The Klarlund laboratory is focusing on corneal epithelial wound healing. Defects in corneal epithelial healing can be very serious and may ultimately lead to blindness, and it is therefore clinically highly relevant to study the healing process. The cornea is an attractive experimental model because of the simple structure of the tissue: It consists of only three layers, contains no lymph or blood vessels under normal conditions, and is very accessible for experimental manipulations.

There are many interesting issues in understanding how epithelia respond to wounding. In the cornea, as in most epithelia, wounds are covered amazingly quickly because the cells near the lesions reorganize their motility machinery so they can migrate very quickly. How does this occur? That is how do cells “know” that there is a wound and how is that information processed within the cells?

We are working with a variety of in vitro models for wound healing. One interest is to identify signals that cause epithelial cells to move. Signals could be interaction with the extracellular matrix, mechanical stimulation, and/or soluble factors. Another interest is to understand the intracellular signals that cause epithelial cells to reorganize to become highly motile. We have found that activation of a ligand for the epidermal growth factor receptor is a crucial event, and that this occurs through a lipid signaling system (phospholipase D). However, much is still to be learned about how these signaling systems are integrated. Currently, we are interested in understanding the immediate signals that lead to activation of phosphlipase D, and identifying the targets for the messenger, phosphatidic acid, that is produced by the lipase. Ultimately, an understanding of important signaling pathways should allow rational strategies to develop drugs to promote healing of wounds in the corneal and other epithelia.