# Project 1: Dynamic Host Responses During Resolution of HAP

> **NIH NIH U19** · NORTHWESTERN UNIVERSITY · 2022 · $511,844

## Abstract

Project Summary Project 1: Dynamic Host Responses During Resolution of HAP
 
Hospital-acquired pneumonia (HAP) is one of the leading causes of death from nosocomial infections, with high
rates of associated mortality. HAP due to Pseudomonas aeruginosa and Acinetobacter spp. is substantially more
difficult to treat than other pathogens, with clinical failure rates as high as 50%. These rates persist despite
optimization of antibiotic regimens, suggesting factors beyond antibiotic resistance contribute. In this Project, we
will examine the host response to pneumonia. We hypothesize that persistent inflammation in the alveolus after
appropriate antibiotic treatment contributes to clinical failure in patients with P. aeruginosa or Acinetobacter spp.
pneumonia. We will test this hypothesis in three interrelated Specific Aims. Aim 1. To determine whether
pathogen-associated changes in the transcriptomic signatures of alveolar macrophages and lymphocyte subsets
over time predict outcome of severe pneumonia. Aim 2. To prospectively validate predictive host responses
identified using an ecosystem-based modeling approach in a separate cohort of patients with severe pneumonia.
Aim 3. To determine whether validated host responses predictive of clinical outcome are related to pneumonia
endpoints in murine models. We will combine clinical data from the Electronic Health Record and integrate these
clinical data with transcriptomic and epigenomic data obtained from flow sorted alveolar macrophages and Treg
cells isolated from serial samples of NBBAL over the course of the patient's illness. Through the development of
these predictive tools, the SCRIPT Systems Biology Center offers the potential to discover novel pathways that
drive pneumonia pathobiology for therapeutic targeting, and the ability to revise understanding of pneumonia as
a complex interaction between the host, pathogen, and microbiome.

## Key facts

- **NIH application ID:** 10326814
- **Project number:** 5U19AI135964-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** RICHARD G WUNDERINK
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $511,844
- **Award type:** 5
- **Project period:** 2018-01-17 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326814

## Citation

> US National Institutes of Health, RePORTER application 10326814, Project 1: Dynamic Host Responses During Resolution of HAP (5U19AI135964-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10326814. Licensed CC0.

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