# PPAR-delta as a Novel Therapeutic Target in Asthma

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $391,250

## Abstract

PROJECT SUMMARY
Asthma affects >300 million people, with high morbidity and healthcare costs. Improved therapies are needed,
because current therapies have adverse side effects and are ineffective in many patients. Asthma
pathophysiology involves complex regulatory mechanisms in many different cell types, still little-understood at
many levels. This research will test the role of a novel regulatory target in asthma, the orphan nuclear hormone
receptor peroxisome proliferator-activated receptor δ (PPARδ). Based on preliminary findings that PPARδ acts
within the lung to modulate asthma severity, we will determine if its dysregulation contributes to asthma, test
feasibility of its therapeutic targeting, and elucidate key mechanisms. Airway epithelial cells (AECs) are
important as both mediators and targets of asthma-related inflammation. Preliminary data suggest that PPARδ
is downregulated in AECs of asthma patients and lungs of mice with allergic airway disease (AAD), and that
globally downregulating PPARδ exacerbates AAD, whereas increasing PPARδ activity alleviates it. Our overall
goal is to elucidate the role of PPARδ in regulating asthma severity and the mechanisms involved. The aims
are: 1) to determine the mechanisms underlying induction of PPARδ ubiquitination and degradation by asthma-
related cytokines and whether the resulting PPARδ deficiency exacerbates AAD pathogenesis and severity,
comparing responses of wild-type AAD-bearing mice with those of novel strains having global or AEC-specific
PPARδ deficiency; 2) to test whether treatment with novel PPARδ agonists blocks effects of asthma-related
cytokines and agonist-induced or constitutive PPARδ activation ameliorates asthma severity specifically via
AECs. These studies will exploit our novel resources including PPARδ KO mice lacking the fetal mortality that
has hampered previous studies, a novel mouse strain expressing constitutively active PPARδ specifically in
AECs, and PPARδ agonists we developed that are uniquely suited to administration by inhalation, preferred for
asthma treatment. Taken together, our results will significantly advance understanding of PPARδ roles in lung
biology and disease, and identify a new target for improved asthma therapy.

## Key facts

- **NIH application ID:** 9944440
- **Project number:** 5R01AI125338-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** RAJU C REDDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2016-06-01 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944440

## Citation

> US National Institutes of Health, RePORTER application 9944440, PPAR-delta as a Novel Therapeutic Target in Asthma (5R01AI125338-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944440. Licensed CC0.

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