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识别有才华的年轻生物医学科学家，培养他们的研究兴趣和人才，并为他们提供技能，使他们成为能够开发新的，创造性的，有效的方法诊断，预防和治疗动脉粥样硬化和血管疾病的高产生物医学科学家。 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养博士前学生和博士后研究员：1）结构生物学部分将侧重于通过现代方法，包括电子晶体学，X射线晶体学和多维NMR，阐明参与脂质转运和代谢的生物分子的结构。 2）生化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。 适用的技术包括蛋白质测序，稳定同位素周转方法，等离子体共振光谱。 3)细胞生物学/分子生物学部分将涉及白细胞粘附、脂肪细胞脂质生物合成、细胞因子引起的心肌细胞改变和血小板与内皮细胞结合的研究。 这些研究将利用基因敲除和转移在小鼠中建立的脂质紊乱，糖尿病和肥胖症的模型。 这一部分也将为理解SMC增殖的基础以及特定基因如何被血流和切应力诱导提供方向。 4)一个新的临床转化部分将包括：i）通过MRI定位和定量动脉粥样硬化病变的新算法的实施，以及它们用于监测脂质改变干预的功效; ii）可溶性TNF受体拮抗剂的临床试验，其显示逆转TNF在肌细胞和动物中的不良作用; iii）在小鼠中显示逆转血脂异常和使糖尿病正常化的新基因治疗策略的人体测试。 这个跨学科，多方面的培训计划包括既建立了具有丰富的培训经验的研究人员，并精心挑选的初级教师谁代表了新兴技术的重要来源和程序连续性的重要环节。

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.