REACTIVE OXYGEN SPECIES AS MEDIATORS OF TGF-B1 ACTIONS

描述 (改编自申请人的摘要)这是一份 为Victor J.Thanickal博士提供的额外研究培训 完成一个项目，这将使他具有竞争力 独立支持。他现在已经花了两年的时间进行研究培训 团契，在此期间他发现了一种新的NADH的存在 某些细胞表面的氧化酶，包括成纤维细胞的 在肺纤维化的发展中起重要作用。此外，他还 发现这种酶是由转化生长因子-β1刺激的，转化生长因子-β1的存在 与纤维化有关，并有能力增强 巨噬细胞趋化因子的产生及其自分泌 转化生长因子-β1本身，这可能使这一过程永久化。他的理论是 转化生长因子-β1刺激H202产生可能是一种信号转导事件 纤维化过程，希望通过设计的研究进一步评估这一过程 以：1)评估NADH氧化酶的酶性质；2)评估 蛋白质酪氨酸研究中可能的相关信号转导途径 磷酸化；以及3)确定与可能转录的关联 激活M-CSF和转化生长因子-β1基因的途径。巴里·范伯格博士将 继续赞助和监督他的工作。除了日报之外 由B.Fanburg博士和Thanickal博士指导的研究将回顾他的 每季度进展一次，委员会成员包括诺曼·克林斯基博士、欧文 塔夫茨大学医学院的Arias和Brent Cochran和Will 在邻近的萨克勒研究生院学习相关课程 塔夫茨大学医学院。

DESCRIPTION (Adapted from the applicant's abstract) This is an application for additional research training for Dr. Victor J. Thannickal while he pursues accomplishment of a project that will allow him to be competitive for independent support. He has now spent two years in a research training fellowship, during which time he has identified the presence of a novel NADH oxidase on certain cell surfaces including that of the fibroblast which is important in the development of pulmonary fibrosis. Furthermore, he has found that this enzyme is stimulated by TGF-Bl, a cytokine whose presence has been associated with fibrosis and which is capable of enhancing the production of a macrophage chemoattractant and the autocrine production of TGF-B1 itself which may perpetuate the process. He theorizes that stimulation of H202 production by TGF-B1 may be a signaling event in the fibrotic process and wishes to evaluate this further with studies designed to: 1) assess enzymatic properties of the NADH oxidase; 2) evaluate possible related transduction pathways through studies of protein tyrosine phosphorylation; and 3) determine association with possible transcription pathways that activate M-CSF and TGF-B1 genes. Dr. Barry Fanburg will continue to sponsor and supervise his work. In addition to the daily mentored research by Dr. B. Fanburg and Dr. Thannickal will review his progress quarterly with a committee that includes Drs. Norman Krinsky, Irwin Arias and Brent Cochran of the Tufts University School of Medicine and will take relevant course work at the adjacent Sackler Graduate School of the Tufts University School of Medicine.