CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN ANGIOGENESIS

血管生成卓越生物医学研究中心

• 批准号: 6263277
• 负责人: THOMAS MACIAG
• 金额: $ 189.45万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263277
• 关键词: angiogenesis; fibroblast growth factor; vascular endothelium

Angiogenesis is the formation of new blood vessels from existing structures and is involved in the regulation of wound repair and the pathobiology of numerous disease states including solid tumor growth. Because angiogenesis is regulated by a complex interaction of receptor mediated signals modified by the activities of growth factors, cytokines, proteinases, lipid and components of the extracellular matrix, it sis important for institutions with a focus on angiogenesis to include experimental programs in these and other areas such as mechanisms and intracellular traffick. As a result, this application requests support from the IDeA Program to establish a COBRE in Angiogenesis and involves the collaborative interests of a group of four new (non-R01 funded) and two established investigators at the newly formed (1998) Center for Molecular Medicine at the Maine Medical Center. The theme focuses on Signaling Paradigms in Angiogenesis as a result of the long term research interests of the Program's PI in the biology of the endothelial cell at the cellular and molecular level and the institutional commitment to support a program in Angiogenesis. The motives for this application include the use of this award to (i) support promising young independent investigators in this field, (ii) expand existing institution resources to create a larger critical mass of mechanism-oriented junior and senior investigators in this area, investigator needs and (iv) provide resources requisite for the establishment of an internationally recognized non-profit research institution in the broad area of mechanistic Vascular Biology. The application is comprised of five projects which were chosen in the field of angiogenesis and the areas of interest include the mechanisms of (i) cooperativity between FGF and Jagged 1 signaling in the regulation of chord formation and in the regulation of a stable collateral circulatory system following ischemic heart damage, (ii) the antagonism of FGFR signaling and the regulation of branching by Sprouty, (iii) inflammatory- mediated release of FGF2 as a covalent complex with plasminogen fragments in vivo, (iv) the TGFbeta-receptor-associated protein, endoglin, to mediate arteriovenous malformations and (v) Twist as a transcriptional mediator of tubulogenesis. Program expansion by 2001 will include the recruitment of six investigators with genetic, cellular, and molecular signaling expertise mediated by (i) proteinases and their inhibitors, (ii) extracellular matrix, (iii) cadherins, (iv) VEGF in lymphogenesis and angiogenesis, (v) G-protein-coupled receptors and (vi) intracellular trafficking but the resources from this award will only be used for Program expansion in areas (i) and (ii). It is anticipated that this award will not only enable the Ctr. for Mol. Med. to achieve its goal at a more rapid and efficient rate but the insight derived from these investigators may significantly impact the fields of Angiogenesis and Vascular Biology.

血管生成是从现有结构形成新血管，并参与伤口修复的调节和包括实体瘤生长在内的多种疾病状态的病理学。由于血管生成是由受体介导的信号的复杂相互作用调节的，而受体介导的信号又受生长因子、细胞因子、蛋白酶、脂质和细胞外基质成分的活性修饰，因此对于专注于血管生成的机构来说，将这些领域和其他领域（如机制和细胞内运输）的实验项目纳入其中非常重要。因此，本申请请求 IDeA 计划的支持，以建立血管生成方面的 COBRE，并涉及缅因州医学中心新成立（1998 年）分子医学中心的四名新研究人员（非 R01 资助）和两名已建立的研究人员的合作利益。由于该项目的 PI 对细胞和分子水平的内皮细胞生物学的长期研究兴趣以及支持血管生成项目的机构承诺，该主题重点关注血管生成中的信号范式。本次申请的动机包括利用该奖项来（i）支持该领域有前途的年轻独立研究人员，（ii）扩大现有机构资源，以在该领域培养更多以机制为导向的初级和高级研究人员，满足研究人员的需求，以及（iv）为在机械血管生物学广泛领域建立国际公认的非营利研究机构提供必要的资源。该申请由在血管生成领域选择的五个项目组成，感兴趣的领域包括以下机制：(i) FGF 和 Jagged 1 信号传导在调节弦形成和缺血性心脏损伤后稳定侧支循环系统调节中的协同作用，(ii) FGFR 信号传导的拮抗作用和 Sprouty 的分支调节，(iii) 炎症介导的释放 FGF2 作为体内纤溶酶原片段的共价复合物，(iv) TGFbeta 受体相关蛋白、内皮糖蛋白，介导动静脉畸形，以及 (v) Twist 作为肾小管发生的转录介质。到 2001 年，计划扩展将包括招募六名具有遗传、细胞和分子信号专业知识的研究人员，这些专业知识由 (i) 蛋白酶及其抑制剂、(ii) 细胞外基质、(iii) 钙粘蛋白、(iv) 淋巴生成和血管生成中的 VEGF、(v) G 蛋白偶联受体和 (vi) 细胞内贩运介导，但来自该奖项的资源将 仅用于领域 (i) 和 (ii) 的计划扩展。预计该奖项不仅将使 Ctr.对于摩尔。医学。以更快、更有效的速度实现其目标，但这些研究人员的见解可能会对血管生成和血管生物学领域产生重大影响。