Atherosclerosis and Vascular Biology Training Center

描述(由申请人提供)： 该培训计划的总体目标是寻找有才华的年轻生物医学科学家，培养他们的研究兴趣和才华，并为他们提供技能，使他们能够成为高生产率的生物医学科学家，能够开发新的、创造性的、有效的方法来诊断、预防和治疗动脉粥样硬化和血管疾病。为了实现这一目标，已经开发了一个多学科计划，在四个广泛的领域培训博士后学生和博士后研究员：1)结构生物学部分将专注于通过电子结晶学、X射线结晶学和多维核磁共振等现代方法阐明与脂质运输和代谢有关的生物分子的结构。2)生物化学部分将强调脂蛋白氧化、脂蛋白代谢和血小板蛋白相互作用的机制。可应用的技术包括蛋白质测序、稳定同位素周转方法学和等离子体共振光谱学。3)细胞生物学/分子生物学部分将涉及白细胞黏附、脂肪细胞脂肪生物合成、细胞因子对心脏细胞的改变以及血小板与内皮细胞的结合的研究。这些研究将利用小鼠的基因敲除和转移来建立脂质紊乱、糖尿病和肥胖症的模型。这一部分还将为理解SMC增殖的基础以及血流和切应力如何诱导特定基因提供方向。4)一个新的临床翻译部分将包括i)通过核磁共振对动脉粥样硬化病变进行定位和量化的新算法的实施，以及它们用于监测调脂干预措施的有效性；ii)临床测试可溶性肿瘤坏死因子受体拮抗剂，证明可以逆转肿瘤坏死因子对心肌细胞和动物的不良影响；iii)对新的基因治疗策略进行人体测试，这些策略被证明可以逆转小鼠的血脂紊乱和糖尿病正常化。这一跨学科、多层面的培训计划既包括具有丰富培训经验的资深研究人员，也包括精心挑选的初级教员，他们代表着新兴技术的重要来源，也是项目连续性的重要环节。

DESCRIPTION (provided by applicant): The overall goal of this training program is to identify talented, young biomedical scientists, to nurture their research interests and talents, and to provide them with the skills that will enable them to be highly productive biomedical scientists capable of developing new, creative, and effective approaches for the diagnosis, prevention, and treatment of atherosclerosis and vascular diseases. To achieve this goal, a multidisciplinary program has been developed to train predoctoral students and postdoctoral fellows in four broad areas: 1) A structural biology component will focus on elucidating the structure of biomolecules involved in lipid transport and metabolism by modern methods including electron crystallography, x-ray crystallography, and multi-dimensional NMR. 2 ) A biochemistry component will emphasize mechanisms of lipoprotein oxidation, lipoprotein metabolism, and interaction of platelet proteins. Applicable techniques include protein sequencing, stable isotope turnover methodology, and plasmon resonance spectroscopy. 3) A cell biology/molecular biology component will involve studies of leukocyte adhesion, adipocyte lipid biosynthesis, cardiocyte alterations by cytokines, and platelet binding to endothelium. These studies will utilize gene knockout and transfer in mice established as models for lipid disorders, diabetes, and obesity. This component will also provide direction in understanding the basis of SMC proliferation and how specific genes are induced by blood flow and shear stress. 4) A new clinical translational component will include i) implementation of new algorithms for localization and quantification of atherosclerotic lesions by MRI, and their use for monitoring the efficacy of lipid altering interventions; ii) clinical testing of soluble TNF receptor antagonists shown to reverse undesirable effects of TNF in myocytes and animals; iii) human testing of novel gene therapy strategies shown to reverse dyslipidemia and normalize diabetes mellitus in mice. This interdisciplinary, multi-faceted training plan includes both established investigators with extensive training experience, and carefully selected junior faculty who represent a vital source of newly emerging technology and an important link in program continuity.