# Genetic control of mature beta cell function and identity

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $366,806

## Abstract

Project Summary/Abstract
Functionally mature beta cells are essential to glucose homeostasis and their loss or dysfunction underlies all
types of diabetes mellitus. In recent years, it has become clear that not all beta cells are permanently lost in
either type of diabetes. Instead, chronically stressed beta cells lose their functionally mature phenotype and
shift to a dysfunctional state in a process called de-differentiation. Preventing or reversing beta cell de-
differentiation represents a promising approach to restoring functionally mature beta cell mass in diabetics. We
have recently identified five novel genetic regulatory networks that we hypothesize to be important for regulat-
ing mature beta cell function and identity. The overarching goal of this proposal is to establish the above five
regulatory networks as novel genetic and pharmacological switches for controlling beta cell function and identi-
ty. In Aim 1, we will map in detail each of the networks by determining direct and indirect regulated nodes for
each regulator. We will further identify the networks' cellular function and find upstream signaling pathways
predicted to affect the networks' behavior in both human and mouse beta cells, and their points of perturbation
during beta cell de-differentiation. In Aim 2, we will test the causality of the five predicted regulators on beta cell
function and identity in vitro in primary mouse and human islets, and in vivo, using genetic mouse models
where available. We will further test the effect of genetic intervention points in the networks to lock in place ma-
ture beta cell identity under the different diabetogenic stresses.

## Key facts

- **NIH application ID:** 10746113
- **Project number:** 5R01DK131438-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Barak Blum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,806
- **Award type:** 5
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746113

## Citation

> US National Institutes of Health, RePORTER application 10746113, Genetic control of mature beta cell function and identity (5R01DK131438-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10746113. Licensed CC0.

---

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