Novel signaling molecules regulating platelet activation
调节血小板活化的新型信号分子
基本信息
- 批准号:10611919
- 负责人:
- 金额:$ 92.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AgeApplications GrantsAtherosclerosisBlood PlateletsBlood VesselsBlood flowCellsChronic Lymphocytic LeukemiaDiabetes MellitusDiseaseEnvironmentEventFocus GroupsFundingGeneticGoalsHemostatic functionInflammationLesionMalignant NeoplasmsMediatingMicroRNAsPaperPathway interactionsPlatelet ActivationPlayPredispositionProtein KinaseProtein Tyrosine KinasePublishingReagentRegulationResearchRoleSignal PathwaySignal TransductionSignaling MoleculeSurfaceSystemTEC Protein Tyrosine KinaseTherapeutic AgentsThrombocytopeniaThrombosisTyrosine PhosphorylationUnited States National Institutes of HealthWorkinsightkinase inhibitorlymphatic vesselnew therapeutic targetnovelplatelet functionreceptorreceptor-mediated signalingthrombotictool
项目摘要
Platelets play a crucial role in hemostasis and thrombosis, and more and more studies indicate their
role in other disease states including inflammation, cancer, and atherosclerosis Platelets express a
number of surface receptors, which through their activation, allow platelets to interpret their local
environment and to detect vascular lesions and promote hemostasis. My group focuses on these
signaling steps and how their interplay mediates platelet activation. Understanding signaling networks
and their regulation has been my research focus for the past two decades and our group has made
important contributions to the platelet-signaling field. My research goals are to identify novel signaling
molecules that regulate main signaling pathways, characterize novel signaling pathways emanating
from the same signaling molecule, and understand the differences in various tyrosine kinase
pathways in platelets. My additional goals are to understand what changes occur in platelet
composition, including miRNAs, with age and disease, such as diabetes, that make them more
susceptible to thrombotic events. This work builds on our past contributions in the field and a host of
reagents and genetic tools that we have amassed. In this proposal, we place particular emphasis on
the intracellular interactions that regulate a signaling molecule. One of the novelties of the studies
proposed is that the same protein kinase, through differential tyrosine phosphorylation, activates
diverse signaling pathways, which have distinct roles in hemostasis. The studies proposed in this
application will provide further insights into the regulation and identification of novel signaling
pathways in platelets, which may be applicable to other cell systems expressing similar receptors and
could form the basis for novel therapeutic targets to treat thrombosis and thrombocytopenia. In
addition, understanding these signaling cascades in platelets will help us evaluate and predict
possible implications of the therapeutic agents that could interfere with these pathways. For example,
our studies anticipate that Ibrutinib, a Tec kinase inhibitor used for the treatment of chronic
lymphocytic leukemia, will block the CLEC2 pathway in platelets and cause blood flow into lymphatic
vessels. I would like to pursue these goals in the next decade with the same vigor and intensity that
have employed in the past two decades. have been funded by NIH for about 22 years on the platelet
signaling paradigms and have published over 180 papers (on an average of 8 papers a year). The
OIA will alleviate the need to submit separate thematic grant applications to various agencies with
coherent specific aims and will allow us to make significant contributions to the understanding of
platelet signaling networks. Our overarching goal is to understand how the network of receptor-
mediated signaling can be manipulated to control platelet function.
血小板在止血和血栓形成中起着至关重要的作用,越来越多的研究表明,
在炎症、癌症和动脉粥样硬化等其他疾病中的作用
许多表面受体,通过它们的激活,允许血小板解释它们的局部
环境和检测血管病变和促进止血。我的团队专注于这些
信号步骤以及它们的相互作用如何介导血小板活化。了解信令网络
在过去的二十年里,他们的监管一直是我的研究重点,我们的团队已经做出了
对血小板信号传导领域的重要贡献。我的研究目标是找出新的信号
调节主要信号通路的分子,表征新的信号通路,
从相同的信号分子,并了解不同的酪氨酸激酶,
血小板中的通路。我的另外一个目标是了解血小板在
组成,包括miRNA,与年龄和疾病,如糖尿病,使他们更
易发生血栓事件。这项工作建立在我们过去在该领域的贡献和一系列
我们已经积累的试剂和基因工具。在本建议中,我们特别强调
调节信号分子的细胞内相互作用。这项研究的一个新奇之处是,
提出的是,相同的蛋白激酶,通过不同的酪氨酸磷酸化,激活
不同的信号通路,在止血中具有不同的作用。本报告中提出的研究
应用将提供进一步的见解调控和识别新的信号
这可能适用于表达类似受体的其他细胞系统,
可以形成治疗血栓形成和血小板减少症的新治疗靶点的基础。在
此外,了解血小板中的这些信号级联将有助于我们评估和预测
可能干扰这些途径的治疗剂的可能影响。比如说,
我们的研究预期,用于治疗慢性前列腺炎的Tec激酶抑制剂,
淋巴细胞白血病,将阻断血小板中的CLEC 2通路,并导致血液流入淋巴细胞,
船舶.我希望在未来十年以同样的活力和强度追求这些目标,
在过去二十年中雇用过。已经被NIH资助了22年
信令范式,发表论文180多篇(平均每年8篇)。的
内审办将减少向各机构分别提交专题赠款申请的需要,
明确的具体目标,并将使我们能够为理解
血小板信号网络我们的首要目标是了解受体网络-
可以操纵介导的信号传导以控制血小板功能。
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)
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Satya P. Kunapuli其他文献
The Third Extracellular Loop of the μ Opioid Receptor Is Important for Agonist Selectivity
- DOI:
10.1016/s0021-9258(18)92233-7 - 发表时间:
1995-06-02 - 期刊:
- 影响因子:
- 作者:
Ji-Chun Xue;Chongguang Chen;Jinmin Zhu;Satya P. Kunapuli;J. Kim de Riel;Lei Yu;Lee-Yuan Liu-Chen - 通讯作者:
Lee-Yuan Liu-Chen
Satya P. Kunapuli的其他文献
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{{ truncateString('Satya P. Kunapuli', 18)}}的其他基金
Novel signaling molecules regulating platelet activation
调节血小板活化的新型信号分子
- 批准号:
10851106 - 财政年份:2023
- 资助金额:
$ 92.87万 - 项目类别:
Novel signaling molecules regulating platelet activation
调节血小板活化的新型信号分子
- 批准号:
10393576 - 财政年份:2021
- 资助金额:
$ 92.87万 - 项目类别:
Regulation and function of PDK1-Akt-Pyk2 axis in platelets
血小板 PDK1-Akt-Pyk2 轴的调节和功能
- 批准号:
9088501 - 财政年份:2013
- 资助金额:
$ 92.87万 - 项目类别:
Regulation and function of PDK1-Akt-Pyk2 axis in platelets
血小板 PDK1-Akt-Pyk2 轴的调节和功能
- 批准号:
8707878 - 财政年份:2013
- 资助金额:
$ 92.87万 - 项目类别:
Regulation and function of PDK1-Akt-Pyk2 axis in platelets
血小板 PDK1-Akt-Pyk2 轴的调节和功能
- 批准号:
8876781 - 财政年份:2013
- 资助金额:
$ 92.87万 - 项目类别:
Regulation and function of PDK1-Akt-Pyk2 axis in platelets
血小板 PDK1-Akt-Pyk2 轴的调节和功能
- 批准号:
8580272 - 财政年份:2013
- 资助金额:
$ 92.87万 - 项目类别: