# Systems Biology Modeling of Severe Hospital-Acquired Pneumonia

> **NIH NIH U19** · NORTHWESTERN UNIVERSITY · 2024 · $400,789

## Abstract

PROJECT SUMMARY/ABSTRACT – Project 2
Mechanical ventilation has saved the lives of countless patients with respiratory failure but may lead to the
dreaded complication of ventilator-associated pneumonia (VAP), a form of hospital-acquired pneumonia (HAP).
HAP/VAP are associated with particularly high mortality rates despite the administration of appropriate and highly
potent antibiotics. Recent work suggests that the host inflammatory response, the specific pathogenic strain
causing the infection, and the pulmonary microbiome all contribute to the pathogenesis of HAP/VAP. However,
to our knowledge these three contributing factors have not been comprehensively examined together. To better
understand HAP/VAP, we established the Successful Clinical Response in Pneumonia Therapy (SCRIPT)
Systems Biology Center to enroll pneumonia patients, collect bronchoalveolar lavage samples from them, and
apply multi-omic approaches to these samples. We hypothesize that these approaches will identify specific host
response patterns, pathogen genetic biosignatures, and pulmonary microbiome consortia that define and predict
the clinical trajectory of patients with HAP/VAP and define the pathogenesis of these infections. To test this
hypothesis, we will perform the following aims: (1) Identify host response biosignatures, (2) features of bacterial
pathogens, and (3) patterns of pulmonary microbiome consortia that inform pathogenesis and are associated
with clinical improvement or deterioration in HAP/VAP. (4) Integrate host response, pathogen, and microbiome
features with clinical metadata to generate a comprehensive computational model that predicts clinical outcomes
and favorable/unfavorable transitions in HAP/VAP. The data we generate will be useful clinically in identifying
those patients who require aggressive management and scientifically in providing a deeper understanding of the
pathogenesis of HAP/VAP.

## Key facts

- **NIH application ID:** 10757344
- **Project number:** 5U19AI135964-07
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ALAN R HAUSER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,789
- **Award type:** 5
- **Project period:** 2018-01-17 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757344

## Citation

> US National Institutes of Health, RePORTER application 10757344, Systems Biology Modeling of Severe Hospital-Acquired Pneumonia (5U19AI135964-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10757344. Licensed CC0.

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