# Molecular mechanism of NLRP3 inflammasome activation

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $380,140

## Abstract

Project Summary
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) is a critical component of the
innate immune system that forms the NLRP3 inflammasome, an intracellular molecular platform
that drives caspase-1 activation and the secretion of biologically active IL-1β and IL-18. In addition
to its protective role in innate immunity, aberrant activation of the NLRP3 inflammasome
contributes to the pathogenesis of several inherited and acquired inflammatory disorders, such
as Cryopyrin-associated autoinflammatory syndrome, gout, Crohn's disease, Alzheimer's
disease, diabetes and atherosclerosis. Despite extensive investigation, the molecular mechanism
leading to NLRP3 inflammasome activation remains elusive. Recently, the protein kinase Nek7
has been found to mediate NLRP3 inflammasome activation independently of its kinase activity.
However, it is unknown how Nek7 is mechanistically linked to NLRP3 inflammasome activation.
Our recent studies implicate a critical role for Nek7 phosphorylation in NLRP3 inflammasome
activation. In this application we aim to elucidate the molecular mechanism of Nek7-mediated
NLRP3 inflammasome activation and determine the role of a novel regulator in this pathway. Our
results are expected to provide new mechanistic insights into NLRP3 inflammasome activation
and might guide the development of novel therapeutic strategies for treating NLRP3-driven
inflammatory diseases.

## Key facts

- **NIH application ID:** 10048426
- **Project number:** 1R01AI148544-01A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Yuan He
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,140
- **Award type:** 1
- **Project period:** 2020-05-04 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048426

## Citation

> US National Institutes of Health, RePORTER application 10048426, Molecular mechanism of NLRP3 inflammasome activation (1R01AI148544-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10048426. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*