# STAT3 variants as a rheostat of immune tolerance

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $1,765,357

## Abstract

Project Summary/Abstract (Overall)
Dysregulation of the immune system can have severe consequences on health and wellbeing. Although this is
often a complex process, recent progress in human genetics has allowed for the identification of single gene
variants that are strongly associated with immune dysregulation. Here, in this program project grant three
complementary teams will be working together to further unravel how heterozygous mutations that lead to gain
of function activity (GOF) of the STAT3 gene can strongly predispose to disease. Moreover, through our efforts
we hope to discover potential new methods to reverse this defect. This program project will have three highly
collaborative and interactive projects headed by Drs. Megan Cooper, Mark Anderson, and Alex Marson
along with two scientific cores. The major themes of the grant are:
1. More refined analysis of the immune cell dysfunction in STAT3 GOF patients
2. Using state of the art animal modeling approaches to interrogate STAT3 GOF mutations in triggering
 skin inflammation and type 1 diabetes
3. Utilizing state of the art CRISPR/Cas9 methods to interrogate STAT3 GOF dysfunction
4. Modeling methods to genetically repair defective STAT3 in human cells
The long-term objectives of this work are to improve our understanding of how STAT3 can serve as a tunable
rheostat to control immune tolerance and immune dysregulation. Results of these studies will help further
refine our understanding of autoimmunity inflammation and help improve methods for its treatment and
diagnosis.

## Key facts

- **NIH application ID:** 10763404
- **Project number:** 5P01AI155393-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Mark S Anderson
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,765,357
- **Award type:** 5
- **Project period:** 2022-02-17 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763404

## Citation

> US National Institutes of Health, RePORTER application 10763404, STAT3 variants as a rheostat of immune tolerance (5P01AI155393-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10763404. Licensed CC0.

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