# The role of GLUT3 in the genetics of autoimmunity and immunometabolism

> **NIH NIH K01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2021 · $127,710

## Abstract

PROJECT SUMMARY/ABSTRACT
Rheumatoid arthritis (RA) is the most common adult form of inflammatory polyarthritis and is associated with
substantial disability and increased mortality. Current biologic therapies are effective in a subset of patients,
but there is a clear need for improved therapeutic approaches. Deletion of the SLC2A3 gene (encoding the
GLUT3 glucose transporter protein) on chromosome 12 is strongly protective for RA in humans. In order to
harness the protective effect of this genetic variant for use in developing preventative or therapeutic measures
for RA, it is crucial to understand the cell types, cell functions and disease pathogenic mechanisms altered by
SLC2A3 haploinsufficiency. The reduced risk for RA in deletion-carriers suggests that corresponding reduced
expression of GLUT3 in cells dependent on GLUT3 for their function reduces risk for RA development; we
have shown reduced expression in both T cells and myeloid cell types of deletion-carriers. As CD4 T cells are
considered to be a key driver in the initiation of RA, and recent literature indicate that GLUT3 is required for
normal T cell proliferation, our primary hypothesis is that the arthritis protective mechanism is T cell dependent.
The specific aims are to: 1) elucidate the role of Glut3 haploinsufficiency on the development of mouse models
of RA, 2) study the requirement for Glut3 sufficiency in CD4+ T cell functions in Slc2a3 conditional knockout
mice 3) identify the cell-type intrinsic mechanism of the protective effect of Slc2a3 hemizygosity, and 4)
determine requirement of GLUT3 sufficiency for human CD4+ T cell functions and RA-like phenotypes.
The above abstract constitutes the revised research proposal component of a K01 career development award
application of Dr. Kim Simpfendorfer. Together with the career development plan, this proposal is designed to
allow Dr. Simpfendorfer the support and foundation to investigate the validity of GLUT3 as a therapeutic target
in RA. Specifically, Dr. Simpfendorfer will receive training and mentorship in research management, leadership
and animal models of RA as well as further training in autoimmune disease pathogenesis in mouse and human
systems. The achievement of these goals will be accomplished through the mentorship from Dr. Peter K
Gregersen, and input from the advisory committee of Drs. Betty Diamond, Laurence Morel, Sun Jung Kim and
Yong Rui Zou. Additionally, Kim will receive technical training in animal models of arthritis from Drs. Max
Brenner, Anne Davidson and Myoungsun Son. The Feinstein Institute for Medical Research is an ideal
institutional environment for Dr. Simpfendorfer's research and career development due to training and
mentoring resources, unique human resources such as the Genotype and Phenotype Registry, and the cross-
disciplinary expertise of the proposed mentor, advisory committee and institutional faculty. Furthermore, the
Feinstein Institute is adequately equipped with the required facili...

## Key facts

- **NIH application ID:** 10240294
- **Project number:** 5K01AR071502-04
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Kim R Simpfendorfer
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $127,710
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240294

## Citation

> US National Institutes of Health, RePORTER application 10240294, The role of GLUT3 in the genetics of autoimmunity and immunometabolism (5K01AR071502-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240294. Licensed CC0.

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