Alcohol & FAS-Mediated Apoptosis in Polarized Liver Cell

贝尼塔·L·麦克维克于1997年在内布拉斯加大学医学中心(UNMC)获得博士学位， 曾在退伍军人管理局肝脏研究部的迪恩·图马博士和卡罗尔·凯西博士的实验室工作 从那时起，他就在内布拉斯加州的奥马哈中心工作。肝脏研究小组在确定这一点方面发挥了重要作用 长期饮用酒精会导致各种病理后果，但进一步澄清 乙醇引起肝毒性的机制(S)是必需的。最近，麦克维克博士和 同事们已经确定使用成纤维细胞/肝癌杂交细胞系(WIF-B)作为研究的模型 乙醇对细胞过程的影响。这种生理上重要的极化的产生 模型(这不能用常规的分离肝细胞来完成)将使蛋白质的评估成为可能 酒精存在下的贩运事件(Fas/CD95死亡受体)与 肝细胞极性与细胞凋亡。具体地说，麦克维克博士在这项拨款中提出的研究目标 包括1)进一步表征乙醇对Fas运输的影响和2)确定特定的 参与乙醇诱导Fas移位的调节因子及其与 Fas诱导细胞凋亡的机制。死亡受体转运和信号转导的研究及应用 WIF-B模型是麦克维克博士感兴趣的新领域。对于这些研究，她建议使用 需要额外培训的几种技术(即免疫组织化学和微量注射分析) 和专门化教学。McVicker博士可以访问UNMC的共焦和流式细胞仪核心实验室 并支持在这些方法中进行培训协商。此外，她还支持学习具体的 在天主教大学Pamela Tuma博士(WIF-B细胞使用方面的专家)的指导下进行的技术 总体而言，这项拟议工作的完成将为 未来乙醇治疗后肝功能和存活率的独立研究进展的经验。

Benita L. McVicker received her PhD from The University of Nebraska Medical Center (UNMC) in 1997 and has worked in the laboratories of Drs. Dean Tuma and Carol Casey in the Liver Study Unit at the VA Medical Center in Omaha, Nebraska since that time. The Liver Study Unit has been instrumental in establishing that chronic ethanol consumption can lead to a variety of pathological consequences, yet further clarification of the mechanism(s) by which ethanol causes hepatotoxic conditions is required. Recently, Dr. McVicker and co-workers have identified the use of a fibroblast/hepatoma hybrid cell line (WIF-B) as a model for studying the effects of ethanol on cellular processes. The generation of such a physiologically important polarized model (that cannot be accomplished with regular isolated hepatocytes) will enable the evaluation of protein trafficking events (Fas/CD95 death receptor) in the presence of alcohol in relation to alterations in hepatocyte polarity and apoptosis. Specifically, the goals of Dr. McVicker's research presented in this grant include 1) further characterization of ethanol's effects on Fas trafficking and 2) to identify the role of specific regulators that are involved in ethanol-induced Fas translocation and the correlation of these effects with Fas-induced apoptosis mechanisms. The study of death receptor trafficking and signaling as well as the use of the WIF-B model are new areas of interest to Dr. McVicker. For these studies, she has proposed to use several techniques (i.e.immunohistochemistry and microinjection assays) that will require additional training and specialized instruction. Dr. McVicker has access to the confocal and flow cytometry core labs at UNMC and has support for training consultations in those methods. In addition, she has support to leam specific techniques under the direction of Dr. Pamela Tuma (an expert in the use of WIF-B cells) at The Catholic University in Washington D.C. Overall, the completion of this proposed work will provide the mentored experience to progress to future independent study of liver function and survival following ethanol treatment.