The Lewis' Lab crew, 2002-2003

(L to R) Scott Rudzinski, Jani Lewis (PI), Tracy Teo, Corinne DePersis, Rick Hoffmaster

Research Focus: The cadherin/catenin based cell adhesion system.

The focus of my lab is the cadherin/catenin based cell adhesion system. Presently I am running two projects, one dealing with hormonal regulation of the cadherins in various squamous epithelial cell lines, the other dealing with the regulation of the cadherin/catenin complex in lens formation. Cadherins are transmembrane glycoproteins which connect the actin cytoskeleton of adjacent cells via intracellular proteins known as the catenins.1 Together the cadherin/catenin complex of adjacent cells forms a connective complex known as the adherens junction. This junction appears to be necessary not only to the formation of other types of cellular junctions but also to tissue formation.2

Hormonal regulation of cadherin expression in squamous epithelial cell lines. We have found that the vulvar carcinoma cell line, A431, is particularly sensitive to the glucocorticoid analogue, dexamethasone.3 When treated with dexamethasone, these cells downregulate both E- and P-cadherin within 7-10 days of continuous application. This downregulation is an irreversible phenomenon. Our goal is to decipher the mechanism by which this downregulation occurs. Downregulation of cadherins by other hormones such as progesterone or estrogen does not occur in these cells.

Formation and makeup of the cadherin/catenin complex during lens formation. Formation of the lens occurs very early in embryonic development. Unlike most tissues, lens cells never turn over, ie, the lens cells you have at birth stay with you for life. In most other tissues, the cadherin/catenin complex is continually recycled as the cells move within that tissue, differentiate and, in some cases, die off. It is unclear, therefore, how the cadherin/catenin complex stabilizes in the oldest cells of the lens.4 The goal of this project is to analyze the molecular makeup and stability of adherens junctions during lens development and maturation.

References

1. Lewis, J. E. 2002. The role of cadherins in tumor suppression. Mod. Aspects Immunobiol. 2:126-129.

2. Lewis, J. E., Jensen, P. J. and Wheelock, M. J. 1994. Cadherin function is required for human keratinocytes to assemble desmosomes and stratify in response to calcium. J. Invest. Derm. 102:870-877.

3. Lewis, J. E., Wahl, J. K., Sass, K. M., Jensen, P. J., Johnson, K. R., and Wheelock, M. J. 1997. Cross-talk between adherens junctions and desmosomes depends on plakoglobin. J. Cell Biol. 136:919-934.

4. Bagchi, M., Katar, J., Lewis, J., and Maisel, H. 2002. Associated Proteins of Lens Adherens Junction. J. Cell. Biochem. 86: 700-703.