# Immunosuppression in Acute Lung Injury

> **NIH NIH P01** · OHIO STATE UNIVERSITY · 2022 · $2,334,002

## Abstract

Acute respiratory distress syndrome (ARDS) is most commonly due to severe
pneumonia or sepsis. Decades of intense study have focused on the initial inflammatory
phase of ARDS, and yet mortality rates for ARDS are still very high because newer
pharmocotherapies have not emerged. In this Program Project Grant competing renewal
application, we have assembled a team of world-class leaders with complementary
expertise to investigate a new pathophysiologic model that challenges the existing
concept that ARDS is solely a hyper-inflammatory disorder. In this model, we will
investigate a novel concept that in ARDS, immunosuppression is a signature
manifestation in a subset of patients secondary to unique, combinatorial pathways that
modulate epithelial and myeloid cell viability and innate immune function. We
hypothesize that immune suppression occurs via chromatin remodeling and ubiquitin-
degradative pathways (Project 1), through a set of distinct cell death pathways including
a new form of oxidation driven, non-apoptotic cell death termed ferroptosis (Project 2),
through a phenotypic shift from loss of crucial host-protective lymphocytes (CD8+, MAIT
cells) to immunosuppressive myeloid cells (Project 3), and oxidation-mediated
impairment of macrophage bacterial killing and phagocytosis (Project 4). To evaluate
this hypothesis, investigators will employ state-of-art molecular, cell, human-based
systems, and lipidomic tools. These approaches will be translated to complementary 2-
hit models of lung injury and immunosuppression and analysis in ARDS human subjects.
The Program will be supported by two highly interactive Cores with expertise in human
biorepository services and bioimaging. Execution of these studies will provide a
paradigm-changing conceptual model for ARDS pathogenesis that serves as a basis for
therapeutic intervention and providing a new and sustained field of scientific inquiry in
lung biology.

## Key facts

- **NIH application ID:** 10399554
- **Project number:** 5P01HL114453-09
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Rama K Mallampalli
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,334,002
- **Award type:** 5
- **Project period:** 2014-01-03 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399554

## Citation

> US National Institutes of Health, RePORTER application 10399554, Immunosuppression in Acute Lung Injury (5P01HL114453-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399554. Licensed CC0.

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