# Innate immune signaling and stress response

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $538,500

## Abstract

ABSTRACT 
 
Membraneless  compartments  play  a  vital  role  in  maintaining  cellular  and  organismal  homeostasis  by 
modulating  cell  survival  and  cell  death.  Stress  granules,  and  inflammasome-­induced  specks  are 
membraneless  compartments  that  provide  contrasting  cell  fate  choices  to  the  cells  –  survival  or  pyroptosis 
(programmed  cell  death)  during  physiological  or  virus  induced  cellular  stress.    NLRP3,  a  global  sensor  of 
pathogen–associated  molecular  patterns  (PAMPs)  and  danger–associated  molecular  patterns  (DAMPs), 
senses  cellular  perturbations  in  the  cytosol  to  trigger  the  assembly  of  a  large  caspase-­1-­activating  protein 
complex  termed  the  NLRP3  inflammasome.  Autoproteolytic  maturation  of  caspase-­1  due  to  NLRP3 
inflammasome  activation  leads  to  pyroptosis,  and  maturation  of  pro-­inflammatory  cytokines  interleukin  (IL)-­
1β  and  IL-­18. Despite  the  ability  of NLRP3 to  respond  to  diverse  cues  of  cellular  or  virus  induced  stress, 
mechanisms  controlling  the  cross-­talk  between  inflammasomes  and  stress  granules  remain  elusive.  In  our 
quest  to  study  this  cross-­talk,  we  have  identified  DDX3X,  a  stress  granule  component,  as  an  upstream 
regulator of NLRP3 inflammasome to canonical and viral triggers. In this R01 renewal, we propose to identify 
the  molecular  and  cellular  mechanisms  of  DDX3X-­mediated  NLPR3  inflammasome  activation  and  its 
modulation by stress signals during inflammation and viral infections. Understanding the cross-­talk between 
cellular  stress  response  molecules  and  innate  immune  signaling  will  lead  to  novel  therapeutic  targets  for 
inflammatory and infectious diseases.

## Key facts

- **NIH application ID:** 10770514
- **Project number:** 5R01AI124346-09
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Thirumala-Devi Kanneganti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,500
- **Award type:** 5
- **Project period:** 2016-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770514

## Citation

> US National Institutes of Health, RePORTER application 10770514, Innate immune signaling and stress response (5R01AI124346-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10770514. Licensed CC0.

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