# Consequences and significance of TAK1 inhibition in macrophages

> **NIH NIH F31** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2022 · $13,718

## Abstract

Macrophages are essential cells for tissue maintenance and mediating inflammation, and they
reside ubiquitously throughout the body. Macrophages are primary phagocytic cells that engulf and
destroy pathogens, parasites and any unwanted material. However, some pathogens actively invade
macrophages to subvert and thwart macrophage defense. The pathogen-derived mechanisms to
evade macrophage defense include disrupting the immune response. Mitogen-activated protein
kinase kinase kinase 7 (MAP3K7), also known as TAK1, is a key intermediate molecule of the
intracellular inflammatory signaling pathways, and is, therefore, one of the major targets of immune
disruption by pathogens. It has been known that disruption of TAK1 not only blocks inflammatory
signaling but also triggers activation of two types of cell death pathways, i.e. apoptosis and
necroptosis. However, the biological significance of TAK1 inhibition-induced cell death pathways has
been obscure. I found that inhibition of TAK1 activates these pathways and limits intracellular
bacterial growth in macrophages. Most notably, it is associated with increases of mitochondrial
reactive oxygen species (ROS). I hypothesize that mitochondrial ROS are a mediator of the
macrophage defense against bacterial inhibition of TAK1. I aim to; i) characterize the effects of
mitochondrial ROS induced by TAK1 inhibition on bacterial growth and mitochondrial homeostasis; ii)
elucidate the mechanisms through which TAK1 regulates mitochondrial ROS. Outcomes of this
project would yield novel understanding of TAK1 function, macrophage biology and host defense
mechanisms.

## Key facts

- **NIH application ID:** 10434747
- **Project number:** 5F31GM135975-03
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Wilfred Javier Lopez-Perez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $13,718
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434747

## Citation

> US National Institutes of Health, RePORTER application 10434747, Consequences and significance of TAK1 inhibition in macrophages (5F31GM135975-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434747. Licensed CC0.

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