R01HL152475

Nasal Epithelial Epigenomics and Transcriptomics and Asthma in Hispanic Adults - Abstract

Genes associated with asthma are often expressed in airway epithelium, and such epithelium regulates immune responses to environmental challenges and airway inflammation. Thus, epigenetic regulation and gene expression in airway epithelium could be key to asthma pathogenesis.

Indeed, we recently identified biologically plausible DNA methylation and transcriptomic markers of atopic asthma in airway (nasal) epithelium of children and adolescents of Puerto Rican, African American, and European descent. Such markers are located in or near genes related to immune regulation and airway epithelial integrity and function, yet most were not identified by GWAS.

Moreover, we developed nasal methylation and transcriptomic profiles that accurately classified subjects by atopic asthma in a cross-sectional study. In contrast to these findings in children, little is known about the underlying mechanisms or predictors of asthma in Hispanic adults, including Puerto Rican and Dominican adults.

Lack of such knowledge is an important problem because, without it, gaining the ability to prevent or treat asthma morbidity in this underserved group is highly unlikely. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) provides a unique opportunity to examine DNA methylation and gene expression in airway epithelium and asthma, lung function, and asthma outcomes in Puerto Rican and Dominican adults.

On the basis of our novel preliminary results, we hypothesize that altered expression of genes that regulate airway epithelial function and immune responses are associated with asthma, lung function, and asthma severity or control in Puerto Rican and Dominican adults.

To test this hypothesis, we will first conduct a genome-wide (GW) study of association between DNA methylation in nasal (airway) epithelium from 900 Puerto Rican and Dominican adults in HCHS/SOL and asthma, lung function and lung function decline, and asthma control or severity, and develop predictive or classification models of asthma outcomes.

We will then perform a GW study of association between gene expression in nasal epithelium in the same subjects as in SP. Aim 1 and asthma, lung function and lung function decline, and asthma control or severity, and develop predictive or classification models of asthma outcomes.

Next, we will conduct expression quantitative trait locus (eQTL) analysis and expression quantitative trait methylation (eQTM) analyses to integrate the results from available GW genotypic data with those from the analyses of methylation and expression (conducted in SP. Aims 1 and 2), and perform a pathway analysis and functional validation studies for the top genes.

This proposal will address an important, yet unstudied, aspect of asthma "omics": the identification of epigenomic and transcriptomic markers and/or determinants of asthma outcomes among adults in two Hispanic subgroups at intermediate to high risk of asthma (Dominicans and Puerto Ricans).

To achieve this goal, we have assembled an outstanding multidisciplinary research team.

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Pittsburgh, Pennsylvania 152133203 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 384% from $699,612 to $3,386,733.