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Record Count: 3
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header (Title, Principal Investigator, Institution, City, ST, Award Code, or
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DESCRIPTION (provided by applicant)
This proposal is submitted in response to the RFA-ES-06-001 DISCOVER initiative. The fetus and young child have physiologic, developmental, metabolic, and behavioral patterns that make them uniquely vulnerable to hazards in their environments. Ambient air pollution has been implicated as a major risk factor for asthma and asthma exacerbation, however epidemiological studies have been hampered by uncertainties in exposures and the nature of airway responses. The Columbia Center for Children's Environmental Health (CCCEH) Disease Investigation through Specialized Clinically-Oriented Ventures in Environmental Research (DISCOVER) seeks to understand when and how airborne polycyclic aromatic hydrocarbons (PAHs) and diesel exhaust particles (DEP) increase the risk for childhood asthma and airway inflammation, develop new biomarkers to identify children at risk and improve clinical treatment, evaluate the success of a public policy intervention, and implement physician education initiatives as a mode of intervention. This proposal includes four closely linked projects and Administrative and Data Management and Biostatistics Cores each ensuring the seamless coordination of the multiple research activities involved in this proposal. The cores play vital roles in the quality of research information and statistical analyses and the administrative/financial oversight and translational components of the four main DISCOVER research project initiatives. The four project aims are: 1) Take advantage of repeat PAH measurements pre- and post-natally to distinguish between the biological effects of prenatal PAH exposure versus postnatal exposure during early childhood and pre-adolescence; 2) To advance the understanding of the influence of diesel exhaust exposures, which include PAHs, in acute asthma exacerbations by linking innovative exposure and outcome measures; 3) To determine whether epigenetic changes related to PAH exposure are involved in the pathogenesis of childhood asthma; 4) To ascertain if traffic related PAHs affect ?2AR function in airway smooth muscle cells in vitro, alter (?2AR function following in utero and early life exposures, affect (?2AR expression and function in airway epithelial cells in vitro. The research is translational to asthma prevention, clinical treatment, physician education, and policy.
INTEGRATED (clinical and basic) and INTERDISCIPLINARY NATURE OF PROGRAM
Description: The goal of the DISCOVER Center submitted by Dr. Perera, Columbia University, is to expand the work of the existing Columbia Center for Children's Environmental Health (CCCEH) to understand how and when airborne polycyclic aromatic hydrocarbons (PAHs) and diesel exhaust particles (DEP) increase the risk for childhood inflammation and asthma. The Center will also develop new biomarkers to identify children at risk and improve clinical treatment, evaluate the success of a public policy intervention and implement physician education initiative as a mode of intervention.
DESCRIPTION (provided by applicant)
The overall objective of this DISCOVER Center is to investigate the mechanisms by which traffic-related air pollution causes myocardial infarction and other cardiovascular diseases, by integrating a diverse set of research approaches. Air pollution exposures have been consistently associated with cardiovascular disease. A growing literature indicates that the major source of variation in air pollution's cardiovascular health effects is from exposure to traffic. Diesel exhaust is an excellent model exposure. The closely linked suite of activities in this DISCOVER Center will attempt to understand the mechanisms (molecular mechanisms that cause vasoconstriction and acceleration of atherosclerosis) underlying exposure-related effects, and use environmental exposures to understand basic mechanisms regarding vascular biology. The studies will exploit exposure contrasts in experimental and epidemiological studies through advanced exposure assessment methods, and genetic diversity in both human and animal studies, to advance our aims. The application brings together a cohesive group of five projects (two patient-oriented and three basic mechanistic studies) and three cores, Administrative, Exposure Science, and Biostatistics and Bioinformatics. Project 1 investigates the mechanism underlying vascular response in humans following controlled exposure to diesel exhaust; Project 2 studies genetic modifiers on the effect of traffic-related air pollution on vascular response and atherosclerosis in a population-based human observational study. Project 3 investigates the role of systemic inflammation in the vascular response to diesel exhaust. Project 4 investigates the impact of diesel exhaust exposure on myocardial injury and apoptosis. Project 5 investigates reactive oxygen species and oxidative stress in the vascular response to diesel exhaust. Through this research, the investigators will develop knowledge that can be used to develop preventive and therapeutic strategies.
INTEGRATED (clinical and basic) and INTERDISCIPLINARY NATURE OF PROGRAM
DESCRIPTION (provided by applicant)
The long-term goal of the Center for Childhood Asthma in the Urban Environment (CCAUE) is to understand how exposures to indoor and outdoor airborne particulate matter and allergens may result in airway inflammation and respiratory morbidity in children with asthma living in the inner city of Baltimore and to identify novel opportunities and strategies to reduce morbidity associated with these exposures. The overarching hypothesis guiding the Center's proposed research is that indoor air pollution (particulate matter and allergens) produces increased oxidative stress which leads to increased airway inflammation and asthma morbidity in children. The investigators have assembled a multidisciplinary and integrated team of researchers to investigate the role oxidative stress, and airway inflammation in asthma morbidity in order to develop new biomarkers of effect, provide insight into susceptible genotypes, offer better clinical management, and to identify opportunities for intervention (environmental and pharmacologic).
This program outlines a multidisciplinary program directed to address this hypothesis and long-term goal. This Center application includes the following two clinically-oriented and mechanistically-oriented research projects: Clinically-Oriented Research Projects: Project 1 - Domestic Indoor PM and Childhood Asthma Morbidity; Project 2 - Oxidative Stress/Inflammation during PM Nasal Challenge and Mechanistically-Oriented Research Projects: Project 3 - Nrf2 Dependent Regulation of Oxidative Stress in Asthma; Project 4 - Mechanisms of PM-Induced Dendritic Cell Activation.
INTEGRATED (clinical and basic) and INTERDISCIPLINARY NATURE OF PROGRAM
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