# TAK1 signaling pathways

> **NIH NIH R35** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2022 · $370,462

## Abstract

Abstract
 Innate immune signaling pathways are activated in response to exposure to microorganisms, and
generally are effective in preventing pathogen invasion through inducing inflammation and host cell death.
However, its aberrant activation is known to be causally associated with many inflammatory diseases e.g.
cancers and neurodegeneration, as it could cause tissue damage through inflammation and cell death. The
innate immune signaling pathways are highly complex as they have evolved in response to evolving
microorganisms trying to evade the host immunity. Thus, the regulatory mechanisms of innate immunity
particularly their signaling connections/networks are incompletely understood. Understanding the complexities
of the innate immune signaling network is highly anticipated to impact our ability to develop strategies to fight
pathogen infection and to treat inflammatory diseases. We have been studying mitogen-activated protein
kinase kinase kinase 7 (MAP3K7), known as TAK1, since its discovery. Initially we identified that TAK1
mediates transcriptional activation of inflammatory responses by activating both MAPK cascades and NF-κB
pathways. More recently, through our characterization of numerous tissue-specific Tak1-deficient mouse
models we have revealed that TAK1 also participates in cell death. However, there remain unanswered
fundamental questions; why and how do the inflammatory and cell death pathways converge through TAK1?
The R35 stable funding mechanism is highly suitable for this challenging project. We have all the materials,
e.g. genetically engineered mouse models and pharmacological modulators, and experience for answering the
above central question. For the next 5 years, we propose to determine the molecular mechanisms of how
inflammatory and cell death pathways are connected at TAK1 and of how aberrant activation of TAK1 leads to
inflammatory diseases.

## Key facts

- **NIH application ID:** 10318180
- **Project number:** 5R35GM139601-02
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Jun Ninomiya-Tsuji
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,462
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318180

## Citation

> US National Institutes of Health, RePORTER application 10318180, TAK1 signaling pathways (5R35GM139601-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318180. Licensed CC0.

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