# Eicosanoid Networks in Aspirin Hypersensitivity

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $656,461

## Abstract

Summary/Abstract
This application for renewed support continues its focus on the mechanisms responsible for
aspirin sensitivity, a defining feature of aspirin exacerbated respiratory disease (AERD). AERD
is a debilitating clinical syndrome characterized by severe sinonasal and bronchial inflammation
resulting in chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma, respectively. Few
therapeutic options exist, and none have disease modifying properties. Our proposal focuses on
a unique, platelet-driven mechanism through which endogenous cysteinyl leukotrienes (cysLTs),
specifically the parent cysLT LTC4, elicits biased signaling through the type 2 cysLT receptor
(CysLT2R) on platelets and other cell types to drive immunopathology through IL-33. The central
hypotheses are that LTC4 signals at CysLT2R to promote respiratory type 2 inflammation by
inducing the expression and release of interleukin 33 (IL-33) by both direct and indirect
mechanisms. A corollary hypothesis is that AERD involves a significant pathogenetic
contribution from an autocrine LTC4/CysLT2R-mediated platelet activation pathway that provides
IL-33 and other mediators that contribute to respiratory tract T2I and drive aspirin sensitivity. We
use a complementary approach with molecular tools, a unique set of transgenic mice, and
tissues and cells from carefully phenotyped human subjects to test the core hypotheses and
validate the biology across species. The studies should reveal new potential strategies for
therapeutic development that are based on a novel underlying mechanism,

## Key facts

- **NIH application ID:** 10756094
- **Project number:** 5R01AI136041-11
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joshua A Boyce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $656,461
- **Award type:** 5
- **Project period:** 2017-12-04 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756094

## Citation

> US National Institutes of Health, RePORTER application 10756094, Eicosanoid Networks in Aspirin Hypersensitivity (5R01AI136041-11). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10756094. Licensed CC0.

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