Dr. Schelegle directs a translational program that examines how environmental factors affect human lung health. This translational program includes both animal and human studies. Dr. Schelegle's primary research interest is pulmonary neurophysiology with a focus on the role that lung vagal afferents play in the control of breathing, epithelial injury, inflammation and repair in models of acute and chronic lung injury and/or disease. Publications in this area examine the contribution of pulmonary afferents to the altered breathing pattern, epithelial injury, inflammation and repair in animal models of acute airway injury. Specifically these studies address how the release of the neuropeptides, substance P and calcitonin gene related peptide (CGRP), from sensory lung afferents during and following acute lung injury orchestrate non-apoptotic programmed cell death in distal conducting airways and are required for the normal proliferation of epithelial cells in both proximal and distal airways. Human studies have focused on the mechanism of response to acute oxidant stress and markers of diseases involving the airway and pulmonary vasculature. As a Core Scientist Exposure Core at the California National Primate Research Center Dr. Schelegle has utilized primates to examine questions that are informed by observations made in rodent and human clinical studies.  As a result of this effort Dr. Schelegle has played a key role in developing models of adult and childhood asthma, and COPD in Rhesus macaques. The majority of  effort using nonhuman primates has been contributed to the design and execution of studies that examined the effect of early-life exposure to ozone on asthma severity.     Specific Areas of Investigation:    Pulmonary Neurophysiology - Since the work of Beuer in 1868 it has been known that the vagus nerves contain sensory nerves that send signals from the lungs to the brainstem. Since then four types of vagal sensory nerve types have been identified that innervate the lung, these include slowly adapting pulmonary stretch receptors (SARs), rapidly adapting pulmonary stretch receptors (RARs), and bronchial and pulmonary C-fibers. While most studies prior to 1990 examined the activation of these sensory nerves using mechanical and chemical stimuli and the reflexes evoked by each nerve type, while few had examined the role that these sensory nerves play in the models of lung diseases and acute injury. Beginning in 1993 Dr. Schelegle has multiple publications that characterize the pattern of activation of vagal sensory nerves in models of lung disease and acute lung injury and how this activation contributes to the control of breathing and symptoms. Publications in this area have contributed to a better understanding of the role that lungs sensory fibers play in pulmonary fibrosis, emphysema, asthma and ozone-induced airway injury.    Human Ozone Exposure-Response - With industrialization and the increased use of fossil fuels including coal and petroleum it has been recognized that the resulting air pollution can have adverse effects on human morbidity and mortality. The passage of the clean air act in 1963 and its' subsequent revision in 1970 greatly expanded the research of health effects of air pollution with a focus on identifying the exposure-response relationship for multiple "criteria air pollutants" that could then be used for establishing air quality standards for the purpose of regulating emissions. Beginning in 1984 Dr. Schelegle has multiple publications examining the factors that contribute to the exposure-response of ozone, a major constituent of photochemical air pollution, and the underlying events that contribute to ozone-induced adverse health effects in humans. Of these studies the data in my 2009 manuscript is one of two studies that are central to the US Environmental Protection Agency (EPA) proposal to lower the National Air Quality Standard for ozone from 75 ppb to 70 ppb. More recently Dr. Schelegle's work in this area has focused on improving risk assessment by developing a testable model of ozone exposure-response based on individual human subject response kinetics.    Neuropeptides in Lung Injury and Repair - The acute inhalation of the photochemical air pollutant, ozone, results in epithelial necrosis, inflammation and repair in animals and humans. With our observation that acute ozone inhalation in dogs activates bronchial C-fibers and the previous observation that C-fibers release neuropeptides in the tissue at the site of activation we began to investigate the role that lung C fiber afferents play in ozone-induced injury, inflammation and repair. Our findings to date demonstrate that the release of neuropeptides, substance P (SP) and calcitonin gene-relate peptide (CGRP) play a critical role in ozone-induced cell death and subsequent repair. Dr. Schelegle's observation that these mechanisms exist in rats and Rhesus macaques supports the notion that these mechanism play a role in ozone-induce injury response in humans and need to be considered when evaluating the adverse health effects of ozone in normal and susceptible human populations.