Fine-tuning CXCL12-mediated activities using Beta1-strand binding peptides

使用 Beta1 链结合肽微调 CXCL12 介导的活性

基本信息

  • 批准号:
    10796003
  • 负责人:
  • 金额:
    $ 46.2万
  • 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:
    2023-09-15 至 2026-09-14
  • 项目状态:
    未结题

项目摘要

ABSTRACT The CXCR4/CXCR7-CXCL12 signaling critically modulate immune and cancer cell functions. Our work and others have established the presence and the potential of chemokine heterodimers especially CXCL4-CXCL12 associated with an inhibition of CXCL12-CXCR4 signaling suggesting a new regulatory targetable mechanism. The biological consequences of these newly discovered interactions including of CXCL4-CXCL12 heterodimers with CXCR7 have not been studied yet. Further, whether CXCL4-CXCL12 chemokine hetero- dimerization may serve as a therapeutic target to prevent CXCL12-driven cell function is unknown. Therefore, we will test the hypothesis that CXCL12 ß1-strand binding peptides, mimicking the CXCL4 interface with CXCL12, critically affect signaling and biological activities in well-delineated CXCL12-CXCR4/ CXCR7 driven signaling. Specifically, we will determine the inhibiting potential of CXCL12 ß1-strand binding peptides in the CXCL12-CXCR4/CXCR7 driven signaling in macrophages and epithelial cells. The non- overlapping specific aims of the study will define binding characteristics and optimize the CXCL12 ß1- strand binding peptides (Aim 1); and determine the functional signaling modulating potential of CXCL12 ß1-strand binding peptides onto CXCR4 and CXCR7 (Aim 2), respectively. We will assess the CXCL12- CXCL12 ß1-strand binding peptide heterodimer signaling onto CXCR4 and CXCR7 associated functional activities on key cell functions, along with the optimal biophysical conditions promoting stable CXCL12- CXCL12 ß1-strand binding peptide interactions and the potential of specific CXCL12 ß1-strand binding peptides to inhibit CXCL12-CXCR4/CXCR7 signaling and modulate CXCL12-driven cell functions. Together, the data gathered through the completion of the experiments associated with the completion of the proposed aims will yield a better understanding of the CXCL12 heterodimer signaling onto CXCR4 and CXCR7 and the potential of CXCL12 ß1-strand binding peptides in preventing altering CXCL12-driven signaling and functions. Building on these results and targeting heterophilic interactions of chemokines, our long-term goal is to develop a fundamental understanding of the functions of chemokine heterodimers in chemokine signaling and their potential as target to prevent disease progression. This AREA project will expose undergraduate students to an integrative and cross-disciplinary research environment by extending training opportunities in the Departments of Biological Sciences and Physics and Optical Sciences at the University of North Carolina Charlotte, a rapidly-growing urban institution that seeks to strengthen its biomedical research program. This project has already attracted many undergraduate students through the PI’s and co-I’s classroom teaching and will further provide undergraduates a hands-on experience with laboratory research techniques and introduce them to a career in biomedical research. Students will participate in peer-to- peer training at all levels, including an emphasis on skills needed for professional success such as teamwork and communication.
摘要

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 }}

DIDIER DREAU其他文献

DIDIER DREAU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 }}

相似海外基金

Targeted ablation of cerebral atherosclerosis using supramolecular self-assembly
利用超分子自组装靶向消融脑动脉粥样硬化
  • 批准号:
    24K21101
  • 财政年份:
    2024
  • 资助金额:
    $ 46.2万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Body composition and atherosclerosis-related biomarkers in women with endometriosis
子宫内膜异位症女性的身体成分和动脉粥样硬化相关生物标志物
  • 批准号:
    23K15842
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Targeted multimodal stimuli-responsive nanogels for atherosclerosis imaging and therapy
用于动脉粥样硬化成像和治疗的靶向多模式刺激响应纳米凝胶
  • 批准号:
    2880683
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
    Studentship
The Epigenetic Regulator Prdm16 Controls Smooth Muscle Phenotypic Modulation and Atherosclerosis Risk
表观遗传调节因子 Prdm16 控制平滑肌表型调节和动脉粥样硬化风险
  • 批准号:
    10537602
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
Role of IL-6 trans signaling in atherosclerosis development and late-stage pathogenesis
IL-6反式信号传导在动脉粥样硬化发展和晚期发病机制中的作用
  • 批准号:
    10652788
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
Novel Mechanisms Underlying the Development of Atherosclerosis
动脉粥样硬化发展的新机制
  • 批准号:
    10589484
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
Alcohol Regulation of Endothelial Plasticity in Atherosclerosis
酒精对动脉粥样硬化内皮可塑性的调节
  • 批准号:
    10585070
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
From genotype to phenotype in a GWAS locus: the role of REST in atherosclerosis
GWAS 位点从基因型到表型:REST 在动脉粥样硬化中的作用
  • 批准号:
    10570469
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
2023 Atherosclerosis
2023 动脉粥样硬化
  • 批准号:
    10675221
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
The role of extracellular vesicle-associated MicroRNAs in HIV-associated atherosclerosis
细胞外囊泡相关 MicroRNA 在 HIV 相关动脉粥样硬化中的作用
  • 批准号:
    10619831
  • 财政年份:
    2023
  • 资助金额:
    $ 46.2万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了