# Functional Characterization of Prostaglandin D2 in Chronic Spontaneous Urticaria

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2021 · $196,186

## Abstract

ABSTRACT
This K23 Mentored Career Development Award will provide Eric T. Oliver, MD, with the skills and training
necessary for a career as an independent investigator equipped to advance our understanding of allergic skin
disease. Urticaria affects 25% of individuals during their lifetime and is the cardinal symptom of many allergic
reactions including anaphylaxis. Despite this, little is known of the pathogenesis of chronic forms of urticaria
that affect ~1% of the population. Nearly all of these individuals lack an identifiable cause for their symptoms
and are thus classified as having chronic spontaneous urticaria (CSU). Treatment is aimed at reducing pruritus
and lesion severity, yet a substantial portion of CSU patients are refractory to current FDA-approved therapies.
The lack of a clear pathogenesis has prevented the development of safe and effective therapies for refractory
CSU. Dr. Oliver proposes that prostaglandin D2 (PGD2) is a key mediator in CSU skin lesions and promotes
the urticarial response by activating leukocytes and keratinocytes. Biopsies of CSU skin lesions reveal
evidence of mast cell degranulation, keratinocyte activation, and a leukocyte-predominant inflammatory
infiltrate. Upon activation, mast cells synthesize and release copious quantities of PGD2, which serves as the
primary ligand for the CRTh2 receptor. Through CRTh2, PGD2 and its metabolites mediate a number of
activating effects on leukocytes including chemotaxis and Th2 cytokine production. Dr. Oliver discovered that
blood leukocytes from CSU patients display decreases in surface CRTh2 expression and function, consistent
with in vivo PGD2 exposure. Additionally, he found that treatment with an oral CRTh2 antagonist increases
CRTh2 expression, increases circulating eosinophils, and decreases patient-reported itch in CSU patients.
Building on Dr. Oliver's previous work, this proposal will establish the novel functional effects of PGD2 on
leukocyte activation, define the production of PGD2 and its metabolites in CSU skin lesions, and determine the
activating effects of PGD2 on human skin explants. This career development award will provide Dr. Oliver with
the support necessary to establish himself as an independent clinician scientist focused on the pathogenesis
and treatment of CSU. He has assembled a mentoring team led by Dr. Sarbjit Saini, an internationally-
recognized expert in chronic urticaria. The other members of his mentoring team (Drs. Franklin Adkinson, Luis
Garza, and Donald MacGlashan) all have track records of mentoring young investigators and conducting NIH-
funded studies. His career development plan will bolster his knowledge of basic immunology and clinical
investigation, while he also develops proficiency in dermatologic research procedures and techniques. This
project will be conducted at the Johns Hopkins Asthma and Allergy Center, a national referral center for CSU.
He will also utilize his collaborations with the NIH to enrich his research ...

## Key facts

- **NIH application ID:** 10201476
- **Project number:** 5K23AI139394-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Eric T Oliver
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,186
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201476

## Citation

> US National Institutes of Health, RePORTER application 10201476, Functional Characterization of Prostaglandin D2 in Chronic Spontaneous Urticaria (5K23AI139394-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201476. Licensed CC0.

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