R01ES036966

RESIDENTIAL GREENNESS, AIRWAY MICROBIOME,AND INCIDENT CHILDHOOD ASTHMA - THE MAJOR CHALLENGES FOR DEVELOPING PRIMARY PREVENTION STRATEGIES FOR CHILDHOOD ASTHMA ARE THE EARLY IDENTIFICATION OF MODIFIABLE RISK FACTORS (E.G., ENVIRONMENTAL FACTORS, MICROBIOME) AND THE HETEROGENEITY OF ASTHMA. OUR GROUP HAS APPLIED INTEGRATED OMICS APPROACHES TO INFANCY DATA, AND IDENTIFIED ENDOTYPES AT HIGH RISK FOR ASTHMA. NO STUDY HAS EXAMINED THE INTEGRATED ROLE OF RESIDENTIAL GREENNESS, AIRWAY MICROBIOME (BOTH COMPOSITION AND FUNCTIONAL CAPACITY), AND HOST RESPONSE DURING INFANCY IN THE DEVELOPMENT OF CHILDHOOD ASTHMA AND ITS PHENOTYPES. OUR CENTRAL HYPOTHESIS IS THAT AN INTERRELATION BETWEEN THE RESIDENTIAL, AIRWAY MICROBIOME, AND THE HOST WILL SHAPE EARLYLIFE IMMUNITY AND CONTRIBUTE TO THE DEVELOPMENT OF ASTHMA AND ITS PHENOTYPES. WE WILL LEVERAGE AIRWAY SAMPLES AND COMPREHENSIVE ENVIRONMENTAL, CLINICAL, AND OMICS DATA FROM THREE MULTICENTER PROSPECTIVE COHORTS. THE 30TH MULTICENTER AIRWAY RESEARCH COLLABORATION FINLAND (MARC-30 FINLAND) IS AN ONGOING MULTICENTER COHORT STUDY OF 408 INFANTS WITH SEVERE BRONCHIOLITIS. THE MARC-35 (U01 AI087881) IS AN ONGOING MULTICENTER COHORT STUDY OF 919 INFANTS WITH SEVERE BRONCHIOLITIS. THE MARC-43 (UG3/UH3 OD023253) IS AN ONGOING MULTICENTER COHORT STUDY OF 599 HEALTHY INFANTS. THE PRESENT R01 PROJECT WOULD EXTEND THESE WELL-PHENOTYPED COHORTS BY GENERATING THE RESIDENTIAL GREENNESS INDICES (NORMALIZED DIFFERENCE VEGETATION INDEX AND GREEN CHLOROPHYLL INDEX), SEQUENCING AIRWAY METAGENOME AND THEN EXAMINING THEIR RELATIONS TO THE DEVELOPMENT OF ASTHMA AND ITS PHENOTYPES BY AGE 6-7 YEARS. IN AIM 1, WE WILL IDENTIFY THE INTEGRATED ROLE OF RESIDENTIAL GREENNESS AND AIRWAY METAGENOME ON DEVELOPING ASTHMA (AND ITS PHENOTYPES) IN SEVERE BRONCHIOLITIS INFANTS (MARC-30 FINLAND AND MARC-35). IN AIM 2, WE WILL IDENTIFY THE INTEGRATED ROLE OF RESIDENTIAL GREENNESS, AIRWAY METAGENOME, AND HOST GENOME, ON DEVELOPING ASTHMA (AND ITS PHENOTYPES) IN SEVERE BRONCHIOLITIS INFANTS (MARC-35 ONLY). IN AIM 3, TO EXAMINE THE REPRODUCIBILITY AND GENERALIZABILITY OF FINDINGS FROM AIMS 1-2, WE WILL IDENTIFY THE INTEGRATED ROLE OF RESIDENTIAL GREENNESS, AIRWAY METAGENOME, AND HOST GENOME, ON DEVELOPING ASTHMA (AND ITS PHENOTYPES) IN HEALTHY INFANTS (MARC-43 ONLY). THE ENVIRONMENTAL (I.E., RESIDENTIAL GREENNESS AND AIR POLLUTION) AND METAGENOME DATA GENERATED BY THIS R01 PROJECT—ALONG WITH PARALLEL MULTI-OMICS (E.G., GENOME, DNA METHYLOME, TRANSCRIPTOME, METABOLOME) AND IMMUNOLOGICAL DATA AVAILABLE—OFFER AN UNPRECEDENTED OPPORTUNITY TO DEVELOP DATA-DRIVEN MECHANISTIC MODELS FOR CHILDHOOD ASTHMA AND HIGHLIGHT PREVENTIVE STRATEGIES BASED ON THE MODIFIABLE RISK FACTORS.

