# Lung-on-a-Chip Disease Models for Efficacy Testing

> **NIH NIH UH3** · HARVARD UNIVERSITY · 2020 · $1,413,750

## Abstract

SUMMARY
 The goal of this proposal is to use Organs-on-Chips (Organ Chips) to develop clinically relevant in vitro
models of influenza infection in humans that can be used to test efficacy of candidate therapeutics, explore
variation in responses in different patient populations, and potentially develop anti-influenza drugs that target
the host response to infection, rather than the virus itself. Our Organ Chips are 2-channel microfluidic culture
devices that are lined by human organ-specific tissue cells and vascular endothelium grown in parallel
microchannels separated by a porous extracellular matrix-coated membrane. We have previously created
Lung Alveolus Chips as well as Small Airway Chips lined by bronchiolar epithelial cells from either normal
donors or diseased patients, such as individuals with chronic obstructive pulmonary disease (COPD), and we
showed that they faithfully recapitulate human pathophysiology observed in vivo, including lung inflammation
and pulmonary edema In addition, we have created human Liver Chips that metabolize drugs in vitro, and
engineered an instrument for automated culture and fluidic coupling of up to 10 human organ chips for up to 4
weeks, which can be used to link different Organ Chips in a physiological way. Importantly, in preliminary
studies, we successfully infected these bronchiolar epithelium with H1N1 influenza A virus (IAV), identified
molecular mediators of the host response to infection, and discovered a potential new antiviral therapeutic that
targets these mediators. In the UG3 phase of this project, we will demonstrate that Lung Airway and Alveolus
Chips lined by primary cells isolated from human healthy donors or COPD patients can be used to model
clinical features of IAV infection and related lung disorders previously observed in human patients, including
viral replication and shedding, release of characteristic inflammatory cytokines, recruitment of circulating
immune cells, and pulmonary edema, all of which we will measured non-invasively. During the UH3 phase, we
will conduct preclinical efficacy testing of existing antiviral drugs and use multi-omics analysis and
bioinformatics approaches to define translatable biomarkers and identify new potential molecular targets. We
also will leverage these insights to discover new potential therapeutics that target the host response to
infection, rather than the virus itself. Our UG3 Specific Aims are 1) to develop models of influenza infection in
human Lung Airway and Alveolus Chips lined by cells from healthy donors and COPD patients that recapitulate
in vivo disease responses, and 2) to develop an integrated model for influenza drug testing by fluidically linking
Lung Airway, Lung Alveolus Chips, and Liver Chips via their vascular channels. Our UH3 Aims include: 1) to
use the integrated Organ Chip influenza model to measure efficacy and safety of known antiviral therapeutics,
2) to validate translatable biomarkers for influenza infection and ther...

## Key facts

- **NIH application ID:** 9995558
- **Project number:** 5UH3HL141797-04
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** DONALD E INGBER
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,413,750
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995558

## Citation

> US National Institutes of Health, RePORTER application 9995558, Lung-on-a-Chip Disease Models for Efficacy Testing (5UH3HL141797-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9995558. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*