Metabolomic analysis of acute stress hyperglycemia in ischemic stroke

缺血性脑卒中急性应激性高血糖的代谢组学分析

基本信息

批准号：
8224628
负责人：
William Taylor Kimberly
金额：
$ 17.88万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8224628
关键词：
Address Adult Blood Glucose Boston Brain Branched-Chain Amino Acids Caring Cause of Death Cerebrovascular Disorders Clinical Development Development Plans Diabetes Mellitus Disease Educational Curriculum Environment Fatigue General Hospitals Glucose Goals Human Hyperglycemia Institution Insulin Resistance Investigation Ischemia Ischemic Stroke Isoleucine Knowledge Leucine Mass Spectrum Analysis Massachusetts Mentors Mentorship Metabolic Metabolic Diseases Metabolic Pathway Metabolism Methods Nervous System Trauma Neurological outcome Neurologist Non-Insulin-Dependent Diabetes Mellitus OGTT Outcome Patients Physiological Play Prevention Process Research Research Personnel Research Proposals Resources Rodent Model Role Science Stroke Structure Surveys Technology Time Transient Ischemic Attack United States Valine acute stress acute stroke base bench to bedside career career development cerebrovascular disability glucose metabolism impaired glucose tolerance indexing innovation metabolic abnormality assessment metabolomics novel novel strategies patient oriented research programs response skills treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Dr. W. Taylor Kimberly is a Neurocritical Care and Stroke Neurologist at Massachusetts General Hospital (MGH), whose goal is to become an independent investigator with expertise in metabolomics, insulin resistance and to define its contribution to stroke and other cerebrovascular diseases. His career development plan leverages the resources of a world-class environment by bringing together an outstanding team of investigators centered at a leading academic institution in Boston, Massachusetts General Hospital. Dr. Kimberly has already obtained preliminary results demonstrating the feasibility of research plan that uses a novel metabolomic platform that can analyze more than 300 key metabolites at the same time. Under the mentorship of Dr. Robert Gerszten, and co-Mentors Dr. Greg Sorensen and Dr. Jose Florez, Dr. Kimberly proposes: 1) To determine whether branched chain amino acids are altered in the setting of stroke, 2) To determine whether hyperglycemia of stroke influences the way branched chain amino acids (valine, isoleucine and leucine) are altered, and 3) To prospectively investigate whether glucose metabolism and branched chain amino acid alterations will predict neurological outcomes. The overall goal is to elucidate the mechanisms that underlie hyperglycemia in acute stroke and to determine how this leads to worse neurological outcomes. Bringing together cutting-edge technology and a team with relevant expertise, this project will open new avenues for treatment in stroke. This well-defined patient-oriented research proposal, in concert with mentorship and a structured didactic curriculum, will provide Dr. Kimberly with the skills that are essential for him to develop an independent career in cerebrovascular research at the cutting edge of science. PUBLIC HEALTH RELEVANCE: Despite modern advances in prevention and treatment, stroke remains the leading cause of adult disability and the second leading cause of death worldwide. Dr. Kimberly's proposed career development plan has outstanding potential to advance our knowledge of the interaction between metabolism and ischemic stroke, which is a crucial step towards the discovery of novel treatment strategies.

描述（由申请人提供）：W. Taylor Kimberly 博士是马萨诸塞州总医院 (MGH) 的神经重症监护和中风神经科医生，其目标是成为一名在代谢组学、胰岛素抵抗方面拥有专业知识的独立研究者，并确定其对中风的影响以及其他脑血管疾病。他的职业发展计划利用了世界一流环境的资源，汇集了以波士顿领先学术机构马萨诸塞州总医院为中心的优秀研究团队。 Kimberly博士已经获得了初步结果，证明了使用新型代谢组学平台的研究计划的可行性，该平台可以同时分析300多种关键代谢物。在 Robert Gerszten 博士以及共同导师 Greg Sorensen 博士和 Jose Florez 博士的指导下，Kimberly 博士建议：1) 确定支链氨基酸在中风情况下是否发生改变，2) 确定支链氨基酸是否在中风情况下发生改变中风的高血糖影响支链氨基酸（缬氨酸、异亮氨酸和亮氨酸）的改变方式，3) 前瞻性研究葡萄糖代谢和支链氨基酸改变是否将预测神经系统结果。总体目标是阐明急性中风高血糖的机制，并确定其如何导致更糟糕的神经系统结果。该项目汇集了尖端技术和具有相关专业知识的团队，将为中风治疗开辟新途径。这项明确的以患者为导向的研究计划，与指导和结构化的教学课程相结合，将为 Kimberly 博士提供在科学前沿的脑血管研究中发展独立职业所必需的技能。公共卫生相关性：尽管现代在预防和治疗方面取得了进步，中风仍然是成人残疾的主要原因，也是全球第二大死亡原因。金伯利博士提出的职业发展计划具有巨大的潜力，可以增进我们对新陈代谢和缺血性中风之间相互作用的了解，这是发现新治疗策略的关键一步。