ST6Gal-1 Sialyltransferase in Inflammation
ST6Gal-1 唾液酸转移酶在炎症中的作用
基本信息
- 批准号:10230376
- 负责人:
- 金额:$ 49.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-25 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAnti-Inflammatory AgentsAttenuatedAwarenessBacteriaBiologicalBloodCSF3 geneCell DeathCell MaintenanceCell surfaceCellsCellular biologyClinicalCommunicationDataDevelopmentDistalEffectivenessEstrogen receptor positiveEventGenerationsGlycobiologyGoalsGolgi ApparatusGranulopoiesisHematopoietic stem cellsHumanImmune TargetingIn VitroInflammationInflammatoryInflammatory ResponseInjuryIntegrinsInterventionLeftMacrophage Colony-Stimulating FactorMalignant NeoplasmsMarrowMediatingModelingMusMyelogenousMyeloid-derived suppressor cellsMyelopoiesisPathologicPathway interactionsPatient-Focused OutcomesPhenotypePhysiologicalPolysaccharidesPredispositionProductionPropertyRadioRecombinantsRegulationSepsisSialyltransferasesSignal TransductionStimulusStressSurvivorsSyndromeTestingTherapeuticTimeWorkacute symptomairway inflammationbasecytokineextracellularglycosylationglycosyltransferasein vivoinnovationinsightintravenous administrationintravenous injectionmacrophagemortalitymouse modelnovelprotective effectrecruitresponsesialylationstem cellstherapeutic development
项目摘要
PROJECT ABSTRACT
There is increasing awareness of glycans participating in the communication of critical niche-cell and cell-cell
information. A growing body of evidence implicates the 2,6-sialylation of Gal(β1,4)GlcNAc termini, mediated
by the sialyltransferase ST6Gal-1, as a central player in the regulation of diverse events including cell death,
integrin-1 function, stem cell maintenance, susceptibility to radio- and chemo-agents, myelopoiesis, and
inflammation. Canonically, glycosylation is mediated by glycosyltransferases, including ST6Gal-1, residing
within the ER-Golgi secretory apparatus of the same cells that produce them. However a significant pool of
extracellular ST6Gal-1 exists, especially in the blood. Changes in the extrinsic ST6Gal-1 pool are associated
with diverse pathologic conditions relating to stress and inflammation, and malignancies where elevated levels
generally predict poorer patient outcomes.
We observed that deficiency in circulating ST6Gal-1 results in an overly exuberant inflammatory response,
which led to the overarching hypothesis that extracellular ST6Gal-1 remodels glycans on target immune cell
surfaces, dampening response to inflammatory signals. Additional premise in support are: i) mature myeloid
and marrow hematopoietic progenitor cells are targets of extrinsic ST6Gal-1 sialylation in vivo and in vitro; ii)
extrinsic ST6Gal-1 suppresses G-CSF driven granulopoiesis; (iii) reduces M-CSF dependent generation of
macrophages; (iv) decreases inflammatory cytokine expression and release by macrophage stimulated with
LPS; and v) intravenous injection of recombinant ST6Gal-1 (rST6G) significantly ameliorates severe local and
systemic inflammation in vivo. To acquire insight into this previously overlooked glycosylation mediated
regulation of inflammation, three aims are proposed to examine i) which aspects of inflammatory cell biology
are affected by extrinsic ST6Gal-1; ii) how does extrinsic ST6Gal-1 exert this action; and iii) what is the efficacy
of rST6G in treating severe inflammation. The impact from the proposed work lies in the novelty of the
previously overlooked extrinsic glycosylation axis, the ability of extrinsic ST6Gal-1 to suppress inflammation,
and the innovation in the clinical potential of recombinant ST6Gal-1 to treat severe inflammatory conditions.
