# Modulating intrinsic beta cell stress to block diabetes pathogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $668,886

## Abstract

Project Summary/Abstract
Diabetes and its complications affect an ever-growing part of the global population. Recent studies point to
beta cell defects as a common denominator in Type 1 and Type 2 diabetes. Here, we propose to interrogate
the contribution of distinct coping mechanisms present in beta cells that serve to protect against physiological
stress, but whose dysfunction can result in deterioration or destruction of beta cells under conditions of
extended or unresolved stress. We focus on the connections between ER stress resulting in the unfolded
protein response (UPR) and loss of beta cell identity caused by a novel regulator of beta cell identity. We
propose to determine how these pathways interact and how they inform beta cell function. The proposed work
is exclusively performed in human beta cells and takes advantage of our ability to generate and CRISPR-
modify functional insulin producing cells from human stem cell populations. The overall goal of our proposed
studies is to define the mechanisms resulting in beta cell dysfunction and subsequent diabetes, with a clear
focus on identifying those signaling nodes that can be exploited for therapeutic intervention. We have
assembled a team of leading experts on these specific cellular outcomes and have developed pharmacological
and genetic tools to address how halting stress response in beta cells can alter the course of the disease. We
pose that directly targeting stress response pathways in beta cells is an innovative and novel approach to
diabetes treatment and prevention that also has implications for other degenerative diseases.

## Key facts

- **NIH application ID:** 10647729
- **Project number:** 5R01DK129935-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Matthias Hebrok
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $668,886
- **Award type:** 5
- **Project period:** 2021-08-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10647729

## Citation

> US National Institutes of Health, RePORTER application 10647729, Modulating intrinsic beta cell stress to block diabetes pathogenesis (5R01DK129935-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10647729. Licensed CC0.

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