Expression of Alternatively Spliced Human Tissue Factor

选择性剪接的人组织因子的表达

• 批准号: 6868044
• 负责人: VLADIMIR BOGDANOV
• 金额: $ 11.04万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-07 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868044
• 关键词: RNA interference; RNA splicing; cell line; gene induction /repression; genetic regulatory element; human genetic material tag; lipopolysaccharides; nucleic acid structure; thromboplastin

DESCRIPTION (provided by applicant): I, Vladimir Bogdanov, am applying for this research development award in order to finalize my transition into an independent research scientist. The immediate goals are: 1) to acquire new laboratory skills and generate novel research data that would enable me to compete for regular research project grant support (RO1), 2) to acquire first-hand experience in being a principal investigator, and 3) to make substantial progress in elucidating the mechanisms involved in regulation of human tissue factor (TF) pre-mRNA processing in monocytic cells. Specifically, I propose to study regulatory mechanisms responsible for generation of alternatively spliced human tissue factor (asHTF) in monocytes. asHTF, a recently identified molecule, is a soluble, biologically active form of human tissue factor generated by alternative splicing. It is present in circulating blood and thrombi and interacts with platelets under shear conditions. Full-length membrane-bound TF and asHTF are both present in arterial and ex-vivo thrombi. Initial results show that circulating monocytes serve as one of the major sources of asHTF protein in human plasma. Thus, mechanics of tissue factor pre-mRNA splicing in monocytic cells is the primary research objective of the proposed study. In addition, I propose to achieve selective down-regulation of full-length membrane bound TF and asHTF mRNA in monocytic cells by a novel technique of RNA interference and assess the impact of this down-regulation on the total coagulant potential of monocytic cells.

描述（由申请人提供）：