GROWTH CONTROL OF NORMAL AND CIRRHOTIC HEPATOCYTES

首席研究员的长期目标是成为 独立资助的学术外科科学家在该领域的 胃肠手术 临床研究者研究项目 在外科培训期间提供了丰富的初步经验， 大型动物生理学研究。 这项建议旨在培训 首席研究员作为一个学术外科分子生物学家。 这项建议包括教学工作，辅导细胞培养， 在Reid博士指导下进行分离和流式细胞术，并具有信号处理经验 转导，差异显示PCR和基因表达在Dr. 布伦纳完成这项计划将允许校长 研究者成为临床科学家，重点是 胃肠外科和分子生物学。 北卡罗来纳大学教堂山分校有着丰富的基础科学研究传统， 胃肠道生物学和疾病中心等项目， 分子生物学与生物技术专业这些程序 提供分子生物学、免疫测定、生物统计学方面的专业知识， 教学课程工作。 普通实验室的实验室空间和使用 设备将由里德博士和布伦纳博士提供 该建议的重点是生长控制机制的主要和 肝细胞对转录抑制的应答 因子核因子κ β（NF κ B）。 体内实验 证明NF κ B是防止肝细胞凋亡所必需的 或肝再生过程中肝细胞中G2/M细胞周期阻滞。 这项提议旨在确定细胞凋亡或细胞周期停滞是否是细胞凋亡的关键因素。 生长控制的主要机制。 此外，差异化显示 PCR将用于鉴定与生长控制有关的新基因 在正常肝细胞和肝硬化肝细胞中。鉴定 新的或差异调节的肝细胞生长控制基因可 提供关于改变生长控制的信息， 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.