# Optimizing EP receptor subtype targeting for asthma therapy

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $537,546

## Abstract

Project Summary
Multiple studies by our investigative team and others demonstrate that prostaglandin E2 (PGE2) regulates the
function of multiple cell types in the lung, including resident structural cells, nerves, and infiltrating blood cells.
Although PGE2 has been shown to mediate numerous anti-inflammatory effects, it has also been shown to
promote certain pro-inflammatory actions, as well as undesirable side effects, the most prominent being cough,
that have stalled efforts to exploit its clinical potential. The numerous and complex effects of PGE2 are due, in
large part, to the existence of 4 different EP receptor subtypes. Each of EP receptor subtypes (EP1, 2, 3, and
4) promotes different signaling and function when stimulated by PGE2, while being differentially expressed in
the numerous cell types in the lung. The goal of this project is to take advantage of recent advances in EP
receptor pharmacology and research capabilities, to identify the optimal EP receptor targeting strategy to treat
asthma. Our central hypothesis is that EP receptors mediate a complex array of functions in the lung and in
allergic lung inflammation, and selective targeting of EP subtypes can provide optimal therapy for asthma by
ameliorating lung inflammation, airway hyperresponsiveness (AHR), and airway remodeling, while avoiding
promotion of cough. We have assembled a multi-PI, international team capable of exhaustively characterizing
EP subtype function, and the utility of EP targeting for the purpose of asthma therapy. Three Aims will be
pursued that constitute a robust analysis of the cooperative (positive and negative) roles of EP receptors in
cell, tissue, and in vivo models. Aim 1 will employ rodent models of allergic lung inflammation and assess the
effect of multiple combinations of EP agonists and antagonists on lung inflammation, airway remodeling, and
airway hyperresponsiveness. Aim 2 will focus on EP receptor signaling and regulation of relevant human and
rodent cell (airway smooth muscle, airway epithelia, and mast cells) functions. Aim 3 will employ cell, tissue,
and in vivo models to detail EP receptor regulation of cough. Upon conclusion of these studies we will have
identified a novel therapeutic approach that has long been suspected but has eluded the research community
for decades.

## Key facts

- **NIH application ID:** 9855066
- **Project number:** 5R01HL136209-04
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Mark A Birrell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $537,546
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855066

## Citation

> US National Institutes of Health, RePORTER application 9855066, Optimizing EP receptor subtype targeting for asthma therapy (5R01HL136209-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9855066. Licensed CC0.

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