# An Alternative Pathobiology underlying Severe Asthma

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $163,188

## Abstract

Project Abstract
This application is for a Mentored Patient-Oriented Research Career Development Award entitled “An
Alternative Pathobiology underlying Severe Asthma.” I am an Assistant Professor of Medicine at the
University of Pittsburgh seeking additional training in benchtop murine research techniques and bioinformatics
and ‘omics analysis to transition from benchtop to translational asthma research. The focus of my research is
on the role of Type-1 (T1) inflammation in asthma and how this pathway may contribute to disease severity.
While great strides have been made in understanding and treating traditionally described Type-2 (T2)
inflammation in asthma with novel biologic therapies, nearly 50% of asthma patients lack evidence of this
pathway, and even some with T2 inflammation fail to respond well to T2 therapies. A better understanding of
other inflammatory pathways in asthma and how they contribute to disease is essential to identifying novel
therapeutics for these patients. My preliminary data have demonstrated the presence of T1 inflammation marked
by increased expression of IFN-γ, the chemokines CXCL10 and CCL5 as well as T1 expressing tissue resident
memory T-cells (T1 TRM) in ~30% of asthma patients. These patients tend to have more severe asthma, greater
exacerbations and higher use of systemic corticosteroids. However, the reliance on bronchoscopy for samples
has limited our ability to study the clinical effects of this pathway over time. Furthermore, our understanding of
the effects of T1 inflammation on the airways in asthma and the role of T1 TRM cells in maintaining/driving this
phenotype are unknown. This study aims to improve our understanding of asthmatic T1 inflammation in three
ways: (1) Utilize our T1 dominant murine severe asthma model to assess TRM establishment and reactivation in
T1High asthma. (2) To assess the importance of maraviroc (a CCR5 inhibitor) in effecting T1 specific changes on
the airway epithelium and mast cell prevalence. (3) The multicenter Severe Asthma Research Program provides
clinical data in a large number of asthma subjects with paired sputum samples that will allow us to measure T1
inflammatory markers, assess their correlation with clinical outcomes and identify future biomarkers to better
identify T1High asthmatics for future trials. This project will provide unique insight into a novel and poorly
understood pathway in asthma with the potential to yield exciting new treatment options for a highly prevalent
and severe disease. This study will also provide the opportunity for me to acquire skills in bioinformatics and
large ‘omics dataset analysis that will foster my development as a translational physician scientist in severe
asthma in addition to advancing my murine model skillset. The work will be carried out at the University of
Pittsburgh in the division of Pulmonary, Allergy and Critical Care which has a strong track record of developing
physician scientists and boasts a highly developed i...

## Key facts

- **NIH application ID:** 10896314
- **Project number:** 5K08HL164887-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Marc Gauthier
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,188
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896314

## Citation

> US National Institutes of Health, RePORTER application 10896314, An Alternative Pathobiology underlying Severe Asthma (5K08HL164887-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896314. Licensed CC0.

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