This application proposes funding with the specific intent of developing an independent research program by the principal investigator. The applicant has received clinical training in the fields of pediatrics and internal medicine and is a board certified internist and pediatrician. She is currently completing subspecialty training in the fields of pediatric rheumatology and adult rheumatology and has pursued her interest in basic science research in the areas of T cell immunology and autoimmune disease. This training is in preparation of an academic career as a rheumatologist/immunologist with a special interest in autoimmune diseases of children and young adults, and their immunopathogenesis. This research proposal examines the role of CD6, a glycoprotein expressed on T lymphocytes, in autoreactivity and in cell-cell interactions, including binding of antigen presenting cells in peripheral blood, T cells. Experiments are also proposed to examine the regulation of CD6. This investigator's previous work on CD6, suggests the existence of a CD6 ligand on antigen presenting cells in peripheral blood on synoviocytes and on keratinocytes. This applicant has demonstrated that anti-CD6 monoclonal antibodies inhibit both antigen specific and autoreactive response of human cloned T lymphocytes, as well as binding of CD6+ cells to not-T cells. This is vitro model of autoreactivity appears to have relevance to human autoimmunity. The applicant is now in a position to develop her own independent research program as a junior faculty member of the Department of Internal Medicine, with continuing connections to the Department of Pediatrics. It is expected that the applicant will be promoted to a tenure track junior faculty position in the Departments of Pediatrics and Internal Medicine during the time of the award. The sponsor, who is the head of the Division of Rheumatology, is committed to contributing protected time and resources to the applicant. Additionally the proposed collaborators have demonstrated expertise in the proposed areas of research and in the training of investigators. The applicant's long term goals are to participate in an academic medical community as a rheumatologist with a combined appointment in both a Department of Pediatrics and Internal Medicine. Furthermore, as a basic scientist she hopes to study areas of basic immunology and molecular genetics in order to advance understanding of autoimmune disease. Eventually, she hopes to provide a basic science laboratory environment for pediatric rheumatology trainees in order to contribute to knowledge in areas relevant to pediatric rheumatic diseases.
