Defining the Mechanisms by Which Plateletes Regulate Angiogenesis

定义血小板调节血管生成的机制

• 批准号: 7919950
• 负责人: Elisabeth M Battinelli
• 金额: $ 13.78万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919950
• 关键词: Advisory Committees; Affect; Aftercare; Agonist; Alpha Granule; Ants; Basic Science; Biology; Blood Platelets; Blood Vessels; Clinical; Coagulation Process; Development Plans; Equilibrium; Fellowship; Grant; Hematology; Hemostatic function; Hospitals; Human; Inflammation; Instruction; Internal Medicine; Malignant Neoplasms; Megakaryocytes; Mentors; Modeling; Multivesicular Body; Myelopoiesis; PAWR gene; Pathologic Processes; Patients; Peptide Hydrolases; Physiological; Platelet Activation; Population; Principal Investigator; Process; Proteins; Regulation; Research; Research Personnel; Residencies; Role; Sorting - Cell Movement; Stimulus; Thrombosis; Woman; Wound Healing; abstracting; angiogenesis; career; career development; genetic regulatory protein; interest; numb protein; oncology; programs; receptor; response; skills; tumor growth

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)

描述（由申请人提供）：该提案需要一项为期5年的职业发展计划，以实现血液学学术职业。原则研究者已经完成了内科和血液学/肿瘤学奖学金的居住，现在通过基础科学和翻译方面的项目扩大了她的研究技能。该项目是血小板生物学和血管生成领域的整合。约瑟夫·伊塔利亚诺（Joseph Italiano）博士和南希·伯林纳（Nancy Berliner）博士将担任首席研究员的联合委员会。 Italiano博士是巨核细胞和血小板生物学领域的知名领导者。为了增强该计划的学术指导方面，杨百翰和妇女医院血液学系主任南希·伯林纳博士（BWH）将担任联合会员。除了担任导演的角色外，她还拥有长期的专业知识，并指导了大量的年轻调查员。此外，主要研究人员还组建了一个具有多样化的科学和临床利益的咨询委员会，以提供科学和学术职业建议。该项目将集中于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到药理学和形态上不同的α颗粒种群中，然后在血小板激活后易受差异调节。该建议将需要建立α颗粒中血管生成调节蛋白的组织，并了解差异释放的机制。血小板颗粒内的血管生成平衡也将在患有抗血管生成疗法的患者中进行研究。具体目的是：1。定义血管生成调节蛋白如何隔离并储存在血小板中； 2。研究这些蛋白质经历差异释放的机制；和3。研究血小板在抗血管生成疗法的储存，递送和功能中的作用。相关性（请参阅说明）：已知血小板在生长的血管生长血管中携带许多重要的蛋白质。在这笔赠款中，我们试图确定血小板如何组织蛋白质，调节血管生成以及这些过程在恶性肿瘤患者中如何有所不同，其中血管生成对肿瘤生长具有重要作用。 （抽象的结尾）