# Coordinated dynamic regulation and function of IRF transcription factors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $390,000

## Abstract

Project Summary/Abstract
Innate immune signaling by macrophages is critical as the first response to pathogen exposure. Three
Interferon-regulatory factors (IRFs) are the critical regulators of the innate immune response (namely IRF3,
ISGF3, and IRF7), and they respond to pathogen exposure coordinately and interdependently. How these
IRFs function as a regulatory system, and what their specific roles are in regulating the extensive gene
expression programs comprising hundreds of genes, has remained unclear, as previous assays lacked
resolution to quantitate IRF dynamics at single cell resolution, and interdependencies between these factors
could not be delineated by prevailing models.
Thus the scientific premise of the proposed studies is that utilizing cutting-edge quantitative single cell and
genome-wide measurements will allow us develop a quantitative mathematical model that delineates
respective functions of IRF3, ISGF3, IRF7. We will address this goal with the following Aims:
In Aim 1, we will elucidate the mechanism that are able to produce the complex dynamic control of the primary
response factor IRF3 that we reveal in our preliminary studies.
In Aim 2, we will investigate the functional consequence of differential, pathogen-specific IRF3 dynamics on
chromatin control and target gene expression.
In Aim 3, we will develop a predictive signaling model of the dose response and dynamic control of ISGF3
activated via autocrine and paracrine type I interferon secretion, and characterize how it contributes to innate
immune gene expression in both infected and in bystander cells.
In Aim 4, we will examine the regulatory control of IRF7 and test the hypothesis that it plays a key role in
determining innate immune responses in previously interferon-`warned' cells, thus mediating a form of innate
immune memory.

## Key facts

- **NIH application ID:** 9932886
- **Project number:** 5R01AI132835-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Alexander Hoffmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2017-06-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932886

## Citation

> US National Institutes of Health, RePORTER application 9932886, Coordinated dynamic regulation and function of IRF transcription factors (5R01AI132835-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932886. Licensed CC0.

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