# Mediators of chronicity in autoimmune endocrinopathies.

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $315,515

## Abstract

PROJECT SUMMARY / ABSTRACT (PRINCIPAL PROJECT)
PRINCIPAL PROJECT: Molecular and cellular mechanisms of chronicity in autoimmune
endocrinopathies
Autoimmune endocrinopathies are chronic diseases, in which patients suffer permanent tissue damage and
require lifelong hormone replacement. In Type 1 Diabetes (T1D), for example, autoimmune destruction of insulin-
producing beta cells does not remit, and patients require long-term exogenous insulin administration. Exogenous
insulin regimens do not entirely mimic the exquisite control of physiologic hormone secretion, however, and often
leaves patients with sub-optimal glucose control. Unlike most other autoimmune conditions, autoimmune
endocrinopathies are not currently treated with immunotherapies first-line, despite overwhelming evidence for
their autoimmune cause. Here, we will test the hypothesis that chronicity in human autoimmune endocrinopathies
is driven by epigenetic and molecular mechanisms that promote progenitor self-renewal and conversion to
pathogenic effectors. In Aim 1, we will determine the role of the epigenetic regulator UTX in promoting progenitor
to effector conversion. Our preliminary data in mouse models identified a role for UTX in mouse CD8+ T cell
progenitor to effector conversion, and we will determine whether parallel pathways exist to regulate human CD8+
T cell progenitor to effector conversion. In Aim 2, we will identify epigenetic and molecular factors important in
stem-like progenitor self-renewal. Identifying immune mechanisms that underlie chronicity in autoimmune
endocrinopathies will lead to new therapeutic approaches for terminating the long-term autoimmune response.
In both Aims, we will test the effects of small molecule inhibitors and biologic antagonists that target pathways
important in autoimmune chronicity in order to enhance the translational potential of our studies to the clinical
realm.

## Key facts

- **NIH application ID:** 10845210
- **Project number:** 1U19AI181729-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** MANISH J BUTTE
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $315,515
- **Award type:** 1
- **Project period:** 2024-09-10 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845210

## Citation

> US National Institutes of Health, RePORTER application 10845210, Mediators of chronicity in autoimmune endocrinopathies. (1U19AI181729-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10845210. Licensed CC0.

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