Michael H. Koval, PhD


Department of Cell Biology


Department of Pulmonary, Allergy and Critical Care Medicine

Office: 235 Whitehead Bldg

Email: mhkoval@emory.edu

Office Location:

Mailing Address:

Emory University - Department of Cell Biology

615 Michael St, 1941-001-1AC

Atlanta, GA 30322

Additional Websites

Research Focus

The lung provides a barrier that enables the exchange of oxygen and carbon dioxide between the atmosphere and bloodstream. The part of the barrier which faces the atmosphere (airspace) is covered by epithelial cells with different characteristics, depending upon the location in the lung. The terminal airspace (alveolus), where gas exchange occurs is covered by a layer of cells collectively known as the alveolar epithelium. Cell-cell contacts between alveolar epithelial cells contain distinct elements which contribute to their function. These include tight junctions and gap junctions.

Tight junctions are the primary mechanism that regulates whether the epithelium is tight or leaky. This is due to proteins in the claudins claudin-family that form a seal to both restrict paracellular diffusion and permit specific transport of ions between cells across the epithelial barrier. There are nearly twenty different claudins, and cells simultaneously express several claudins. However, the mechanisms that regulate claudin intermixing are poorly understood at present. Also, it is not know how cells use multiple claudins to regulate epithelial barrier function. A primary goal of my laboratory is to use molecular and cell biological approaches to define roles for different claudins in normal lung barrier function and in pathologic conditions such as acute respiratory distress syndrome (ARDS). A long term goal is to develop methods to augment alveolar barrier function as a means to improve the outcome of patients with ARDS and other forms of lung injury.

Gap junctions consist of channels which interconnect cells in a tissue. This enables the direct transfer of small signaling molecules and metabolites between adjacent cells. There are almost two dozen different gap junction proteins (called connexins) and cells regulate the specificity of intercellular communication by expressing different connexins. The mechanisms which regulate the assembly of connexins into gap junction channels remain poorly understood. In contrast to most transmembrane protein complexes, connexins oligomerize after exit from the endoplasmic reticulum (ER) in different aspects of the Golgi apparatus. This suggests that a novel post-ER mechanism for the control of protein assembly may exist. We have recently employed a system using connexins fused to ER retention/retrieval motifs to trap assembly intermediates and to identify key steps in connexin-specific assembly pathways. One goal of the lab is to identify chaperones that participate in this process, using ER-retained connexins as "bait" to bind potential chaperones. We are also identifying connexin domains that control sorting and gap junction channel assembly, using fluorescence microscopy to examine the behavior of transfected mutant connexin constructs containing domains from multiple connexins. Finally, we are currently developing cell culture and animal models where gap junctional communication is disrupted to define roles for gap junctional communication in lung function and disease.