The Role of Lymphotoxin Receptor in Liver Regeneration

淋巴毒素受体在肝脏再生中的作用

• 批准号: 6868111
• 负责人: ROBERT A. ANDERS
• 金额: $ 13.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868111
• 关键词: apoptosis; cytokine receptors; genetically modified animals; hepatectomy; laboratory mouse; ligands; liver cells; liver regeneration; lymphocyte; necrosis; polymerase chain reaction; terminal nick end labeling; tumor necrosis factor beta

DESCRIPTION (provided by applicant): Candidate: I plan to pursue a career performing fundamental research in an academically strong Pathology Department. My long term goal is to understand the basic mechanisms of diseases affecting the liver and to apply that knowledge to combat human chronic liver diseases. My current plan is to uncover which LT beta receptor ligands are essential for liver regeneration and which lymphocyte subsets are involved in delivering the LT beta receptor ligands to the liver parenchyma. I am very eager and committed to continuing this project. The Mentored Clinical Scientist Development Award is critical to continue my progress towards becoming an independent physician scientist. This award will allow me to develop and expand my project as well as gain more specific and mentored training in the field of immunology. Environment: I am interested in liver pathology and the University of Chicago has an active liver transplantation program which provides a wealth of experience in interpreting liver biopsies. Dr. Yang-Xin Fu, the mentor, has extensive experience in cytokine research, the lymphotoxin system and training scientists to become independent basic research investigators. Research project: The tumor necrosis alpha (TNF-alpha) superfamily is a large group of ligands and receptors with diverse biologic activities. TNF-alpha signaling through the TNF receptor 1 is a proximal event in liver regeneration. However, the contribution of TNF-alpha related family member to liver regeneration has not been explored. The contribution of the lymphotoxin ligand and receptors system to liver regeneration is largely unknown. Our preliminary data suggests that signaling through lymphotoxin is involved in liver regeneration. We propose that delivery of lymphocyte derived lymphotoxin to the liver following partial hepatectomy is necessary for recovery of hepatic mass.

描述（由申请人提供）： 候选人：我计划在学术实力雄厚的病理学系从事基础研究。我的长期目标是了解影响肝脏的疾病的基本机制，并将这些知识应用于对抗人类慢性肝病。我目前的计划是揭示哪些LT β受体配体对肝再生至关重要，哪些淋巴细胞亚群参与将LT β受体配体传递到肝实质。我非常渴望并致力于继续这个项目。指导临床科学家发展奖对于我继续成为一名独立医生科学家至关重要。这个奖项将使我能够发展和扩大我的项目，并获得免疫学领域更具体和更有指导的培训。 工作环境：我对肝脏病理学很感兴趣，芝加哥大学有一个活跃的肝移植项目，在解释肝活检方面提供了丰富的经验。导师傅洋欣博士在细胞因子研究、光合作用系统和培养科学家成为独立的基础研究调查者方面拥有丰富的经验。 研究项目：肿瘤坏死因子-α（TNF-α）超家族是一个具有不同生物活性的配体和受体的大组。通过TNF受体1的TNF-α信号传导是肝再生中的近端事件。然而，TNF-α相关家族成员对肝再生的贡献尚未被探索。淋巴毒素配体和受体系统对肝脏再生的贡献在很大程度上尚不清楚。我们的初步数据表明，通过光氧还蛋白的信号传导参与了肝再生。我们认为，部分肝切除术后，淋巴细胞源性光毒素向肝脏的输送对于肝脏肿块的恢复是必要的。