HEMATOPOIETIC MAST CELL REGULATORY FACTORS

肥大细胞效应物的异常产生与许多 重要疾病，包括哮喘、炎症性肠病和 动脉粥样硬化，仅举几例。 肥大细胞调节功能障碍 肥大细胞增多症引起的症状最能说明这一点。 中 相关现象，在动物中观察到类似症状， 重组干细胞因子的临床试验 虽然许多 报告描述肥大细胞，大部分肥大细胞的发育仍然是一个问题。 谜 本项目研究的长期目标是 鉴定在调节肥大细胞中起作用新因子 发展 我们的主要兴趣是抑制或 以较低优先级抑制肥大细胞分化或成熟 刺激因素。 抑制因素会有很大的价值， 例如在减少上述使用因子治疗的副作用方面 例如干细胞因子。 有大量证据表明， 监管因素，并在这方面的目标，这一阶段 项目是开发和表征以下分子工具：1） 从肥大细胞中消减特异性结构域富集文库 2）来自产生调节子的细胞的表达文库; 3)来自产生调节剂的细胞的噬菌体展示文库。 这些 文库将在高通量测定中测试它们对 肥大细胞发育 鉴于这项研究的成功， 这些基因将在该项目的第二阶段进行研究。

Aberrant production of mast cell effectors is implicated in many important diseases including asthma, inflammatory bowel disease and atherosclerosis, to name just a few. Dysfunction of mast cell regulation is best illustrated by the symptoms resulting from mastocytosis. In a related phenomenon, similar symptoms have been observed in animal and clinical trials with the recombinant Stem Cell Factor. While many reports describe mast cells, much of mast cell development remains a mystery. The long term goal of the research in this project is to identify novel factors which function in regulating mast cell development. Our primary interest is in factors which inhibit or suppress mast cell differentiation or maturation, with a lower priority on stimulatory factors. Inhibitory factors would have significant value, for example in reducing the side effects above of therapy with factors such as stem cell factor. There is considerable evidence for novel regulatory factors, and in this light the objective of this phase I project is to develop and characterize the following molecular tools: 1) subtracted specific domain enrichment libraries from mast cell progenitors; 2) expression libraries from cells which produce regulators; 3) phage display libraries from cells which produce regulators. These libraries will be tested in high throughput assays for their effects on mast cell development. Given success in this research, the cloning of these genes will be pursued in phase II of this project.