Faculty

Professor Aziz Ben-Jebria | Research

A) Inhalation Toxicology: Dr Ben-Jebria's main research interest is focused on the inhalation toxicology of air pollution. The effort is directed at understanding the mechanisms governing the transport dynamics of various pollutants into the respiratory system as well as their reaction kinetics with the substrates composing the fluid lining the airways of human lungs. Non-invasive clinical experimental methods are being developed to determine the longitudinal distribution of outdoor and indoor air pollutants absorption in human intact lungs under a variety of exposure situations (effects of: inhaled concentration, respiratory flow, exposure time) and physiological conditions (effects of breathing: at rest, during exercise, via oral versus nasal pathway). Because one of the hypotheses we want to test is whether the anatomical features of people respiratory tracts influence the dose distribution of the inhaled pollutants, we have designed non-invasive techniques to measure the volumes of three compartments of the respiratory tract (upper, central and distal airways) of each subject participating in the study; and because we want to test another hypothesis that the differences between subjects in their physiological responses to a pollutant exposure could be explained by the differences in their lung dosimetries, we are measuring the pulmonary function performance of each subject using spirometry tests. Concurrently with the experimental protocols, mathematical modeling and simulations are being developed to grasp the key fundamental transfer and reaction parameters that govern the uptake processes of those toxic chemicals in tissue lung airways. The objective is to formulate the relationships between tissue dose and the composition of the fluid lining the airways (antioxidants: uric acid, ascorbic acid, mucin, glutathione) as well as the physiological response.

B) Experimental Allergic Asthma:   Dr. Ben-Jebria's principal clinical research motivation is centered around the factors inducing airway hyper-reactivity that often occurs in people with asthma, the largest respiratory disease.  Asthma is indeed gaining prevalence in the U.S. with the greatest increase seen among inner city minority ethnics.  Among other factors, a complex interplay of genetic, socio-economic, behavioral, and environmental factors may play a role in this increase.  Patients with allergic asthma manifest airway inflammation, and show increases in eosinophils, T_H2  cells and cytokines, increased mucus secretion in the lung and elevated serum IgE, suggesting a prominent role for the immune system and T cells in the pathology of this disease.  The tyrosine kinase ITK represents a class of enzymes that are tractable to pharmaceutical intervention, and has been implicated in both the activation of naїve T cells as well as in the potential differentiation of T_H2 cells and production of Interleukins IL-4, IL-5 and IL-13.  We hypothesize that if ITK regulates the activation of T cell, the development of T_H2 cells and the production of T_H2 type cytokines, it may logically contribute to the pathological conditions that favor the development of asthma.  Using transgenic inducible mice along with mice lacking ITK we are therefore investigating the role of ITK in the development of allergic asthma in this murine model.

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