Investigation of Sickle Cell Adhesion

镰状细胞粘附的研究

• 批准号: 7060349
• 负责人: GILDA A. BARABINO
• 金额: $ 14.12万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060349
• 关键词: animal tissue; biophysics; blood vessel occlusion; cell adhesion; cell adhesion molecules; cell cell interaction; cell surface receptors; clinical research; erythrocytes; human subject; intermolecular interaction; molecular pathology; patient oriented research; receptor expression; shear stress; sickle cell anemia; thrombospondins; tissue /cell culture; training; vascular endothelium

DESCRIPTION (provided by applicant): This proposal outlines a three-year research career development program that will enable the principal investigator to further develop a research career after a period in administration. The PI is a chemical engineering faculty member with biomedical research interests who will benefit from an expansion of research skills and adeptness in this area. A multi-faceted research project on sickle cell adhesion forms the core of the program that brings together eminent experts who will work closely with the PI. Mentor, David Golan, M.D., Ph.D. of Harvard Medical School (HMS) is an expert in bipophysical and imaging techniques, red cell membranes, and sickle cell disease, and has trained over twenty physicians and researchers. Collaborator, D. K. Kaul, Ph.D. of Albert Einstein College of Medicine (AECM) is an expert in sickle cell investigations involving ex vivo animal models, and collaborator, Ulrich von Andrian, M.D., Ph.D. of Harvard Medical School is an expert in studies using intravital microscopy models. It is widely understood that the pathophysiology of vaso-occlusion in sickle cell disease is complex and muti-factorial, and that its treatment will require therapeutic approaches that address mutiple factors. The abnormal adhesion of sickle red blood cells to the vascular endothelium may participate in the initiation of vaso-occlusion, and may occur by multiple mechanisms. The proposed project will apply a muti-pronged approach to the investigation of sickle cell adhesion mechanisms and potential therapeutic agents. We will use state-of-the-art biophysical tools to quantify the basis for sickle cell adhesion at the level of individual adhesion molecules and predict the strength of adhesion. The predictions will be tested in complementary model systems. Experiments will be carried out in the laboratories of the PI and those of the mentor and collaborators. The outstanding research environments of the Department of Biological Chemistry and Molecular Pharmacology, HMS (Golan), The Department of Medicine, AECOM (Kaul), and the Center for Blood Research, HMS (von Andrian) provide an excellent setting for the PI to gain the expertise and research skills that will allow maximal career development.

描述（由申请人提供）： 该提案概述了一项为期三年的研究职业发展计划，该计划将使首席研究员能够在行政管理一段时间后进一步发展研究职业。 PI 是一位对生物医学研究感兴趣的化学工程教员，他将受益于该领域研究技能和熟练程度的扩展。关于镰状细胞粘附的多方面研究项目构成了该项目的核心，该项目汇集了与 PI 密切合作的杰出专家。导师 David Golan，医学博士、哲学博士哈佛医学院 (HMS) 的博士是双物理和成像技术、红细胞膜和镰状细胞病方面的专家，并培训了 20 多名医生和研究人员。合作者，D.K. Kaul，博士阿尔伯特·爱因斯坦医学院 (AECM) 的博士是涉及离体动物模型的镰状细胞研究方面的专家，其合作者 Ulrich von Andrian 医学博士、哲学博士哈佛医学院的教授是使用活体显微镜模型进行研究的专家。人们普遍认为，镰状细胞病血管闭塞的病理生理学是复杂的、多因素的，其治疗需要针对多种因素的治疗方法。镰状红细胞与血管内皮的异常粘附可能参与血管闭塞的启动，并且可能通过多种机制发生。拟议的项目将采用多管齐下的方法来研究镰状细胞粘附机制和潜在的治疗药物。我们将使用最先进的生物物理工具在单个粘附分子水平上量化镰状细胞粘附的基础并预测粘附强度。这些预测将在互补模型系统中进行测试。实验将在PI以及导师和合作者的实验室中进行。 HMS（戈兰）生物化学和分子药理学系、AECOM（考尔）医学系和 HMS（冯·安德里安）血液研究中心的出色研究环境为 PI 获得知识提供了绝佳的环境能够实现最大职业发展的专业知识和研究技能。