Pathophysiology of anti-B2GPI Antibodies in APS

描述（由申请人提供）：在申请指导研究科学家发展奖时，首席研究员要求在北卡罗来纳大学教堂山分校病理学教授Susan Lord博士和医学副教授Robert Roubey博士的监督下，支持一个强化培训计划。本提案的目的是加强申请人在凝血和细胞生物学的生化基础的科学背景。如果获得资助，该奖项将促进申请人在止血和血栓形成领域发展独立科学研究事业的长期目标。候选人和她的导师制定了一个职业发展计划，其中包括：a)保证100%的研究时间；b)一个培训计划，使候选人接触到生物化学、生物学和医学的新科学研究领域；c)研究生水平的学习，以加强实验室经验。

DESCRIPTION (provided by applicant): In applying for the Mentored Research Scientist Development Award, the principal investigator is requesting support for an intensive program of training under the supervision of Dr. Susan Lord, Professor of Pathology, and Dr. Robert Roubey, Associate Professor of Medicine, at the University of North Carolina at Chapel Hill. The objectives of this proposal are designed to strengthen the applicant's scientific background in the biochemical basis of coagulation and cell biology. The award, if funded, will facilitate the long-term goals of the applicant in developing an independent scientific research career in the field of hemostasis and thrombosis. The Candidate and her mentors have developed a career development plan which includes: a) assurance of protected research time of 100 %, b) a training program exposing the Candidate to new areas of scientific investigation in biochemistry, biology and medicine, and c) graduate level studies to reinforce the laboratory experience. The studies proposed in this application will extend the applicant's previous work in hemostasis and thrombosis research. The prevalence of venous thrombosis associated with the primary Antiphospholipid Syndrome (APS) may be as high as 0.3 to 1% of the general population, possibly making APS one of the most common autoimmune diseases. It is hypothesized that antibodies against the plasma protein B2GPI are involved in the pathogenesis of this disease. Annexin A2 has recently been identified as the cellular receptor for B2GPI. To study the biological and cellular interactions of anti-B2GPI antibodies, the following specific aims will be addressed: 1) Determining whether annexin A2 mediates anti-B2GPI antibody-regulated expression of TF activity, 2) Determining whether annexin A2-mediated fibrinolytic activity is regulated by B2GPI or B2GPI/anti-B2GPI, and 3) Determining whether APS autoantibodies alter the structure and fibrinolytic susceptibility of the fibrin clot. It is expected that these proposed studies will contribute to a fundamental understanding of pathogenic mechanisms for thrombosis in APS and lead to future investigations addressing therapeutic interventions in APS.