My N. Helms
Assistant Professor of Physiology
Ph.D., Dartmouth Medical School, 2003
Affiliations: Emory Center for Cell and Molecular SignalingEmory Center for Respiratory Health
Emory Division of Digestive Diseases
American Physiological Society
Research Interests:
Needless to say, the lung is very important. Within the lungs, inspired air passes from the bronchioles down into the alveoli (or air sacs) where inspired oxygen and carbon dioxide exchanges across the alveolar epithelium and the capillary endothelium. This normal exchange of gas can occur effectively in the healthy lung, —so long as the air and breathing space is kept clear and dry. If there is too much fluid in the alveoli, then gas exchange will be compromised as fluid-filled air sacs lose compliance and collapse. On the other hand, significantly reduced fluid levels in the alveoli will limit the ability of ciliated cells to sweep out foreign matter, and thereby increases the lung’s susceptibility to infection and compromises gas exchange. Because the alveolar fluid levels must be maintained at precise volumes, it is important to better understand the mechanisms which regulate solute transport in the alveoli.
Structurally, it is clear that alveolar type 1 and type 2 cells comprise the alveolar epithelium, and play a central role in maintaining effective gas exchange. However, it has only recently been appreciated that these cells play an integral role in regulating lung fluid balance. New findings, stemming largely from our significant advances in understanding the biophysical properties of type 1 and type 2 cells, reveal that both cells types express functional epithelial sodium channels (ENaC) capable of counterbalancing fluid gained from passive secretion of solute from the vasculature into the airspace. Furthermore, our preliminary results suggest that the oxidative microenvironment of the alveoli may influence the rate of salt and water transport across type 1 and type 2 cells. Our studies suggest that O2- anions may have a permissive effect on Na reabsorption, and that model type 1 cells may produce more O2- anions than type 2 cells. In light of new evidence that shows that normal cells can regulate their redox state through Rac1 control of NADPH oxidase, we investigate the effect of redox signaling on lung epithelial sodium channels in order to gain a better understanding of how the alveoli maintains appropriate fluid levels. Using novel model systems developed in our laboratory, electrophysiological measurements, as well as standard biochemical assays; we can uniquely study all the cells that make up the alveoli. Therefore, we will be able to make novel comparisons between redox signaling and ENaC function in both alveolar type 1 and type 2 cells.
Publications: PubMed search