# Spatiotemporal and molecular determinants of autoimmune T cell stemness and differentiation in type I diabetes

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Type I Diabetes (T1D) is a T cell mediated autoimmune which is dramatically increasing in incidence. The
pathogenesis of T1D is complex and involves the infiltration of β cell-specific CD8 T cells into the pancreas and
progressive destruction of insulin-producing b cells, resulting in loss of glucose homeostasis. Utilizing the
clinically relevant Non-Obese Diabetic (NOD) mouse model of T1D, the Schietinger lab recently discovered a β
cell-specific stem-like CD8 T cell population in the pancreatic lymph node (pLN) which self-renews and gives
rise to differentiated progeny that migrate to the pancreas and destroy β cells; pancreatic T cells are short-lived
and stem-like T cells in the pLN must continuously seed the pancreas to sustain β cell destruction. In this
application I aim to understand the underlying molecular and cellular mechanisms that determine autoimmune
T cell differentiation. In aim 1, I will determine how and where stem-T cells self-renew and differentiate, employing
imaging cytometry and spatial transcriptomics technologies. In aim 2, I will define the functional role of
transcription factors associated with T cell stemness through gain and loss of function approaches. Finally, in
aim 3, I will ask whether perturbation of pLN intranodal positioning or inhibition of stem-T cell associated signaling
molecules disrupt autoimmune T cell differentiation and prevent T1D onset. These proposed studies are
designed to obtain a deep mechanistic understanding of the spatiotemporal and molecular factors that determine
autoimmune T cell differentiation which could lead to novel therapeutic targets for T1D and other T cell-mediated
autoimmune diseases.

## Key facts

- **NIH application ID:** 10995900
- **Project number:** 1F31DK141119-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Svetlana Dmitrievna Miakicheva
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-26 → 2027-08-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995900

## Citation

> US National Institutes of Health, RePORTER application 10995900, Spatiotemporal and molecular determinants of autoimmune T cell stemness and differentiation in type I diabetes (1F31DK141119-01). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10995900. Licensed CC0.

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