MECHANISM OF NON-CLASSICAL RELEASE OF THE ANGIOGENESIS REGULATOR, IL1-ALPHA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。普鲁多夫斯基的这个项目代表了他对缺乏信号肽的蛋白质的非经典释放机制的长期生产性兴趣的一个新方向。这些研究是通过与T.Maciag的合作而发展起来的，尽管假设和方法是由Prudovsky博士独立开发的。本项目旨在研究促炎症细胞因子IL1-α的释放机制，以及该机制与促血管生成因子FGF1的不同之处。这些研究将对设计新的IL1-α和FGF1释放抑制剂具有翻译潜力和治疗意义。预计该项目将在检查GIST肿瘤或周围炎性细胞释放IL1-α方面与项目2(L.Liww)互动。此外，预计该项目将与我们的两名高级应聘人员(项目7和8)互动，他们的研究领域将涉及血管壁中的炎症机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The project by I. Prudovsky represents a new direction for his long-term productive interest in non-classical release mechanisms for proteins lacking signal-peptides. These studies have evolved through collaboration with T. Maciag, although the hypothesis and approach were developed independently by Dr. Prudovsky. This project proposes to examine the mechanism of release of the pro-inflammatory cytokine IL1-alpha, and how this mechanism differs from that of the pro-angiogenic factor FGF1. These studies will have translational potential and therapeutic implications for the design of novel inhibitors of IL1-alpha and FGF1 release. It is anticipated that this project will be interactive with Project 2 (L. Liaw) in examining the release of IL1-alpha from GIST tumors or surrounding inflammatory cells. Furthermore it is anticipated that this project will be interactive with both of our senior recruits (Projects 7 and 8), whose area of research interest will involve inflammatory mechanisms in the vessel wall.