Defining the Mechanisms by Which Plateletes Regulate Angiogenesis

描述(由申请人提供)：该提案需要一个5年的职业发展计划，以实现在血液学的学术生涯。这位首席研究员已经完成了内科和血液学/肿瘤学研究员的住院医生资格，现在正在通过一个同时包含基础科学和翻译方面的项目来扩展她的研究技能。该项目是血小板生物学和血管生成领域的整合。约瑟夫·意大利亚诺博士和南希·伯林纳博士将担任首席研究员的联合导师。意大利亚诺博士是巨核细胞和血小板生物学领域公认的领导者。为了加强该计划的学术指导，布里格姆妇女医院(BWH)血液科主任南希·伯林纳博士将担任共同导师。除了担任主任外，她还在骨髓造血方面拥有长期的专业知识，并指导了一大批年轻的调查人员。此外，首席调查员还组建了一个具有不同科学和临床兴趣的咨询委员会，提供科学和学术职业建议。该项目将重点研究血小板在血管生成中的作用。最近的证据表明，血小板将血管生成调节蛋白组织成药理上和形态上不同的阿尔法颗粒群体，然后这些α颗粒容易受到对血小板激活的不同调节。这项提议将需要建立阿尔法颗粒中血管生成调节蛋白的组织结构，并了解差异释放的机制。恶性肿瘤患者和接受抗血管生成治疗的患者也将研究血小板颗粒内的血管生成平衡。其具体目的是：1.明确血管生成调节蛋白是如何隔离和储存在血小板中的；2.研究这些蛋白发生差异释放的机制；3.研究血小板在抗血管生成治疗中的储存、输送和功能中的作用。相关性(见说明)：已知血小板携带许多在血管生长过程中重要的蛋白质，称为血管生成。在这项资助中，我们试图确定血小板如何组织蛋白质，调节血管生成，以及在血管生成有助于肿瘤生长的恶性肿瘤患者中，这些过程有何不同。(摘要结束)

DESCRIPTION (provided by applicant): The proposal entails a 5 year career development plan for attaining an academic career in Hematology. The principle investigator has completed both residency in Internal Medicine and Hematology/Oncology Fellowship and now is expanding her research skills through a project with both basic science and translational aspects. The project is an integration of the fields of platelet biology and angiogenesis. Dr. Joseph Italiano and Dr. Nancy Berliner will act as co-mentors for the principal investigator. Dr. Italiano is a well recognized leader in the field of megakaryocyte and platelet biology. To enhance the academic mentoring aspects of the program, Dr. Nancy Berliner, Chair of the Division of Hematology at Brigham and Women's Hospital (BWH) will serve as a co-mentor. In addition to her role as Director, she has a long-term expertise in myelopoiesis and has mentored a large number of young investigators. In addition, the principle investigator has assembled an advisory committee with varied scientific and clinical interests to provide scientific and academic career advice. The project will focus on the role of the platelet in angiogenesis. Recent evidence suggests that platelets organize angiogenic regulatory proteins into pharmacologically and morphologically distinct populations of alpha granules, which are then susceptible to differential regulation upon platelet activation. This proposal will entail establishing the organization of angiogenic regulatory proteins in alpha granules and understanding mechanisms of differential release. The angiogenic balance within platelet granules will also be investigated in patients with malignancy as well as those receiving anti-angiogenic therapies. The specific aims are: 1. To define how angiogenesis regulatory proteins are sequestered and stored in platelets; 2. To investigate the mechanisms by which these proteins undergo differential release; and 3. To investigate the role of the platelet in storage, delivery, and function of ant-angiogenic therapy. RELEVANCE (See instructions): Platelets are known to carry a number of proteins important in the process of growing blood vessels termed angiogenesis. In this grant we try to determine how platelets organize the proteins, regulate angiogenesis, and how these processes differ in patients with malignancy in which angiogenesis is instrumental for tumor growth. (End of Abstract)