# ST8Sia6 modulation of diabetes

> **NIH NIH F30** · MAYO CLINIC ROCHESTER · 2022 · $46,952

## Abstract

Project summary:
Type 1 diabetes affects millions of individuals globally, and is a significant cause of morbidity and mortality.
The autoimmune process behind this disease is not fully understood, complicating attempts to prevent or cure
it. Islet transplantation is a potentially curative approach, but remains hindered by numerous adverse
complications, including lifelong immunosuppression required after the procedure. Thus, the objective of this
grant is to investigate an immunomodulatory approach for mitigating autoimmunity, with the goals of better
understanding the aberrant immune response in type 1 diabetes and contributing to an improved therapeutic
approach for islet replacement. Cancers and pathogens have been noted to upregulate sialyltransferases and
engage inhibitory Siglec receptors to dampen immune rejection. Previous studies in the lab found that islet
resident macrophages express the inhibitory Siglec-E receptor, which binds sialic acid residues generated by
the sialyltransferase ST8Sia6. This leads to the central hypothesis that induced ST8Sia6 expression in the
beta cells of the islet can protect against autoimmune rejection. To test this, we have developed a novel
mouse on the non-obese diabetic background that expresses ST8Sia6 in a beta cell specific manner, and have
shown robust protection from disease. The central hypothesis will be addressed in two specific aims. The
mechanistic basis of protection from spontaneous and induced autoimmunity will be explored. Immune profiling
via flow cytometry will help elucidate the cellular and molecular events protecting from autoimmune activity.
This project recognizes the complex dynamics of the immune response and considers both innate and
adaptive mediators of autoimmunity in investigating a novel immunomodulatory path. Additionally, the potential
therapeutic applications of this work will be tested. Our genetic model includes a tetracycline-off parameter,
allowing for temporal studies investigating the minimum required time of ST8Sia6 expression for robust
protection or the ability of ST8Sia6 to alter the autoimmune disease process once initiated. We will also employ
novel islet transplantation models to determine whether ST8Sia6 expressing beta cells can restore glycemic
control without immunosuppression. Ultimately, this work will contribute to improved understanding of
autoimmunity and a potentially tissue-intrinsic approach to avoid immune rejection.

## Key facts

- **NIH application ID:** 10414792
- **Project number:** 5F30DK127564-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Justin Choe
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,952
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414792

## Citation

> US National Institutes of Health, RePORTER application 10414792, ST8Sia6 modulation of diabetes (5F30DK127564-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414792. Licensed CC0.

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