GROWTH CONTROL OF NORMAL AND CIRRHOTIC HEPATOCYTES

首席研究员的长期目标是成为一名 独立资助的外科领域的学术科学家 胃肠道手术。临床研究人员研究计划 在外科培训期间提供了强大的初步经验 大型动物生理学研究。这项提案旨在培训 作为学术外科分子生物学家的首席研究员。 这项建议包括教学工作，细胞培养的指导和 在里德博士和信号经验的指导下进行分离和流式细胞术 转导、差异显示和基因表达。 布伦纳。完成这一计划将允许校长 调查员将成为一名临床科学家，专注于 胃肠外科和分子生物学。 北卡罗来纳大学教堂山拥有丰富的基础科学研究和 胃肠道生物学和疾病中心等项目 分子生物学和生物技术专业。这些计划 提供分子生物学、免疫分析、生物统计学和 教育性的课程作业。普通实验室的空间和用途 设备将由里德博士和布伦纳博士提供。 这项建议侧重于初级和初级的生长控制机制。 肝硬变肝细胞对转录抑制的反应 核因子kappaB(NFkappaB)。活体实验 证明NFkappaB是防止肝细胞凋亡所必需的 或肝再生过程中肝细胞的G2/M期停滞。 这项提案旨在确定细胞凋亡或细胞周期停滞是否是 生长控制的主要机制。此外，差异显示 聚合酶链式反应将被用来识别与生长控制有关的新基因 在正常肝细胞和肝硬变肝细胞中。身份识别 新的或差异调节的肝细胞生长控制基因可能 提供有关肝硬变的生长控制改变的信息 肝细胞。

The long-term goal of the principal investigator is to become an independently funded academic surgical scientist in the field of gastrointestinal surgery. A clinical investigator research program during surgical training provided a strong preliminary experience in large animal physiology studies. This proposal is designed to train the principal investigator as an academic surgical molecular biologist. This proposal includes didactic work, tutelage in cell culture and isolation and flow cytometry under Dr. Reid and experience in signal transduction, differential display PCR and gene expression under Dr. Brenner. Completion of this program will allow the principal investigator to become a clinical scientist with a focus of gastrointestinal surgery and molecular biology. UNC-Chapel Hill has a rich tradition of basic science research and programs such as the Center for Gastrointestinal Biology and Disease and the Program in Molecular Biology and Biotechnology. These programs provide expertise in molecular biology, immunoassay, biostatistics and didactic course work. The laboratory space and use of common laboratory equipment will be provided by Drs. Reid and Brenner. This proposal focuses on the growth control mechanisms of primary and cirrhotic hepatocytes in response to inhibition of the transcription factor nuclear factor kappa beta (NFkappaB). In vivo experiments demonstrated that NFkappaB is necessary to prevent hepatocyte apoptosis or G2/M cell cycle arrest in hepatocytes during hepatic regeneration. This proposal aims to determine if apoptosis or cell cycle arrest is the primary mechanism of growth control. In addition, differential display PCR will be used to identify novel genes involved with growth control in both normal hepatocytes and cirrhotic hepatocytes. Identification of novel or differentially regulated hepatocyte growth control genes may provide information about altered growth control of cirrhotic hepatocytes.