# Endothelial S1PR1 promotes lung repair in post-viral ARDS

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $161,240

## Abstract

Viral respiratory infections, such as influenza and SARS-CoV2, frequently lead to acute
respiratory distress syndrome (ARDS), a condition with a mortality up to 46%. Endothelial injury,
dysfunction and the resultant vascular hyperpermeability contribute to the severity of ARDS,
persistence of lung injury, and dysregulated repair with the development of fibrosis. While
sphingosine-1-phosphate receptor 1 (S1PR1) is a key protective signaling axis on endothelial
cells, the role of S1PR1 signaling in the resolution of lung injury in post-viral ARDS has not been
well explored.
The objective of this application is to define endothelial S1PR1-dependant pathways which
promote the re-alveolarization of the post-viral lung needed to prevent morbid fibrotic outcomes.
We hypothesize that endothelial S1PR1 signaling promotes productive lung repair after viral
infection via BMP2 mediated support of the epithelial niche. These preliminary findings a new
facet to the pleotropic benefits of EC S1PR1 beyond its established role in limiting vascular
hyperpermeability and highlight a need to comprehensively validate the therapeutic potential of
augmenting S1PR1 expression to limit post-viral pulmonary fibrosis. We will test this hypothesis
via two specific aims: 1) determine the mechanism of endothelial S1PR1 mediated epithelial
repair after viral-induced ARDS, and 2) determine how EC S1PR1 regulation can be
therapeutically augmented to attenuate post-viral fibrosis. The proposed research will reveal novel
links between EC S1PR1 and epithelial regeneration and differentiation after viral infection and
identify regulators of endothelial function which can be therapeutically targeted to attenuate post-
viral fibrosis.
Dr. Brazee’s long-term goal is to be an independent basic and translational investigator with a
research program aimed at understanding the contributions of the endothelium in supporting
productive lung repair pathways. The proposed K01 research aims utilize prior training in mouse
models of influenza virus infection, fibrotic lung disease, and fundamental molecular biology
techniques. In addition, the project will necessitate advanced training in vascular and epithelial
biology, G-protein coupled receptor (GPCR) signaling, and translational modeling of human
disease using human derived 3D organoids and precision cut lung slices. Successful completion
of these aims, together with continued professional development, will provide the proficiencies
necessary to establish a productive research program and an impactful career as an independent
R01-funded investigator.

## Key facts

- **NIH application ID:** 10948951
- **Project number:** 1K01HL174822-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Patricia Louise Brazee
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,240
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948951

## Citation

> US National Institutes of Health, RePORTER application 10948951, Endothelial S1PR1 promotes lung repair in post-viral ARDS (1K01HL174822-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10948951. Licensed CC0.

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