# Uncovering the Interplay Among Pancreatic Tissue Types, Inflammation, and Genotypes in Type 1 Diabetes

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $279,713

## Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease caused by the destruction of pancreatic beta cells in
the islets of Langerhans. Genome-wide associated studies (GWAS) have implicated several dozen genes in
T1D, but few are expressed by or unique to beta cells. We hypothesize that a combination of genetic and
environmental factors contributes to immune and exocrine-endocrine crosstalk leading to the loss of beta cell
mass. In this multidisciplinary study, we will investigate the relationship between pancreatic tissue types,
inflammation, and genotypes to uncover new insights into the initiating events of T1D. We will generate
immune cells and pancreatic exocrine and endocrine organoids with induced pluripotent stem (iPS) cells
derived from patients with T1D to produce a reproducible platform for our proposed study. Specific Aim 1 will
delineate transcriptional and chromatin accessibility changes of pancreatic exocrine and endocrine tissues
under inflammation with T1D-risk variants to identify T1D cell type-specific regulatory programs. Specific Aim 2
will determine changes in pancreatic exocrine and endocrine function on immune responses with T1D-risk
variants. Specific Aim 3 will establish a microcontact printing co-culture system of pancreatic exocrine and
endocrine tissue to investigate tissue interactions in the context of stress with T1D-risk variants. The multi-
tissue assemblies will be evaluated with spatial transcriptomics to identify the relationship between tissue
cross-talk and transcriptional identity. Successful completion of this study will provide a better understanding of
the relationship between pancreatic exocrine and endocrine cells in the context of defined genotypes and
environmental factors in the development of T1D. The data and novel co-culture platform generated in this
study will benefit the T1D community.

## Key facts

- **NIH application ID:** 10802854
- **Project number:** 1R01DK138469-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jeffrey Robert Millman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $279,713
- **Award type:** 1
- **Project period:** 2024-01-02 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802854

## Citation

> US National Institutes of Health, RePORTER application 10802854, Uncovering the Interplay Among Pancreatic Tissue Types, Inflammation, and Genotypes in Type 1 Diabetes (1R01DK138469-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10802854. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*