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: 7253291
• 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/7253291
• 关键词: Abbreviations; Acute; Address; Adoptive Transfer; Affect; Apoptosis; Award; Basic Science; Binding; Biology; Bromodeoxyuridine; Cause of Death; Cell division; Cells; Chicago; Chimeric Proteins; Chronic; Chronic Disease; Commit; DNA; DNA biosynthesis; DNA chemical synthesis; Data; Development; Disease; Environment; Equilibrium; Event; Family; Family member; Follicular Dendritic Cells; Genes; Goals; Health; Hepatic Mass; Hepatocyte; Herpesviridae; Human; Immune system; Immunology; Inflammatory; Injury; Knockout Mice; Knowledge; Ligands; Liver; Liver Failure; Liver Regeneration; Liver diseases; Liver parenchyma; Lymphocyte; Lymphocyte Subset; Mediator of activation protein; Medical; Membrane; Mentored Clinical Scientist Development Award (K08); Mentors; Molecular; Mus; NF-kappa B; Natural regeneration; Necrosis; Partial Hepatectomy; Pathology; Pattern; Phenotype; Physicians; Principal Investigator; Production; Range; Receptor Signaling; Recovery; Research; Research Personnel; Research Project Grants; Role; Scientist; Signal Transduction; Stimulus; Structure of aggregated lymphoid follicle of small intestine; System; T-Lymphocyte; TNF gene; Testing; Therapeutic; Time; Training; Tumor Necrosis Factor Receptor; Tumor Necrosis Factor-Beta; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States; Universities; Yang; base; career; cytokine; expectation; experience; fundamental research; high voltage electron microscopy; human TNF protein; in vivo Model; innovation; interest; intrahepatic; liver biopsy; liver transplantation; lymphotoxin beta receptor; novel; novel therapeutics; programs; receptor; recombinase; reconstitution; research study; response; therapeutic target; tumor

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)： 应聘者：我打算在一个学术实力很强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与人类慢性肝病作斗争。我目前的计划是揭示哪些LTβ受体配体对肝脏再生是必不可少的，以及哪些淋巴细胞亚群参与将LTβ受体配体输送到肝实质。我非常渴望并致力于继续这个项目。导师临床科学家发展奖对于我继续成为一名独立的内科科学家至关重要。这一奖项将使我能够发展和扩大我的项目，并在免疫学领域获得更具体和更有指导的培训。 环境：我对肝脏病理学感兴趣，芝加哥大学有一个活跃的肝脏移植项目，在解释肝脏活检方面提供了丰富的经验。导师傅阳新博士在细胞因子研究、淋巴毒素系统以及培养科学家成为独立的基础研究研究者方面拥有丰富的经验。 研究项目：肿瘤坏死因子超家族是一大类具有多种生物学活性的配体和受体。通过肿瘤坏死因子受体1传递的肿瘤坏死因子-α信号是肝再生过程中的一个近端事件。然而，肿瘤坏死因子-α相关家族成员在肝再生中的作用尚不清楚。淋巴毒素配体和受体系统对肝脏再生的作用在很大程度上是未知的。我们的初步数据表明，通过淋巴毒素发出的信号参与了肝脏再生。我们认为，肝部分切除后向肝脏输送淋巴源性淋巴毒素对于肝脏质量的恢复是必要的。