# NFkB Signaling in Macrophages

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $385,000

## Abstract

ABSTRACT
Inflammatory signaling by macrophages in response to pathogens or tissue injury is the key determinant of the
pathology and pathogenesis of infectious and non-infectious disease. The transcription factor NFκB controls
the inflammatory gene expression programs, but it remains unclear how its regulation determines healthy or
disease-associated gene expression responses.
During the previous funding period, we have used a combined experimental / computational modeling
approach to gain a predictive understanding of how NFκB is activated in response to TLR signaling and that
multiple mechanisms converge to regulate NFκB. After developing a live cell microscopy tracking workflow we
discovered that contrary to previous notions NFκB dynamics are highly oscillatory. By generating a knockin
RelA-Venus mouse, we are able – for the first time – measure NFκB dynamics in primary cells revealing
oscillations as an intrinsic hallmark of NFκB in healthy macrophages.
Based on preliminary studies, we propose to test the hypothesis that NFκB oscillations are critical for healthy
macrophage functions as they preserve their epigenetic chromatin state. Non-oscillatory NFκB is more likely
to alter the macrophage-characteristic chromatin state and lead to altered, disease-associated gene
expression. Further, while oscillations are pervasive, their duration is modulated by different stimuli, allowing
for differential, stimulus-specific gene expression programs.
Together, the proposed studies will substantially contribute to our understanding of how NFκB dynamic control
determines physiological and pathological gene expression programs.

## Key facts

- **NIH application ID:** 10054972
- **Project number:** 5R01AI127864-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Alexander Hoffmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2016-11-17 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054972

## Citation

> US National Institutes of Health, RePORTER application 10054972, NFkB Signaling in Macrophages (5R01AI127864-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054972. Licensed CC0.

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