# The Role of Alveolar Mononuclear Phagocytes in Acute Respiratory Distress Syndrome

> **NIH NIH K23** · UNIVERSITY OF WASHINGTON · 2020 · $190,188

## Abstract

Project Summary/Abstract
Acute respiratory distress syndrome (ARDS) has an associated 28-day mortality as high as 33%, however
there are no effective pharmacologic interventions specifically targeted at ARDS pathogenesis that improve
outcomes for these patients. Alveolar macrophages (AMs) are the most abundant leukocyte in the
homeostatic human lung. They are presumed to be a key regulator of both the inflammatory and reparative
processes of ARDS given their phenotypic plasticity and functional heterogeneity. This phenotypic plasticity
endows AMs with many potential reprogramming targets which might be used as treatment strategies for
ARDS. Animal studies have found multiple AM subtypes that are present in acute lung injury, however
information regarding human AM subtypes in health and ARDS is very limited. Dr. Eric Morrell has developed
a research program that has found different AM phenotypic and transcriptional subtypes are associated with
ARDS and ARDS-related outcomes, respectively.
Dr. Morrell’s overall goal is to characterize the functional and transcriptional differences between AM subtypes
in ARDS and to determine whether AM subtypes influence ARDS severity. He will specifically work to achieve
this goal through the following 3 Aims: 1) Test for associations between AM subtypes and ARDS severity using
mass cytometry (CyTOF); 2) Determine whether different AM subtypes differentially secrete inflammatory
mediators, and assess if soluble alveolar inflammatory signals mediate associations between AM subtypes and
ARDS severity; and 3) Characterize the transcriptional programs of AM subtypes in ARDS using single-cell
RNA sequencing.
The Career Development Plan for this grant proposal is designed to provide training for Dr. Morrell in human
cohort management, epidemiology, “omics” analytics, and statistical methods. These new skills will augment
his basic science background and facilitate his overall goal of developing into an independent translational
physician-scientist who can obtain and integrate complex biologic data into epidemiologic and statistical
models to answer clinically-oriented research questions. Armed with the data generated by this project as well
as the training outlined in the Career Development Plan, Dr. Morrell will have the infrastructure and skills
necessary to submit a competitive R01 grant proposal at the end of his proposed K23 funding period. Future
projects that could build upon this grant proposal include using single-cell assays to predictively enrich for
ARDS subpopulations that might respond to therapies, studying the relationship between reparative AM
subtypes and ARDS clinical outcomes using longitudinally-collected patient samples, and collaborating with
other ARDS investigators to examine specific targets that are identified through the project’s specific Aims.

## Key facts

- **NIH application ID:** 10002267
- **Project number:** 5K23HL144916-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Eric Douglas Morrell
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,188
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002267

## Citation

> US National Institutes of Health, RePORTER application 10002267, The Role of Alveolar Mononuclear Phagocytes in Acute Respiratory Distress Syndrome (5K23HL144916-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10002267. Licensed CC0.

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