Effects of Bisphenol A (BPA) on Asthma Pathogenesis
PI: Terumi Midoro-Horuiti, MD and Ph.D.; Co-I: Shuk-mei Ho, Ph.D.
The proposed project will focus on one of the existing NIEHS Center's theme "asthma pathogenesis." The long-term goal of our research is to elucidate the role of environmental estrogens, such as bisphenol A (BPA), in the development of asthma and other allergic diseases. The prevalence of asthma, particularly in children in industrialized countries has increased dramatically over the last 2-3 decades and is now the most common chronic disease of children in the U.S. Given the magnitude of the problem of childhood asthma and the evidence that asthma at any age usually has its genesis in childhood, the impact of the proposed studies on public health and the health care delivery system is likely to be very large.
We have recently shown in an animal model that perinatal exposure of BPA enhanced development of asthma. This project will rapidly expand ongoing efforts on two campuses, to define the role for BPA in early immunologic development that underlies asthma and other common allergic diseases. The magnitude and complexity of this important new endeavor has required the assembly of a multidisciplinary research team and may subsequently require an expansion of the relevant scientific enterprise to complete this critical task. The general approach will be to identify the epigenetic, cellular and functional biomarkers of BPA exposure and asthma in the groups of high and low cord blood serum BPA. An animal model of the effect of BPA on a developmental model of allergic asthma, currently functioning in Galveston and an evolving gene discovery platform in Cincinnati, will allow our team to ask a number of important questions about the effects of maternally-derived BPA on the development of asthma in their infants. This translational project will allow our team to move smoothly between our animal model of asthma and a new human cohort study to examine the relationship between early life BPA exposure and the development of asthma.
The specific question we plan to answer in this project is: Does exposure of the human fetus to ambient levels of BPA induce biomarkers of exposure that are similar to those seen in the infant mouse model and are functionally related to the development of asthma? Our answers to this question should inform public health policies for preventing future toxic exposures and promote the development of approaches to interrupting the long-term toxicity of BPA. If the integrated, scientific approach we will use in this project works smoothly, it will be strong basis for extramural funding. This system will also lay the foundation for other environmental studies that strive to establish causal or facilitative relationships between specific toxicants and human diseases.