The General Hospital Corporation

TO FOSTER UNDERSTANDING OF HUMAN HEALTH EFFECTS OF EXPOSURE TO ENVIRONMENTAL AGENTS IN THE HOPE THAT THESE STUDIES WILL LEAD TO: THE IDENTIFICATION OF AGENTS THAT POSE A HAZARD AND THREAT OF DISEASE, DISORDERS AND DEFECTS IN HUMANS, THE DEVELOPMENT OF EFFECTIVE PUBLIC HEALTH OR DISEASE PREVENTION STRATEGIES, THE OVERALL IMPROVEMENT OF HUMAN HEALTH EFFECTS DUE TO ENVIRONMENTAL AGENTS, THE DEVELOPMENT OF PRODUCTS AND TECHNOLOGIES DESIGNED TO BETTER STUDY OR AMELIORATE THE EFFECTS OF ENVIRONMENTAL AGENTS, AND THE SUCCESSFUL TRAINING OF RESEARCH SCIENTISTS IN ALL AREAS OF ENVIRONMENTAL HEALTH RESEARCH. SUPPORTED GRANT PROGRAMS FOCUS ON THE FOLLOWING AREAS: (1) UNDERSTANDING BIOLOGICAL RESPONSES TO ENVIRONMENTAL AGENTS BY DETERMINING HOW CHEMICAL AND PHYSICAL AGENTS CAUSE PATHOLOGICAL CHANGES IN MOLECULES, CELLS, TISSUES, AND ORGANS, AND BECOME MANIFESTED AS RESPIRATORY DISEASE, NEUROLOGICAL, BEHAVIORAL AND DEVELOPMENTAL ABNORMALITIES, CANCER, AND OTHER DISORDERS, (2) DETERMINING THE MECHANISMS OF TOXICITY OF UBIQUITOUS AGENTS LIKE METALS, NATURAL AND SYNTHETIC CHEMICALS, PESTICIDES, AND MATERIALS SUCH AS NANOPARTICLES, AND NATURAL TOXIC SUBSTANCES, AND THEIR EFFECTS OF ON VARIOUS HUMAN ORGAN SYSTEMS, ON METABOLISM, ON THE ENDOCRINE AND IMMUNE SYSTEMS, AND ON OTHER BIOLOGICAL FUNCTIONS, (3) DEVELOPING AND INTEGRATING SCIENTIFIC KNOWLEDGE ABOUT POTENTIALLY TOXIC AND HAZARDOUS CHEMICALS BY CONCENTRATING ON TOXICOLOGICAL RESEARCH, TESTING, TEST DEVELOPMENT, VALIDATION AND RISK ESTIMATION, (4) IDENTIFYING INTERACTIONS BETWEEN ENVIRONMENTAL STRESSORS AND GENETIC SUSCEPTIBILITY AND UNDERSTANDING BIOLOGIC MECHANISMS UNDERLYING THESE INTERACTIONS, INCLUDING THE STUDY OF ENVIRONMENTAL INFLUENCES ON EPIGENOMICS AND TRANSCRIPTIONAL REGULATION, (5) CONDUCTING ENVIRONMENTAL PUBLIC HEALTH RESEARCH, INCLUDING IN AREAS OF ENVIRONMENTAL JUSTICE AND HEALTH DISPARITIES, THAT REQUIRES COMMUNITIES AS ACTIVE PARTICIPANTS IN ALL STAGES OF RESEARCH, DISSEMINATION, AND EVALUATION TO ADVANCE BOTH THE SCIENCE AND THE DEVELOPMENT OF PRACTICAL MATERIALS FOR USE IN COMMUNITIES, WITH A FOCUS ON TRANSLATING RESEARCH FINDINGS INTO TOOLS, MATERIALS, AND RESOURCES THAT CAN BE USED TO PREVENT, REDUCE, OR ELIMINATE ADVERSE HEALTH OUTCOMES CAUSED BY ENVIRONMENTAL EXPOSURES, (6) EXPANDING AND IMPROVING THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) EXPANDING AND IMPROVING THE STTR PROGRAM TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (8) PROVIDING SUPPORT FOR BROADLY BASED MULTI-DISCIPLINARY RESEARCH AND TRAINING PROGRAMS IN ENVIRONMENTAL HEALTH .THESE PROGRAMS INCLUDE THE ENVIRONMENTAL HEALTH SCIENCES CORE CENTERS , WHICH SERVE AS NATIONAL FOCAL POINTS AND RESOURCES FOR RESEARCH AND MANPOWER DEVELOPMENT. THROUGH THESE PROGRAMS, NIEHS EXPECTS TO ACHIEVE THE LONG-RANGE GOAL OF DEVELOPING NEW CLINICAL AND PUBLIC HEALTH APPLICATIONS TO IMPROVE DISEASE PREVENTION, DIAGNOSIS, AND THERAPY. ADDITIONAL CENTERS PROGRAMS DEVELOPED IN RECENT YEARS, INCLUDE THE CENTERS FOR OCEANS AND HUMAN HEALTH (CO-FUNDED WITH NSF), CHILDREN'S ENVIRONMENTAL HEALTH CENTERS (CO-FUNDED WITH US EPA) AND THE AUTISM CENTERS OF EXCELLENCE (CO-FUNDED WITH OTHER NIH INSTITUTES), AND THE HUMAN HEALTH EXPOSURE ANALYSIS RESOURCE (HHEAR) PROGRAM, (9) SUPPORTING RESEARCH TRAINING PROGRAMS WHICH SERVE TO INCREASE THE POOL OF TRAINED RESEARCH MANPOWER WITH NEEDED EXPERTISE IN THE ENVIRONMENTAL HEALTH SCIENCES THROUGH SUPPORT OF INDIVIDUAL AND INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS), (10) THE OUTSTANDING NEW ENVIRONMENTAL SCIENTIST PROGRAM WHICH PROVIDES FIRST TIME RESEARCH GRANT FUNDING TO OUTSTANDING JUNIOR SCIENTISTS IN THE FORMATIVE STAGES OF THEIR CAREER WHO ARE PROPOSING TO MAKE A LONG TERM COMMITMENT TO ENVIRONMENTAL HEALTH SCIENCES RESEARCH AND TO ADDRESS THE ADVERSE EFFECTS ON ENVIRONMENTAL EXPOSURES ON HUMAN BIOLOGY, HUMAN PATHOPHYSIOLOGY AND HUMAN DISEASE.

93.113 - Environmental Health

National Institute of Environmental Health Sciences (NIEHS) [HHS - NIH]

Massachusetts United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)