# Microphysiological systems for modeling autoimmunity in type 1 diabetes

> **NIH NIH UH3** · UNIVERSITY OF PENNSYLVANIA · 2022 · $1,124,415

## Abstract

SUMMARY
This proposal leverages our group’s complementary expertise in tissue-on-a-chip technology, immunology,
pluripotent cell derivation and differentiation, and islet biology to create robust systems containing human islet
cells, immune cells, and other features to recapitulate the process of islet autoimmunity in type I diabetes (T1D).
The UG3 phase of this proposal will improve upon already-robust microdevices and develop new cell lines and
assays that will enable studies of autoimmunity in an isogenic setting. The UH3 phase of this proposal will exploit
these tools and platforms to develop isogenic models that can be used to study immune-islet interactions. The
focus of the UH3 phase will be to investigate the determinants of islet infiltration and killing, and to determine the
effects of mutations in T1D-associated genes on this process. In addition, these in vitro systems will be used to
pilot the use of cellular therapies to interrupt the autoimmune attack of islets.
The specific aims of the UG3 phase are:
Aim 1: To expand the biomimetic platform
Aim 2: To develop models of T cell-mediated autoimmunity
Aim 3: To establish new iPSC lines and novel reporters of b cell stress and death
The specific aims of the UH3 phase are:
Aim 1: To develop isogenic models of autoimmune T1D
Aim 2: To identify determinants of islet infiltration and immune killing
Aim 3: To perform genetic studies of autoimmunity in T1D

## Key facts

- **NIH application ID:** 10467045
- **Project number:** 5UH3DK122644-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PAUL J GADUE
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,124,415
- **Award type:** 5
- **Project period:** 2019-08-02 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467045

## Citation

> US National Institutes of Health, RePORTER application 10467045, Microphysiological systems for modeling autoimmunity in type 1 diabetes (5UH3DK122644-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467045. Licensed CC0.

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