# Quantitative analysis of mucociliary clearance in airway ciliopathies

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $624,431

## Abstract

PROJECT SUMMARY
Mucociliary clearance (MCC) is a critical mechanical defense mechanism of the human respiratory system.
Poor MCC is a fundamental feature of many inherited and acquired respiratory diseases including primary
ciliary dyskinesia (PCD), asthma, chronic bronchitis, and cystic fibrosis (CF). Due to the complex organization
of the lung, it is largely unknown how defects of the ciliary machinery change functional MCC and how regional
variability of airway epithelial structure, including cell type proportions and ciliary beat parameters, affect local
MCC pathophysiology. These knowledge gaps dramatically impair our ability to predict the degree of pulmonary
dysfunction imparted by specific ciliary defects, and to understand the airway region-specific onset observed in
many lung diseases. While impaired MCC is a pre-determined functional consequence of PCD and other
chronic lung diseases, to date, there is no established in vitro model that is able to accurately predict the
relationship between genotype, cilia motility, MCC, and respiratory phenotype and, therefore, many
genotype-phenotype relationships remain unexplained. Our transdisciplinary research program is designed
to address an unmet need to understand how a) region-specific airway organization and b) ciliopathy-
causing genotypes, impact MCC. To achieve this we will complete specific aims designed to: 1) use ex vivo
lung tissues, that retain their in vivo epithelial organization, as models of ciliated airway epithelia to
comprehensively evaluate biomechanical structure-function relationships in large and small airways (Aim 1); 2)
use established in vitro models of the human tracheo-bronchial (large) airways to determine a minimal set of
structural and functional parameters that are conserved between in vitro and ex vivo ciliated tissues (Aim 2); 3)
apply state-of-the-art physics-based computational approaches to develop an in silico model that will be able
to predict structure-function relationships of ciliated tissues (Aim 3) and 4) use the minimal set of parameters
that define functional MCC in both in vitro and ex vivo models as input into the in silico model to predict regional-
specific changes in MCC due to ciliary defects in both large and small airways (All Aims). Our specific objectives
build to our long-term goal of combining in vitro and in silico models as a preclinical, precision medicine
tool for evaluating small molecule or gene-editing therapeutics toward more targeted and efficient
treatment regimens of pulmonary diseases characterized by poor mucociliary clearance.

## Key facts

- **NIH application ID:** 10212158
- **Project number:** 1R01HL153622-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Eva Kanso
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $624,431
- **Award type:** 1
- **Project period:** 2021-04-23 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212158

## Citation

> US National Institutes of Health, RePORTER application 10212158, Quantitative analysis of mucociliary clearance in airway ciliopathies (1R01HL153622-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10212158. Licensed CC0.

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