# Project 1: Functional consequences of STAT3 GOF on immune cell signaling

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $393,750

## Abstract

Project Summary/Abstract
Primary immune dysregulation syndromes are group of rare monogenic disorders affecting immune tolerance
and leading to early-onset immunodeficiency, autoimmunity, and risk of malignancy. STAT3 gain-of-function
(GOF) syndrome was recently described as a primary immune dysregulation syndrome causing early-onset
polyautoimmunity and lymphoproliferation. While we have a good understanding of the genetic basis of STAT3
GOF syndrome, the underlying mechanisms of immune dysregulation and relevant cell types that should be
targeted for therapy of disease are less clear. We hypothesize that dysregulation of T cells in STAT3 GOF leads
to disease and that this is a relevant cell type that can be targeted for therapy. We will investigate this hypothesis
in collaboration with Drs. Anderson and Marson by deeply interrogating the immune response in patients with
STAT3 GOF and using new mouse models of disease. The long-term goals of this project are to understand how
immune tolerance is lost with STAT3 GOF to gain a better understanding of mechanisms of immune tolerance
in humans and provide personalized and precision therapy for the treatment of this and other rare immunologic
diseases of childhood. In this project we will investigate mechanisms of immune dysregulation by: 1) identifying
the variants in STAT3 that alter function and interrogating immune cells signals that are altered by STAT3 GOF
using primary patient samples and cells from murine models of STAT3 GOF using sequencing techniques; 2)
Identifying novel autoantibodies from patient samples using a broad-based approach; and 3) Investigating a
model of skin inflammation in STAT3 GOF mice to determine relevant cell types in a disease model and
interrogate the response to JAK inhibition.

## Key facts

- **NIH application ID:** 10328101
- **Project number:** 1P01AI155393-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MEGAN Anne COOPER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,750
- **Award type:** 1
- **Project period:** 2022-02-17 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328101

## Citation

> US National Institutes of Health, RePORTER application 10328101, Project 1: Functional consequences of STAT3 GOF on immune cell signaling (1P01AI155393-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10328101. Licensed CC0.

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