Dr. Michael Myerburg’s Research

Dr. Myerburg’s primary research interests include understanding the role of the epithelial sodium channel (ENaC) in cystic fibrosis and other airway diseases. The goal of this research is to delineate how ENaC activity is regulated and to develop novel therapeutic strategies to mitigate sodium hyperabsorption in the airway. Additionally, he is interested in airway epithelial cell biology, as it relates to mucus clearance from the lung and host defense from inhaled pathogens.

Dr. Myerburg has demonstrated (JBC 06) that ENaC is regulated by the relative balance between membrane tethered proteases, which activate the channel, and soluble protease inhibitors that are present in the airway surface liquid. As shown in the schematic below, this “protease – protease inhibitor balance” establishes an auto-regulatory mechanism to maintain optimal airway surface liquid (ASL) hydration.

Recent work suggests that the balance between channel activating proteases and the endogenous protease inhibitors is altered in cystic fibrosis and related chronic obstructive lung diseases. In particular, we have shown that airway epithelium from cystic fibrosis patients express heightened levels of the protease prostasin (AJP 08). Due to excessive protease activity, ENaC becomes overactive, causing dehydration of the ASL and imparing mucus clearance.

To study the role of proteases in the physiological regulation of sodium and water absorption in the airway, our lab uses primary human airway epithelium that is cultured from excess pathological tissue following lung transplantation. These primary airway cultures develop into mucus producing layers, with prominent cilia, as shown here. Using this model system, we are able to measure mucus transport, ASL volume and absorption, ciliary beat frequency, and short-circuit current.

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