The Role of Plasminogen Activator Inhibitor-1 in the Development and Progression of Obesity

纤溶酶原激活剂抑制剂-1 在肥胖发生和进展中的作用

• 批准号: 8984104
• 负责人: Sadiya Sana Khan
• 金额: $ 6.61万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984104
• 关键词: Accounting; Adult; Affect; Age; Amish; Area; Award; Beta Cell; Biology; Blood Vessels; Body Composition; Body Weight decreased; Body fat; Body mass index; Cardiology; Cell physiology; Clinical; Clinical Data; Cohort Studies; Collaborations; Communities; Coronary Arteriosclerosis; Coronary Artery Risk Development in Young Adults Study; Data; Data Analyses; Development; Diet; Disease Outcome; Economics; Epidemic; Epidemiology; Family; Fatty acid glycerol esters; Fellowship; Frameshift Mutation; Genetic; Goals; Grant; Health Care Costs; Hemophilia A; Heterozygote; Homozygote; Human; Indiana; Individual; Insulin Resistance; Internal Medicine; Life; Link; Measures; Mediating; Mentors; Mentorship; Metabolic; Mission; Modeling; Molecular; Morbidity - disease rate; Mus; Mutation; National Research Service Awards; Nonsense Codon; Obesity; Obesity associated disease; Outcome; Overweight; Participant; Pathway interactions; Phenotype; Physicians; Plasma; Plasminogen; Plasminogen Activator Inhibitor 1; Population; Positioning Attribute; Prevalence; Prevention; Primary Prevention; Production; Proteins; Public Health; Publishing; Reporting; Research; Research Infrastructure; Research Methodology; Research Personnel; Research Project Grants; Risk; Risk Factors; Role; Sampling; Scientist; Serine Proteinase Inhibitors; Study models; Symptoms; Testing; Thrombosis; Time; Training; Translational Research; Translations; Triglycerides; United States; United States National Institutes of Health; Universities; Variant; Visceral; Waist-Hip Ratio; Weight Gain; Writing; base; cardiovascular disorder epidemiology; career; clinical investigation; cohort; community living; cost; data management; design; disorder risk; emerging adult; fasting glucose; feeding; follow-up; genetic epidemiology; girls; improved; inhibitor/antagonist; insight; insulin sensitivity; kindred; longitudinal course; loss of function; meetings; member; middle age; mortality; multidisciplinary; novel; pre-clinical; prevent; proband; public health relevance; racial difference; response; sex; skills; small molecule; targeted treatment; trend; young adult

 DESCRIPTION (provided by applicant): The goal of this NRSA individual postdoctoral fellowship is to facilitate Dr. Sadiya Khan's development as an independent physician-scientist and a leader in translational cardiometabolic research, with a focus on molecular mechanisms of obesity and obesity-related diseases. Dr. Khan and her mentors have designed a specific training plan to build upon her background in internal medicine, clinical cardiology training, and basic and clinical investigation, aiming towards launching her career as an independent investigator. Dr. Khan proposes to develop additional skills during the award period through (1) coursework designed to expand her methodological skills; (2) interaction with a multidisciplinary team of sponsors and collaborators, including those in vascular biology and cardiovascular and genetic epidemiology, and (3) a supervised research project. The overall scientific objective of this project is to investigate the role of plasminogen activator inhibitor-1 (PAI- 1), a serine protease inhibitor, in weight gain and obesity through two primary specific aims: (1) To define the longitudinal profile of circulating PAI-1 levels across early adulthood to middle-age and investigate the association with obesity in the Coronary Artery Disease Risk in Young Adults (CARDIA) study; and (2) To characterize the anthropometric and metabolic phenotype of a unique human PAI-1 loss-of-function cohort in the Berne Amish kindred. The project, along with the proposed coursework and mentorship plan, will allow the candidate to become proficient at translational research methodology with a special emphasis on longitudinal cohort studies, data analysis and management, genetic epidemiology, and scientific writing. This project will meet the mission of the National Institutes of Health by enabling the translation of basic discoveries about the causes of obesity through a collaborative research infrastructure with an overarching goal to help reduce the significant public health burden of obesity and obesity-related diseases. Improving the understanding of the molecular mechanisms underlying the development, progression, and complications of obesity is needed to develop new potential targets for treatment and to aid in primordial and primary prevention efforts. Near the end of the award period, Dr. Khan plans to submit a pathway to independence award application or similar grant using the results of the project to further investigate the molecular mechanisms linking obesity and cardiometabolic disease outcomes.

 描述（由申请人提供）：该 NRSA 个人博士后奖学金的目标是促进 Sadiya Khan 博士发展成为一名独立的医师科学家和转化心脏代谢研究的领导者，重点是肥胖和肥胖相关疾病的分子机制Khan 博士和她的导师根据她在内科、临床心脏病学培训以及基础和临床研究的背景，设计了一项具体的培训计划，旨在开启她作为独立研究者的职业生涯。在奖励期间通过以下方式发展额外技能：(1) 旨在扩展她的方法学技能的课程；(2) 与赞助商和合作者的多学科团队互动，包括血管生物学、心血管和遗传流行病学领域的团队，以及 (3) 监督研究该项目的总体科学目标是通过两个主要具体目标研究纤溶酶原激活剂抑制剂-1 (PAI-1)（一种丝氨酸蛋白酶抑制剂）在体重增加和肥胖中的作用：(1) 定义纵向分析成年早期到中年期间的循环 PAI-1 水平，并在年轻人冠状动脉疾病风险 (CARDIA) 研究中调查与肥胖的关系；(2) 描述独特人类的人体测量和代谢表型；伯尔尼阿米什家族的 PAI-1 功能丧失队列 该项目以及拟议的课程作业和指导计划将使候选人精通转化研究方法，特别强调纵向队列研究、数据分析和研究。管理学、遗传学该项目将通过合作研究基础设施转化有关肥胖原因的基本发现，从而履行美国国立卫生研究院的使命，其总体目标是帮助减轻肥胖和肥胖造成的重大公共卫生负担。奖励期即将结束时，需要提高对肥胖发生、进展和并发症的分子机制的了解，以开发新的潜在治疗目标并帮助进行原始和初级预防工作。汗计划提交利用该项目的结果申请独立奖或类似资助的途径，以进一步研究肥胖与心脏代谢疾病结果之间的分子机制。