Core B: Analytics for Mucolytics Core

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Abstract The mucus layer lining the respiratory tract acts as the body's first line of defense against inhaled pathogens and airborne particulate matter. Proper trapping of particulates and clearance from the lung is therefore critical to maintaining pulmonary function. The goal of the Analytics for Mucolytics Core is to use the biochemical and biophysical experimental expertise of its investigators to develop biomarkers of the effect of disease and therapeutic interventions. These biomarkers will be derived from a multidisciplinary, basic scientific characterization of pulmonary mucus samples collected by the four Projects of this tPPG. The motivation for the Analytics for Mucolytics Core is rooted in the goals of this tPPG and can be summarize as such: 1) elucidate the biological basis of muco-obstructive airway diseases, 2) investigate the polymeric, physical basis of the underlying pathology of these diseases, and 3) test the efficacy of mucolytic and hydration therapies. The core will be further governed by the hypothesis that muco-obstructive diseases such as cystic fibrosis and asthma cause pathological alterations to the biochemical composition of respiratory mucus, resulting in a hyper-concentrated mucus layer. The thickening of airway mucus leads to altered biophysical properties that impede mucociliary clearance and ultimately cause a decline in lung function. The therapeutic goal of this tPPG is to develop clinical treatments that restore pathological mucus to its proper biochemical and biophysical state, and thereby restore its normal physiological function. The Analytics for Mucolytics Core will draw on the talents of a diverse team of researchers within the Marsico Lung Institute who have developed and implemented novel, state-of-the-art experimental capabilities for the characterization of the biochemical and biophysical properties of mucus. Core PI, Dr. Mehmet Kesimer, is a world-recognized leader of mucin biochemistry and how changes to the biochemical composition of mucus correlate to changes in pulmonary function. Dr. Ehre and Dr. Livraghi-Butrico add a wealth of experience in biochemical imaging techniques of mucins and mucus, and relating these measurements to pulmonary function in animal model systems and human subjects. Dr. Hill and Dr. Button are experts in the biophysical characterization of the wide range of mucus sample types the Analytics for Mucolytics Core will analyze from the diverse projects that make up this tPPG. Dr. Hill and Dr. Button are leaders in relating mucus biophysical properties to physiological changes. Together, this diverse, multidisciplinary team brings a unique, unrivaled set of skills that the core will employ to develop biomarkers of pulmonary physiology. Further, the proven track record of the core investigators working in concert with clinicians will insure that the basic science approach of the core will be tightly focused on developing biomarkers that are the best descriptors of the physiological effect of disease and assess efficacy of therapeutic compounds to restore normal lung function.