# Mechanisms and Targeted Control of Pancreatic B-Cell Antioxidant Response

> **NIH NIH F31** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $31,022

## Abstract

PROJECT SUMMARY
Type 1 Diabetes (T1D) is an autoimmune disease caused by progressive destruction of the insulin producing β-
cells. The loss of immune tolerance is a result of predisposing genes and environmental factors. However, the
exact trigger of autoimmune attack is currently not understood. During the development and progression of T1D,
β-cell oxidative stress is a key contributing factor to β-cell dysfunction and destruction. For many years it was
thought that β-cells were completely destroyed in individuals with T1D. Recently, this dogma has been
challenged by the observation of residual insulin positive β-cells in individuals with long-standing T1D. Similarly,
in the nonobese diabetic (NOD) mouse model for T1D, there is a subpopulation of β-cells that are able to
withstand prolonged immune attack. These data suggest there is a population of β-cells that are able to adapt
and survive during conditions of high stress. To build on these findings, the central goal of this proposal is to
define pathways to promote β-cell survival and protection against T1D. I hypothesize that rapid activation of the
antioxidant response reduces β-cell ROS to repress islet immunogenicity during T1D pathogenesis. I will test
this hypothesis through two specific aims. Experiments in aim 1, will investigate how β-cell selective loss of
NRF2 contributes to the development of autoimmune diabetes. In aim 2, I will identify the mechanism controlling
β-cell ROS mitigation in early T1D pathogenesis. Completion of these aims will determine the functional role and
mechanism of β-cell adaptive redox response in vivo. Importantly, this work will identify novel targets to prevent
β-cell destruction under diabetogenic conditions, and tools developed and tested as a part of this work can be
used in future studies to target therapeutics or imaging probes to the β-cells. These studies will also positively
impact my career. Both a comprehensive understanding of islet function in early diabetes pathogenesis and the
use of cutting-edge techniques will enable me to develop as a scientist and set me on a trajectory to make real
and lasting impacts in the field of diabetes research. This F31 award entails a 2-year training plan designed to
achieve 4 main objectives: 1) build a strong understanding of techniques and concepts in diabetes research, 2)
train in the generation and use of targeted nanoparticles and pharmacodynamics for diabetes research, 3) train
in oral and written presentation of research findings, including grant preparation, and 4) train in the use and
handling of mouse models for diabetes research. In addition, the applicant will benefit from the outstanding and
collaborative research environment provided by the Center for Diabetes and Metabolic Diseases at the Indiana
University School of Medicine. Her training will also benefit from a mentoring and advisory committee consisting
of a diverse team of carefully selected and established NIH funded investigators. In sum...

## Key facts

- **NIH application ID:** 10465868
- **Project number:** 1F31DK130606-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Alissa N Novak
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,022
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465868

## Citation

> US National Institutes of Health, RePORTER application 10465868, Mechanisms and Targeted Control of Pancreatic B-Cell Antioxidant Response (1F31DK130606-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465868. Licensed CC0.

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