项目摘要
人们越来越认识到聚糖参与关键的微环境细胞和细胞间的通讯
信息。越来越多的证据表明 Gal(β1,4)GlcNAc 末端的 α2,6-唾液酸化介导
唾液酸转移酶 ST6Gal-1 作为细胞死亡等多种事件调节的核心角色,
整合素-1 功能、干细胞维持、对放射和化疗药物的敏感性、骨髓生成和
炎。通常,糖基化是由糖基转移酶介导的,包括 ST6Gal-1,
在产生它们的相同细胞的内质网高尔基体分泌装置内。然而,有相当数量的
细胞外存在ST6Gal-1,尤其是在血液中。外在 ST6Gal-1 池的变化与之相关
与压力和炎症相关的多种病理状况,以及水平升高的恶性肿瘤
通常预测患者的预后较差。
我们观察到循环 ST6Gal-1 的缺陷会导致过度旺盛的炎症反应,
这导致了一个总体假设:细胞外 ST6Gal-1 重塑靶免疫细胞上的聚糖
表面,抑制对炎症信号的反应。支持的其他前提是:i) 成熟的骨髓细胞
骨髓造血祖细胞是体内和体外外源性 ST6Gal-1 唾液酸化的靶标;二)
外源性 ST6Gal-1 抑制 G-CSF 驱动的粒细胞生成; (iii) 减少 M-CSF 依赖性生成
巨噬细胞; (iv) 减少巨噬细胞刺激的炎性细胞因子表达和释放
脂多糖; v) 静脉注射重组 ST6Gal-1 (rST6G) 显着改善严重的局部和
体内全身性炎症。为了深入了解这种以前被忽视的糖基化介导的
炎症的调节,提出了三个目标来检查 i) 炎症细胞生物学的哪些方面
受外源性 ST6Gal-1 影响; ii) 外源性 ST6Gal-1 如何发挥这种作用; iii) 功效是什么
rST6G 治疗严重炎症。拟议工作的影响在于其新颖性
以前被忽视的外在糖基化轴,外在 ST6Gal-1 抑制炎症的能力,
以及重组 ST6Gal-1 治疗严重炎症的临床潜力的创新。
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 }}
Joseph TY Lau其他文献
Joseph TY Lau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('Joseph TY Lau', 18)}}的其他基金
Project 2: Extracellular Glycosylation and Blood Cell Production
项目2:细胞外糖基化和血细胞生产
- 批准号:
10321581 - 财政年份:2021
- 资助金额:
$ 49.67万 - 项目类别:
Project 2: Extracellular Glycosylation and Blood Cell Production
项目2:细胞外糖基化和血细胞生产
- 批准号:
10545016 - 财政年份:2021
- 资助金额:
$ 49.67万 - 项目类别:
Project 2: Extracellular Glycosylation and Blood Cell Production
项目2:细胞外糖基化和血细胞生产
- 批准号:
10088969 - 财政年份:2021
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal-1 Sialyltransferase in Inflammation
ST6Gal-1 唾液酸转移酶在炎症中的作用
- 批准号:
10265723 - 财政年份:2020
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal-1 Sialyltransferase in Inflammation
ST6Gal-1 唾液酸转移酶在炎症中的作用
- 批准号:
10159705 - 财政年份:2020
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal-1 Sialyltransferase in Inflammation
ST6Gal-1 唾液酸转移酶在炎症中的作用
- 批准号:
9770765 - 财政年份:2018
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal I sialyltransferase in hematopoiesis
ST6Gal I 唾液酸转移酶在造血中的作用
- 批准号:
8452723 - 财政年份:2011
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal I sialyltransferase in hematopoiesis
ST6Gal I 唾液酸转移酶在造血中的作用
- 批准号:
8827236 - 财政年份:2011
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal I sialyltransferase in hematopoiesis
ST6Gal I 唾液酸转移酶在造血中的作用
- 批准号:
8645582 - 财政年份:2011
- 资助金额:
$ 49.67万 - 项目类别:
ST6Gal I sialyltransferase in hematopoiesis
ST6Gal I 唾液酸转移酶在造血中的作用
- 批准号:
8185890 - 财政年份:2011
- 资助金额:
$ 49.67万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 49.67万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 49.67万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 49.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 49.67万 - 项目类别:
Studentship














{{item.name}}会员




