Metabolomic analysis of acute stress hyperglycemia in ischemic stroke

描述（由申请者提供）：W. Taylor Kimberly博士是马萨诸塞州总医院（MGH）的神经危重症护理和中风神经科医生，他的目标是成为一名独立的研究者，在代谢组学、胰岛素抵抗方面具有专业知识，并确定其对中风和其他脑血管疾病的贡献。他的职业发展计划利用了世界级环境的资源，在波士顿马萨诸塞州总医院的领先学术机构汇集了一支优秀的研究团队。金伯利博士已经获得了初步结果，证明了研究计划的可行性，该计划使用一种新的代谢组学平台，可以同时分析300多种关键代谢物。在Robert Gerszten博士、Greg Sorensen博士和Jose Florez博士的指导下，Kimberly博士提出：1)确定支链氨基酸是否在中风的情况下发生改变，2)确定卒中的高血糖是否会影响支链氨基酸（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的改变是否会预测神经预后。总体目标是阐明急性卒中中高血糖的机制，并确定高血糖如何导致更糟糕的神经系统预后。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的途径。这项明确的以患者为导向的研究计划，加上指导和结构化的教学课程，将为金伯利博士提供必要的技能，使他能够在科学前沿的脑血管研究领域独立发展。

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.