Regulation of non-canonical NF-kb signaling

非规范 NF-kb 信号传导的调节

• 批准号: 8085851
• 负责人: Bahram Razani
• 金额: $ 3.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8085851
• 关键词: Address; Area; Autoimmune Diseases; Autoimmune Process; Biochemical; Blood; Cells; Clinical; Clinical Medicine; Defect; Development; Disease; Doctor of Philosophy; Educational Curriculum; Environment; Feedback; Foundations; Goals; Hematological Disease; Immune; Investigation; Knowledge; Ligation; Lupus; Lymphoma; Medical; Modification; Molecular; Multiple Myeloma; NF-kappa B; NFKB Signaling Pathway; Pathology; Pathway interactions; Patients; Pharmacologic Substance; Phosphorylation; Phosphotransferases; Physicians; Play; Protein-Serine-Threonine Kinases; Proteins; Regulation; Rheumatoid Arthritis; Role; Scientist; Signal Pathway; Signal Transduction; Site; Source; Students; Training; Translating; base; career; improved; kinase inhibitor; medical schools; novel; receptor; research study; skills; translational medicine

DESCRIPTION (provided by applicant): This proposal aims to provide an environment for the scientific and medical training of a young physician- scientist. As part of the training the student will complete both MD and PhD degrees, with a specific scientific emphasis during his PhD on the development of autoimmune and proliferative immune cell disorders. Training as part of the PhD will be focused on investigating the basic biochemical and molecular regulation of the non-canonical NF-kB pathway. This signaling pathway appears to be hyperactive in autoimmune diseases such as lupus and rheumatoid arthritis as well as proliferative immune cell disorders such as multiple myeloma and lymphoma. Although dysregulation of this pathway seems to contribute to several important blood disorders, how the pathway is normally regulated is poorly understood. The student has identified a previously unappreciated interaction between components of this pathway which may play an important role in the pathway's regulation. This proposal aims to fully understand the biochemical basis and functional significance of this novel interaction. Enhanced knowledge of how non-canonical NF-kB signaling is regulated will allow for an improved understanding of the pathologies, such as lupus and multiple myeloma, in which this pathway plays a role. Indeed, defects in new aspects of non-canonical NF-kB regulation may ultimately be found to be the source of disease development in certain patients. Furthermore, nuanced understanding of how non-canonical signaling is regulated may allow for novel targets for pharmaceutical manipulation of the pathway in disease treatment. Although the experiments described here are highly biochemical they will provide an intellectual and technical foundation to be used in the student's later career in translational medicine. Indeed, as part of the final aim of the proposal, the student will be trained for the clinical aspect of his career as a physician scientist. This will be achieved through participation in the clinical years of the medical school curriculum. This proposal, then, aims to prepare a young student for a career as a physician scientist, and as part of the training addresses important scientific questions in the area of blood pathology.

描述（由申请人提供）：该提案旨在为年轻医师科学家的科学和医学培训提供环境。作为培训的一部分，学生将完成医学博士和博士学位，其博士期间的具体科学重点是自身免疫和增殖性免疫细胞疾病的发展。作为博士学位一部分的培训将侧重于研究非经典 NF-kB 通路的基本生化和分子调控。该信号通路在狼疮和类风湿性关节炎等自身免疫性疾病以及多发性骨髓瘤和淋巴瘤等增殖性免疫细胞疾病中似乎过度活跃。尽管该通路的失调似乎会导致几种重要的血液疾病，但对该通路的正常调节方式却知之甚少。学生已经发现了该途径各组成部分之间以前未被认识到的相互作用，该相互作用可能在该途径的调节中发挥重要作用。该提案旨在充分了解这种新型相互作用的生化基础和功能意义。增强对非典型 NF-kB 信号传导如何调节的了解将有助于更好地了解该通路发挥作用的病理学，例如狼疮和多发性骨髓瘤。事实上，非规范 NF-kB 调节新方面的缺陷最终可能被发现是某些患者疾病发展的根源。此外，对非规范信号传导如何调节的细致了解可能会为疾病治疗中该途径的药物操纵提供新的靶标。尽管这里描述的实验是高度生物化学的，但它们将为学生以后的转化医学职业生涯提供知识和技术基础。事实上，作为该提案最终目标的一部分，学生将接受其作为医师科学家职业生涯的临床方面的培训。这将通过参与医学院课程的临床课程来实现。因此，该提案旨在帮助年轻学生为医师科学家的职业生涯做好准备，并作为培训的一部分解决血液病理学领域的重要科学问题。