CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN ANGIOGENESIS

血管生成是从现有结构形成新血管，并且涉及伤口修复的调节和许多疾病状态（包括实体瘤生长）的病理生物学。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，这些信号由生长因子、细胞因子、蛋白酶、脂质和细胞外基质的组分的活性修饰，因此对于专注于血管生成的机构来说，包括这些和其他领域的实验计划（例如机制和细胞内运输）是重要的。因此，本申请请求IDEA计划的支持，以建立血管生成中的COBRE，并涉及缅因州医学中心新成立（1998年）的分子医学中心的四名新（非R01资助）和两名已建立研究者的合作利益。该主题的重点是血管生成的信号转导范式，这是由于该计划的PI在细胞和分子水平上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。这一申请的动机包括利用这一奖项（一）支持这一领域有前途的年轻独立调查员，（二）扩大现有的机构资源，以创造一个更大的临界质量的机制为导向的初级和高级调查员在这一领域，（四）提供必要的资源，以建立一个国际公认的非在机械血管生物学的广泛领域的盈利研究机构。该申请由在血管生成领域中选择的五个项目组成，并且感兴趣的领域包括以下机制：（i）FGF和Jagged 1信号传导之间在缺血性心脏损伤后的弦形成的调节和稳定的侧支循环系统的调节中的协同性，（ii）FGFR信号传导的拮抗作用和Sprouty对分支的调节，（iii）体内炎症介导的FGF 2作为与纤溶酶原片段的共价复合物的释放，（iv）TGF β受体相关蛋白，内皮糖蛋白，介导动静脉畸形和（v）Twist作为小管形成的转录介导物。到2001年，该计划将扩大，包括招募6名研究人员，他们具有遗传、细胞和分子信号传导方面的专门知识，这些信号传导由（i）蛋白酶及其抑制剂，（ii）细胞外基质，（iii）钙粘蛋白，（iv）淋巴细胞生成和血管生成中的VEGF，（v）G蛋白偶联受体和（vi）细胞内运输，但该奖项的资源将仅用于计划在以下领域的扩展（（i）及（ii）。预计这一奖项不仅将使中心。对于摩尔但是这些研究者的发现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.