DTMI-Center for Thrombotic and Hemostatic Disorders

DTMI-血栓和止血疾病中心

• 批准号: 8656777
• 负责人: Richard Clinton Becker
• 金额: $ 226.91万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656777
• 关键词: Acute; Address; Animals; Antidotes; Antiplatelet Drugs; Basic Science; Blood Platelets; Blood Vessels; Caring; Cells; Clinical; Clinical Research; Coagulation Process; Complication; Disease; Environment; Fibrinolytic Agents; Hemorrhage; Hemostatic Agents; Home environment; Human; Individual; Institutes; Laboratories; Methods; Modeling; Molecular; Monitor; Names; Oligonucleotides; Operative Surgical Procedures; Patients; Phase; Phase I Clinical Trials; Platelet aggregation; Procedures; RNA; Research; Research Personnel; Research Project Grants; Safety; Sampling; Seasons; Therapeutic; Thrombosis; Translating; Translational Research; Translations; Trauma; Universities; aptamer; base; clinically relevant; novel strategies; prevent; programs; translational medicine; von Willebrand Factor

The overall objective of the Duke Translational Medicine Institute Center for Thrombotic and Hemostatic Disorders (DTMI-CTHD) is to establish a home for and provide support for investigators focused upon developing novel approaches to treat thrombotic and hemostatic diseases at Duke University. As its name indicates, the DTMI-CTHD will be tightly integrated with the CTSA supported Duke Translational Medicine Institute, which is the home for all translational and clinical research at Duke. The scientific focus of the DTMI-CTHD is on treating thrombotic disease in acute care prothrombotic settings. Profound antithrombotic therapy is critical during both percutaneous and surgical revascularization procedures to prevent deleterious effects of coagulation and platelet aggregation triggered by foreign materials and vascular trauma. Such potent antithrombotic therapy is associated with the common complication of bleeding which makes management of such therapy challenging. To address this challenge, we have established a translational research program that has three research projects and three cores. Each project and core is led by a seasoned investigator(s). Project 1 will evaluate potent, yet antidote controllable combinations of antithrombotic agents in cell and animal based models. Project 2 will translate the first antidote controllable antiplatelet agent, a RNA aptamer against von Willebrand factor (VWF) and its matched antidote oligonucleotide, into phase 1a and 1b studies. Project 3 will employ clinical samples to develop unique laboratory profiles that can be applied to various clinical settings to predict the safety and efficacy of targeted antithrombotic therapy. Collectively these projects will result in 1.) a more thorough basic mechanistic understanding of the prothrombotic environment engendered during common revascularization procedures, 2.) translation of a novel approach to control platelet activity into a phase 1 clinical trial to begin to address a major challenge of antithrombotic therapy, bleeding and 3.) methods to identify and manage the optimal antithrombotic therapy for treatment of individual patients. The molecular, educational and administrative cores will support each of these projects as well as facilitate basic, translational and clinical research on thrombotic and hemostatic disorders across the Duke campus. Each project and core will be briefly discussed below along with the overall research environment at Duke.

杜克转化医学研究所血栓和止血疾病中心（DTMI-CTHD）的总体目标是为杜克大学专注于开发治疗血栓和止血疾病的新方法的研究人员建立一个家园并提供支持。正如其名称所示，DTMI-CTHD将与CTSA支持的杜克转化医学研究所紧密结合，该研究所是杜克所有转化和临床研究的所在地。DTMI-CTHD的科学重点是在急性血栓前护理环境中治疗血栓性疾病。在经皮和外科血运重建手术中，深入的抗血栓治疗至关重要，以防止异物和血管创伤引发的凝血和血小板聚集的有害影响。这种有效的抗血栓治疗与常见的出血并发症有关，这使得这种治疗的管理具有挑战性。为了应对这一挑战，我们已经建立了一个转化研究计划，有三个研究项目和三个核心。每个项目和核心都由一位经验丰富的研究人员领导。项目1将在基于细胞和动物的模型中评价有效的，但解毒剂可控的抗血栓药物组合。项目2将把第一种解毒剂可控抗血小板药物，一种针对血管性血友病因子（VWF）的RNA适体及其匹配的解毒剂寡核苷酸转化为1a期和1b期研究。项目3将使用临床样本开发独特的实验室特征，可应用于各种临床环境，以预测靶向抗血栓治疗的安全性和有效性。这些项目将共同导致1。对常见血运重建过程中产生的促血栓形成环境的更彻底的基本机制理解，2.）将控制血小板活性的新方法转化为1期临床试验，以开始解决抗血栓治疗、出血和3.）确定和管理用于治疗个体患者的最佳抗血栓形成疗法的方法。分子，教育和行政核心将支持这些项目中的每一个，以及促进整个杜克校园的血栓和止血疾病的基础，转化和临床研究。每个项目和核心将简要讨论下面沿着在杜克的整体研究环境。