Integrative-omics of the Disordered COPD Small Airway Epithelium

Completed

• Conditions: COPD; Smoking

• Registration Number: NCT02183818
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

We aim to use an integrated network systems approach to analyze certain existing small airway epithelium (SAE) omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomic levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.

Detailed Description

Hypothesis: We hypothesize that the disordered differentiation of the SAE that characterizes COPD results from the complex interaction of cigarette smoke components with a hierarchy of genetic, epigenetic, gene expression and metabolomics network interactions as the BC differentiate into a mucociliary epithelium.

Specific aim 1. Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.

Specific aim 2. To refine the model, a comprehensive omics data set will be collected at multiple time points as SAE BC of nonsmokers and COPD smokers differentiate to normal and disordered mucociliary epithelium (respectively) on air-liquid interface (ALI) culture, an in vitro model of SAE differentiation. The computational strategies from aim 1 will be used to improve the model with these data.

Specific aim 3. To test and finalize the integrated network model, a parallel omics data set will be generated from BC from nonsmokers, and COPD smokers as they differentiate on ALI under conditions where key hubs will be up- or down-regulated and the differentiation process stressed under conditions mimicking the in vivo SAE environment. The end result will be an integrated systems model of SAE biology and how this is disordered in COPD.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-06-17
• Study First Submitted QC: 2014-07-02
• Study First Posted: 2014-07-08
• Study Start: 2015-04-06
• Primary Completion: 2016-11-17
• Study Completion: 2020-10-15
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-26
• Last Update Posted: 2021-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets.	One Year	Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States