The general and long-term goal of my laboratory is to study autoantibody-mediated skin diseases in order to further our understanding not only of the pathophysiology of these diseases but also of the structure and function of normal epidermis. Specifically, we have found that autoantibodies from these patients, who develop blistering diseases due to defects in epidermal cell adhesion, are directed against adhesion molecules. We are characterizing, by immunochemical and molecular biologic means, the antigens defined by three of these diseases: bullous pemphigoid (BP), pemphigus vulgaris (PV), and pemphigus foliaceus (PF). This then allows us to study their cell biologic function. BP antigen is a component of the hemidesmosome, a basal-cell substrate adhesion junction. Using a polymerase chain reaction technique called rapid amplification of cDNA ends, we have finished cloning cDNA with the full length coding sequence for this molecule. Analysis of its deduced amino acid sequence indicates that BP antigen is a totally intracellular protein that has marked amino acid and structural homology with desmoplakin I, a desmosome plaque protein, and with plectin, a keratin-associated protein. We have also cloned cDNA with the full length coding sequence for PV antigen. The deduced amino acid sequence of this antigen indicates that it is in the cadherin family of calcium-dependent cell adhesion molecules and is closely related to the PF antigen. PV patients have antibodies against the amino-terminal domain of this molecule, an area thought to be important in its adhesion function, and these antibodies can cause loss of adhesion of epidermal cells in an animal model of disease. In order to study the biological function of PV antigen, we have transfected eukaryotic cells with cDNA the encodes its extracellular domains as well as mutated cDNA that encodes a truncated extracellular domain and a normal cytoplasmic domain.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB003667-10
Application #
3751993
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code