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

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

项目成果

期刊论文数量(0)
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Joseph TY Lau其他文献

Joseph TY Lau的其他文献

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{{ 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:

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