CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN ANGIOGENESIS

血管生成是指从现有的结构中形成新的血管，参与伤口修复的调节和许多疾病状态的病理生物学，包括实体瘤的生长。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，这些信号受到生长因子、细胞因子、蛋白水解酶、脂质和细胞外基质成分的调节，因此，对于专注于血管生成的机构来说，包括这些领域和其他领域的实验计划是很重要的，例如机制和细胞内交通。因此，本申请请求IDEA计划的支持，以建立血管生成科布雷，并涉及缅因州医学中心新成立的(1998)分子医学中心的四名新研究人员(非R01资助的)和两名现有研究人员的合作利益。由于该计划的PI在细胞和分子水平对内皮细胞生物学的长期研究兴趣，以及支持血管生成计划的机构承诺，本主题侧重于血管生成中的信号范式。申请这一奖项的动机包括：(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，在该领域建立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)提供在机械血管生物学广泛领域建立国际公认的非营利性研究机构所需的资源。该应用包括在血管生成领域选定的五个项目，感兴趣的领域包括：(I)成纤维细胞生长因子和Jagge1信号在调节缺血性心脏损伤后的弦形成和稳定的侧支循环系统中的协同作用，(Ii)FGFR信号的拮抗和Sprouty对分支的调节，(Iii)体内炎症介导的FGF2作为与纤溶酶原片段的共价复合体的释放，(Iv)转化生长因子β受体相关蛋白endoglin，以介导动静脉畸形和(V)作为小管形成的转录调节剂的Twist。到2001年，计划的扩展将包括招募6名具有遗传、细胞和分子信号专业知识的研究人员，这些专家由(I)蛋白酶及其抑制剂、(Ii)细胞外基质、(Iii)钙粘素、(Iv)淋巴生成和血管生成中的血管内皮生长因子、(V)G蛋白偶联受体和(Vi)细胞内交易调节，但该奖项的资源将仅用于(I)和(Ii)领域的计划扩展。预计这一奖项不仅将使技术转让成为可能。对莫尔来说。地中海医院。以更快、更有效的速度实现其目标，但这些研究人员得出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。

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.