CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN ANGIOGENESIS

血管生成是指从现有结构中形成新血管，并参与伤口修复的调节和包括实体瘤生长在内的许多疾病状态的病理生物学。由于血管生成是由生长因子、细胞因子、蛋白酶、脂质和细胞外基质成分的活性修饰的受体介导信号的复杂相互作用调节的，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项目，如机制和细胞内运输，是很重要的。因此，本申请请求IDeA计划的支持，以建立血管生成COBRE，并涉及缅因州医学中心新成立的（1998年）分子医学中心的四名新成员（非r01资助）和两名已成立的研究人员的合作利益。该主题侧重于血管生成中的信号范式，这是该项目的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和机构承诺支持血管生成项目的结果。此次申请的动机包括利用该奖项(1)支持该领域有前途的年轻独立研究者，(2)扩大现有机构资源，以在该领域培养更多以机械为导向的初级和高级研究人员，满足研究者的需求，(4)为在机械血管生物学的广泛领域建立一个国际公认的非营利性研究机构提供必要的资源。该应用程序由血管生成领域选择的五个项目组成，感兴趣的领域包括(i) FGF和Jagged 1信号在调节弦形成和调节缺血性心脏损伤后稳定的侧支循环系统中的协同作用机制；（ii） FGFR信号的拮抗作用和斯普罗蒂对分支的调节。（iii）炎症介导的FGF2在体内作为纤溶酶原片段的共价复合物释放，（iv） tgf β受体相关蛋白内啡肽介导动静脉畸形，(v) Twist作为小管形成的转录介质。到2001年，项目扩展将包括招募6名具有遗传、细胞和分子信号专业知识的研究人员，这些专业知识包括：(1)蛋白酶及其抑制剂，(2)细胞外基质，(3)钙粘蛋白，(4)淋巴生成和血管生成中的VEGF， (5) g蛋白偶联受体和(6)细胞内运输，但该奖项的资源将仅用于项目扩展领域(1)和(2)。预计该奖项不仅将使中央研究中心。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。

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.