GPIb-IX and VWF in thrombosis and thrombocytopenia
GPIb-IX 和 VWF 在血栓形成和血小板减少症中的作用
基本信息
- 批准号:10574144
- 负责人:
- 金额:$ 109.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-15 至 2030-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressBloodBlood PlateletsBlood coagulationComplexDevelopmentDiseaseFunctional disorderFundingFutureGlycoprotein IbGoalsGrantHemostatic functionInvestigationKnowledgeLigandsMediatingMolecularMolecular ConformationMouse StrainsMutationPathogenesisPathologyPhysiologicalPlasmaProcessReagentRegulationStructureSurfaceThrombocytopeniaThrombosisflexibilitymultidisciplinarynovel therapeuticsplatelet functionreceptortherapeutic developmentthromboinflammationthromboticvon Willebrand Factor
项目摘要
PROJECT SUMMARY
Understanding the interplay between blood, vessel, and shear flow is key to elucidate the pathophysiology
of thrombosis and related diseases. Both glycoprotein (GP)Ib-IX-V complex, an abundant receptor
complex on the platelet surface, and its ligand von Willebrand factor (VWF) in the plasma critically mediate
hemostasis, thrombosis, and thrombo-inflammation by sensing and responding to blood shear flow.
Although much is known about this important receptor-ligand pair, significant knowledge gaps, especially
the molecular mechanisms underlying their activation and regulation, have remained open. As the
continuation of two current R01 grants entitled “Structure and function of platelet glycoprotein Ib-IX-V
complex” and “Conformational activation of von Willebrand factor”, this proposed R35 project seeks to fill
several long-standing knowledge gaps and address controversial questions in our understanding of GPIb-
IX-V, VWF and related disease pathology. Through systematic, multidisciplinary analysis of inter-domain
interactions in GPIb-IX and VWF, we have recently identified the mechanosensory domain (MSD) in GPIb-
IX and the discontinuous autoinhibitory module (AIM) in VWF, leading to elucidation of their respective
activation mechanisms. In addition to significant implications on pathophysiology of many related
thrombotic and thrombocytopenic disorders, these mechanisms provide a coherent conceptual framework
for future mechanistic investigations and novel therapeutic development. In this project, we seek to
determine the structure of the GPIb-IX complex and VWF domains, resolve the current controversy about
the activation mechanism of VWF particularly the AIM conformation, and elucidate mechanisms that
regulate activities of GPIb-IX and VWF. To accomplish these goals, we will continue to develop new
reagents targeting a key domain, new constructs enabling interdisciplinary analysis, and new mouse
strains bearing key mutations to specifically modulate their activity. The seven-year funding period will
provide additional flexibility and continuity for pursuing difficult-to-get structures and developing key
reagents. Overall, completion of the proposed study will elucidate the fundamental activation and
regulation mechanisms of GPIb-IX-V and VWF, significantly advance our understanding of pathogenesis
of many thrombotic and thrombocytopenic diseases, and potentially identify new strategies to develop
treatments for these diseases.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Renhao Li其他文献
Renhao Li的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Renhao Li', 18)}}的其他基金
Conformational activation of von Willebrand factor
血管性血友病因子的构象激活
- 批准号:
9754253 - 财政年份:2018
- 资助金额:
$ 109.55万 - 项目类别:
Conformational activation of von Willebrand factor
血管性血友病因子的构象激活
- 批准号:
10183306 - 财政年份:2018
- 资助金额:
$ 109.55万 - 项目类别:
Conformational activation of von Willebrand factor
血管性血友病因子的构象激活
- 批准号:
9982098 - 财政年份:2018
- 资助金额:
$ 109.55万 - 项目类别:
GPIbalpha shedding and platelet clearance
GPIbalpha 脱落和血小板清除
- 批准号:
9109676 - 财政年份:2015
- 资助金额:
$ 109.55万 - 项目类别:
Specific Inhibition of Ectodomain Shedding of GPIb-alpha
特异性抑制 GPIb-α 的胞外域脱落
- 批准号:
8212483 - 财政年份:2011
- 资助金额:
$ 109.55万 - 项目类别:
Specific Inhibition of Ectodomain Shedding of GPIb-alpha
特异性抑制 GPIb-α 的胞外域脱落
- 批准号:
8047809 - 财政年份:2011
- 资助金额:
$ 109.55万 - 项目类别:
相似海外基金
Blood platelets: a key regulator of immune cross-talk of embryo with uterus toward cow pregnancy
血小板:胚胎与子宫对奶牛妊娠免疫串扰的关键调节因子
- 批准号:
22KF0017 - 财政年份:2023
- 资助金额:
$ 109.55万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Instrumenting blood platelets: nanosensors for cumulative shear and compression measurement
血小板仪器:用于累积剪切和压缩测量的纳米传感器
- 批准号:
10056867 - 财政年份:2020
- 资助金额:
$ 109.55万 - 项目类别:
Instrumenting blood platelets: nanosensors for cumulative shear and compression measurement
血小板仪器:用于累积剪切和压缩测量的纳米传感器
- 批准号:
10224326 - 财政年份:2020
- 资助金额:
$ 109.55万 - 项目类别:
The role of blood platelets in the regulation of inflammation
血小板在炎症调节中的作用
- 批准号:
278886 - 财政年份:2013
- 资助金额:
$ 109.55万 - 项目类别:
Spreading dynamics and force generation in blood platelets (A12)
血小板中的扩散动力学和力的产生 (A12)
- 批准号:
190886903 - 财政年份:2011
- 资助金额:
$ 109.55万 - 项目类别:
Collaborative Research Centres
Carbohydrate distribution in endothelial cells from various organs in relation to the reactivity with blood platelets
与血小板反应性相关的各种器官内皮细胞中的碳水化合物分布
- 批准号:
11670019 - 财政年份:1999
- 资助金额:
$ 109.55万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A NOVEL RGD-BINDING MEMBRANE PROTEIN ON BLOOD PLATELETS
血小板上新型 RGD 结合膜蛋白
- 批准号:
2220156 - 财政年份:1989
- 资助金额:
$ 109.55万 - 项目类别:
NOVEL RGD-BINDING MEMBRANE PROTEIN ON BLOOD PLATELETS
血小板上新型 RGD 结合膜蛋白
- 批准号:
3472446 - 财政年份:1989
- 资助金额:
$ 109.55万 - 项目类别:
A NOVEL RGD-BINDING MEMBRANE PROTEIN ON BLOOD PLATELETS
血小板上新型 RGD 结合膜蛋白
- 批准号:
3472447 - 财政年份:1989
- 资助金额:
$ 109.55万 - 项目类别:
NOVEL RGD-BINDING MEMBRANE PROTEIN ON BLOOD PLATELETS
血小板上新型 RGD 结合膜蛋白
- 批准号:
3472444 - 财政年份:1989
- 资助金额:
$ 109.55万 - 项目类别:














{{item.name}}会员




