My long-term goal as a physician scientist is to determine the etiology and pathogenesis of Kawasaki Disease (KD). For the past several years, I have had protected time for research training through a K08 award, which will be completed as of August 2000. This grant has allowed me to develop as a physician scientist and obtain experimental data which led to my recent success in obtaining R01 funding. To assure protected time for research, additional salary support through the K02 is needed. New data demonstrating that the IgA response in KD is oligoclonal has led to an expansion of aim 1 of my ongoing R01 grant. My hypothesis is that synthetic antibodies derived from the oligoclonal IgA response in KD vascular tissue will be useful in identifying antigens important in KD pathogenesis. This proposal will strengthen and develop my research program by allowing me to focus on the preparation of synthetic KD antibodies and their use as tools to detect important antigen-antibody interactions in KD. I plan to: 1) Generate synthetic antibodies and determine if they recognize antigens in KD tissues, 2) Clone the KD-specific antigen by screening KD tissue cDNA libraries with synthetic antibodies, and 3) Determine whether the antigen is consistently identified in KD but not control patients. Significant preliminary data demonstrating binding of one synthetic antibody to KD but not control tissues attests to the feasibility of this approach to identify antigens important in KD pathogenesis. As part of my development as an independent investigator, I will have the opportunity to interact with the members of the Department of Microbiology and Immunology at Northwestern, the Interdepartmental Immunobiology Center, investigators in the Children's Memorial Hospital Center for Kawasaki Disease, and vascular biology investigators in the Departments of Pediatrics and Pathology. These interactions will take the form of seminar series, journal clubs, laboratory meetings, and informal discussions. Also, an ethics curriculum is outlined in the application. These plans will provide me with opportunities for enhanced career development by acquisition of new research skills, and will be fostered by the strong interdisciplinary research environment at Northwestern.
