# Bioengineered Multi-Cell Type Organoids For Airways Disease Modeling

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $436,447

## Abstract

PROJECT SUMMARY
Respiratory diseases are among the leading causes of death worldwide. Respiratory disease caused by
smoking, infections, and genetic factors together account for approximately 9.5 million deaths per year.
Respiratory infection is the 3rd most common cause of death worldwide, and the leading cause of death in
developing countries. Genetic risk factors are significant contributors to lung disease prevalence. For example,
cystic fibrosis (CF) is ranked as one of the most widespread life-shortening genetic diseases2-4 with more than
70,000 people currently living with CF. Due to the high incidence; respiratory diseases are also among the
most studied medical conditions. The study of respiratory diseases is significantly limited by a lack of suitable
in vivo and in vitro models to investigate interactions between the respiratory epithelium, infection, and
disease. Unfortunately animal models of lung disease differ significantly from humans in airway development
and disease pathology, so often result in inaccurate and significantly flawed models, While some progress has
been made in using human cell culture systems for disease modeling and drug discovery, current in vitro
models are unable to reproduce the complex spatial morphology and allow biologically relevant cell-cell and
cell-matrix interactions. The overall premise for the proposed work is that (a) in vivo animal models often differ
significantly from humans in disease pathology and have significant cost limitations; and (b) current in vitro
models of respiratory disease and bacterial pathogenesis do not recapitulate the complex tissue components
and 3D architecture of the human airway epithelium. This collaborative R01 proposal is motivated by the
critical need to address the current gaps and knowledge and overcome the limitations of current in vitro 2D cell
culture models for airway disease modeling, therapy development, and pre-clinical testing. Our overall
hypothesis is that recapitulation of the in vivo airway microenvironment will provide a more effective in vitro
surrogate for airway disease modeling and therapy evaluation. To test this hypothesis, we will first generate
bioengineered multicellular 3D airway organoids, supported by a lung extracellular matrix (ECM)-derived biogel
with tunable biomechanical properties, to promote multicellular organization and function of healthy airway
epithelium (Aim 1). Next we will evaluate whether 3D airway organoids containing CF airway epithelium can
model disease pathology (Aim 2). Finally we will use this novel airway disease model to study the
pathogenesis of P. aeruginosa (Aim 3). If awarded, this collaborative R01 will allow our multi-disciplinary and
multi-institutional team to develop and evaluate 3D airway organoids as a more effective in vitro surrogate for
airway disease modeling and therapy evaluation. Likely developments building on this work could include use
of patient-specific airway organoid models for testing of per...

## Key facts

- **NIH application ID:** 10201733
- **Project number:** 5R01HL143076-03
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sean Vincent Murphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $436,447
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201733

## Citation

> US National Institutes of Health, RePORTER application 10201733, Bioengineered Multi-Cell Type Organoids For Airways Disease Modeling (5R01HL143076-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10201733. Licensed CC0.

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