Administrative Core Search Clinical Trials Find a Researcher Order a Test The Administrative Core coordinates the scientific activities of the program, organizes regular meetings of the internal and external advisory committees, responds to requests from NIEHS/EPA, allocates budgets in accordance with NIH policies, and centralizes certain budgetary items for the program investigators. In addition, the Administrative Core assumes responsibility to coordinate the recruitment, support, and evaluation of new junior-faculty level investigators in the Center. Core Leaders: David A. Schwartz, MD and Stanley J. Szefler, MD Faculty Development Investigator Award Purpose: To foster the next generation of creative new scientists in children’s environmental health, the Denver CEHC plans to support the research career development of new, junior faculty-level investigators in basic, clinical, translational or population based research. The Awardee will receive $50,000 per year for up to 2 years of non-salary support. Year 2 funding will depend on academic development in the 1st year of funding and the availability of funding from the CEHC. Requirements: The Faculty Development Investigator (FDI) may hold either a health professional doctorate (M.D., D.O, Pharm. D., doctoral degree in nursing, or other equivalent degree) or a research doctoral degree (Ph.D., or equivalent), should have fewer than eight years of postdoctoral experience (excluding clinical training years) at the time the application is submitted, and should have demonstrated outstanding abilities in basic, clinical or population based research. The applicant must meet the NIH definition of New Investigator. The applicant’s research proposal should be related to children’s environmental health, including but not limited to airway disease. In addition, the applicant must have a long-term commitment to research in the environmental health sciences. Expectations of Awardee: The Awardee is expected to devote a minimum of 30% time and effort to the project, provide two presentations to the CEHC group each year, and to submit a brief annual report. Deadline and Application: Eva Laemmerhirt Academic Administrative Assistant Department of Medicine University of Colorado Denver 12631 East 17th Avenue, B178 Aurora, CO 80045 303.724.5855 Eva.Laemmerhirt@ucdenver.edu Current Awardees Beata Kosmider, PhD Project Title: Lung injury in children induced by ozone and influenza A virus. Abstract: Ozone and influenza A virus (IAV) are well known environmental factors that cause lung injury and worsen lung inflammation, especially in susceptible populations such as children. To define the mechanism of this tissue injury, it is important to study the cells that actually get exposed to these factors and contribute to severe morbidity and mortality. Therefore, we are focusing on the cells in the gas exchange portion of the pediatric lung. We expect that exposure to ozone will increase susceptibility to IAV. Our hypothesis is that the nuclear factor erythroid 2-related factor 2 (Nrf2) will protect against injury produced by both ozone and IAV and the interaction between these two pro-oxidant environmental factors. Nrf2 is the principle transcription factor that regulates expression of phase II detoxifying antioxidant enzymes. We plan to study the mechanisms of protective effect of Nrf2 using its overexpression or knockdown. Our studies will be extended to include a translational approach by determining the role of resveratrol or sulforaphane, which are Nrf2 activators, as potential preventive strategies. Our approach is unique in that we will study the effect of ozone and IAV on alveolar type II (ATII) cells and alveolar macrophages (AM) isolated from the same lung donors so that the response of these important cell types can be compared in the same genetic background. Results of the responsiveness of the Nrf2 pathway in pediatric lung cells will improve our understanding of the etiology and pathogenesis of lung disease in children and potentially lead to therapeutic targets. Hypothesis: Chlorine inhalation in the juvenile rat lung will result in dose-dependent changes in lung injury-specific and chlorine-specific biomarkers in serum and BALF. Specific Aims: To determine cell injury in ATII cells and AM from children after exposure to ozone and IAV in vitro and protective effects of resveratrol or sulforaphane. To determine ATII cell and AM injury after exposure to ozone, A/PR/8/34 and A/Cal/2009 (H1N1 2009 pdm) viruses. To determine the protective effect of resveratrol or sulforaphane against ATII cell and AM injury induced by ozone and IAV. To determine the importance of Nrf2 in the cell injury induced by ozone and IAV in ATII cells and AM from children in vitro. To determine if reduction of Nrf2 in ATII cells and AM will sensitize these cells to exposure to ozone and IAV. To determine whether Nrf2 overexpression in ATII cells will protect these cells against injury induced by exposure to ozone and IAV. Livia Veress, MD Project Title: Sensitive biomarkers detecting chlorine effects in the juvenile lung Abstract: Chlorine is a highly utilized compound in industry and society, with massive exposure potential due to transportation accidents, industry exposures, or chemical terrorism. Recurrent chlorine exposure can occur during routine attendance at swimming pools, as in competitive swimmers or lifeguards, or from frequent recreational swimming, including swimming by infants and toddlers. Recent studies report an increased prevalence of asthma in all recreational swimmers, most notably in lifeguards and competitive swimmers who spend long hours in a high chlorine environment. At present, it is unclear why chlorine exposure increases development of an asthma-like phenotype, Based on existing literature, Dr. Veress hypothesizes that chlorine inhalation in juvenile rats will result in dose-dependent airway injury that will cause corresponding changes in several biomarkers, both in serum and bronchoalveolar lavage fluid (BALF). Lung injury and potential biomarkers will be measured in lung, BALF and serum. These include surfactant proteins A and D, Clara cell specific protein (CCSP), 3-chlorotyrosine and the 75kDa inactivated product of sarcoendoplasmic reticulum calcium ATPase (SERCA). These will be correlated with extent of injury observed per airway generation, visualized by microdissection, using a live/dead assay by confocal microsocopy. Her objective is to develop biomarkers of chlorine injury that ultimately can be used to detect children at risk for developing asthma after chlorine exposure. Emphasis is placed on determining the most sensitive and stable biomarkers, and those having greatest correlation with degree of lung injury. Hypothesis: Chlorine inhalation in the juvenile rat lung will result in dose-dependent changes in lung injury-specific and chlorine-specific biomarkers in serum and BALF. Specific Aims: Delineate temporal, spatial and dosimetric relationships of the lung injury-specific biomarkers SPA, SP-D and CCSP in serum, lung, and BALF after chlorine exposure, and subsequently correlate these biomarker levels with the changes observed within lung tissue. Determine temporal, spatial and dosimetric relationships of the chlorine-specific biomarker chlorotyrosine, in serum, lung, and BALF after chlorine exposure, and subsequently correlate these biomarker levels with the changes observed within lung tissue. Assess involvement of SERCA inactivation or fragmentation, both as biomarker and potential mechanism for development of asthma after chlorine inhalation injury.