Translational Control of Megakaryocyte and Platelet Gene Expression in Disease

疾病中巨核细胞和血小板基因表达的转化控制

• 批准号: 10569253
• 负责人: Andrew S Weyrich
• 金额: $ 73.09万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569253
• 关键词: Address; Award; Biology; Blood; Blood Platelets; Blood coagulation; Cells; Clinic; Disease; Eukaryotic Initiation Factor-4E; Gene Expression; Gene Expression Regulation; Health; Heart; Heart Diseases; Hematological Disease; Human; Knowledge; Lead; Lung; Lung diseases; Megakaryocytes; Mus; Myocardial Infarction; Pathway interactions; Patients; Research; Research Personnel; Role; Sepsis; Testing; clinical investigation; inhibitor; novel diagnostics; programs; response

Overall Summary/Abstract This Outstanding Investigator Award R35 program addresses previously-unexplored mechanisms by which regulation of gene expression at the translational level controls the functions of megakaryocytes and platelets, in the setting of health and disease. Studies will employ basic and clinical investigations in humans and mice to comprehensively determine how translational pathways that converge on Eukaryotic Initiation Factor 4E (eIF4E) regulate megakaryocyte and platelet biology. Roles for translational control pathways in megakaryocytes have not previously been studied, their functional significance in circulating platelets is uncertain, and it is unknown how disease situations alter translational responses of megakaryocytes and platelets. Thus, successful completion of the research objectives will fill key gaps in knowledge that need to be addressed in heart, lung, and blood research. Results generated will also determine if translational control pathway inhibitors, which are currently being tested in the clinic, have off-target effects on megakaryocytes and platelets.

摘要/Abstract 这个杰出的研究者奖R35计划解决了以前未探索的机制， 在翻译水平上对基因表达的调节控制巨核细胞和血小板的功能， in the setting设置of health健康and disease疾病.研究将采用人类和小鼠的基础和临床研究， 全面确定翻译途径如何汇聚在真核起始因子4 E （eIF 4 E）调节巨核细胞和血小板生物学。翻译控制途径在肿瘤细胞中的作用 巨核细胞以前没有研究过，它们在循环血小板中的功能意义是 不确定，也不知道疾病情况如何改变巨核细胞的翻译反应， 血小板因此，成功完成研究目标将填补知识的关键空白，需要 在心脏、肺和血液研究中得到了解决。生成的结果还将确定是否进行翻译控制 目前正在临床测试的途径抑制剂对巨核细胞具有脱靶效应， 血小板