona
viruses although not yet reported for SARS-CoV-2.
 Our preliminary data supports a glycosylation-axis in COVID-19 pathogenesis. Comparing 10 viral-positive
patients with 10 healthy volunteers, we showed patient plasma have 1) IgGs and IgMs directed again a number
of prominent cell surface glycan structures, including against TF and Tn antigens; and 2) a striking shift of anti-
ABO from predominantly IgG to IgM (p<0.001 with just 10 patients and 10 volunteers). Additional observations,
part of the ongoing parent NIAID-funded R01, identified a blood-borne glycan-modifying enzyme, ST6GAL1 with
pleiotropic functions in promoting Ig production, B cell maturation, facilitating transitional B cell survival during
selection, while attenuating inflammation by muting cytokine release from airway macrophages. We have also
reported that platelets as critical contributors to ST6GAL1 function, natural circulating ST6GAL1 levels fluctuate
depending on disease status, and that inoculation of recombinant ST6GAL1 mitigated acute airway inflammation
in mice.
 We propose using an increase number of patient and healthy donor plasma to expand upon the unique anti-
glycan antibodies and correlate with disease status. We will also address how glycosylation abnormalities drive
plate dysfunction in COVID19 by assessing the ability of patient anti-glycan antibodies to activate platelets.
These Aims should yield definitive insights into blood glycans in COVID-19. Future directions will test the utility
of glycans, glycan-mimetics, and/or recombinant glycan-modifying enzymes such as ST6GAL1 as therapeutic
modalities for COVID-19.

## Key facts

- **NIH application ID:** 10159705
- **Project number:** 3R01AI140736-02S1
- **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:** $183,648
- **Award type:** 3
- **Project period:** 2020-06-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159705

## Citation

> US National Institutes of Health, RePORTER application 10159705, ST6Gal-1 Sialyltransferase in Inflammation (3R01AI140736-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10159705. Licensed CC0.

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