Translational Control of Megakaryocyte and Platelet Gene Expression in Disease

总体摘要/摘要 这一杰出调查者奖R35计划解决了以前未探索的机制，通过 基因在翻译水平上的表达调控控制着巨核细胞和血小板的功能， 在健康和疾病的背景下。研究将在人类和小鼠身上进行基础和临床研究，以 全面确定汇聚在真核起始因子4E上的翻译途径 (EIF4E)调节巨核细胞和血小板生物学。翻译控制通路在 巨核细胞以前没有被研究过，它们在循环血小板中的功能意义是 不确定，也不清楚疾病情况如何改变巨核细胞的翻译反应和 血小板。因此，研究目标的成功完成将填补知识的主要空白，这些知识需要 在心脏、肺和血液研究方面。生成的结果还将决定翻译控制是否 目前正在临床上测试的途径抑制剂对巨核细胞和 血小板。

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.