Regulation of adipose inflammation and metabolic syndrome by adipsin/factor D

描述（由申请人提供）：本研究计划书概述了布里格姆妇女医院和哈佛医学院心脏病学研究员James C. Lo, m.d., Ph.D.，在丹娜-法伯癌症和哈佛医学院细胞生物学和医学教授Bruce Spiegelman博士的指导下，作为一名独立的首席研究员的五年职业发展计划。Spiegelman博士是美国国家科学院（National Academy of Sciences）院士，也是脂肪生物学和代谢疾病方面的世界级专家。重要的是，Spiegelman博士在指导科学家方面有着良好的记录，有20多名学员担任学术教职。咨询委员会由G¿khan Hotamisligil，医学博士，哈佛大学公共卫生学院教授，Diane Mathis，哈佛医学院教授，和Evan Rosen，医学博士，博士贝斯以色列女执事医疗中心副教授组成，将提供能量稳态，炎症，压力，脂质代谢，脂肪细胞谱系承诺/分化和免疫调节方面的专业知识。罗博士将利用Spiegelman实验室和哈佛医学院周围的世界级环境，包括丹娜-法伯癌症研究所和布里格姆妇女医院来实现提案中的目标。该计划允许罗博士在代谢和炎症性疾病的交叉领域发展专业知识，并过渡到独立研究者。肥胖是心血管疾病的独立危险因素。最近的研究强调了脂肪组织炎症和代谢性疾病之间的密切联系。脂肪炎症驱动代谢综合征的发展。脂素/补体因子D在多种肥胖模型中是一种脂肪特异性免疫因子缺乏。在备选方案中，Adipsin控制限速步骤

DESCRIPTION (provided by applicant): This research proposal outlines a 5-year career development plan for James C. Lo, M.D., Ph.D., cardiology fellow at Brigham and Women's Hospital and Harvard Medical School to achieve independence as a principal investigator under the mentorship of Bruce Spiegelman, Ph.D., Professor of Cell Biology and Medicine at the Dana-Farber Cancer and Harvard Medical School. Dr. Spiegelman is a member of the National Academy of Sciences and a world expert on adipose biology and metabolic diseases. Importantly, Dr. Spiegelman has a strong track record of mentoring scientists with over 20 trainees holding academic faculty positions. An advisory committee composed of G¿khan Hotamisligil, M.D, Ph.D. Professor at the Harvard School of Public Health, Diane Mathis, Ph.D. Professor at Harvard Medical School, and Evan Rosen, M.D., Ph.D. Associate Professor at Beth Israel Deaconess Medical Center will provide expertise on energy homeostasis, inflammation, stress, lipid metabolism, adipocyte lineage commitment/differentiation, and immune regulation. Dr. Lo will take advantage of the world class environment at the Spiegelman lab and surrounding Harvard Medical School campus, including the Dana-Farber Cancer Institute and Brigham and Women's Hospital to achieve the aims in the proposal. This plan allows Dr. Lo to develop expertise at the intersection of metabolic and inflammatory diseases and transition to an independent investigator. Obesity is an independent risk factor for cardiovascular disease. Recent studies have highlighted the intimate link between adipose tissue inflammation and metabolic diseases. Adipose inflammation drives the development of metabolic syndrome. Adipsin/complement factor D is an adipose-specific immune factor deficient in multiple models of obesity. Adipsin controls the rate-limiting step in the alternative complement pathway and generates the anaphylatoxin C3a, a potent immune activator. This places adipsin as a prime candidate to coordinate adipose tissue inflammation and the ensuing metabolic consequences of obesity and inflammation. The major objective of this project is to determine the function of adipsin in the pathogenesis of obesity and diabetes and to test whether adipsin-directed therapy can be an effective treatment for metabolic disease. The investigator will employ adipsin-deficient mice for in vivo metabolic studies, recombinant proteins within the adipsin pathway to dissect the mechanism, and test novel adipsin-directed therapies for treatment of obesity and diabetes.