An in depth study of mast cell tryptase as a novel mediator in colitis

肥大细胞类胰蛋白酶作为结肠炎新型介质的深入研究

基本信息

  • 批准号:
    8445257
  • 负责人:
  • 金额:
    $ 15.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-01 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Although there have been significant recent gains into our understanding of what causes Inflammatory Bowel Disease (IBD), there are voids in our knowledge and treatment options may be limited for certain patients. The mast cell is an effector immune cell that resides in the intestine and plays an important role in innate immunity. Although it has been thought to be important based on its increased presence in inflamed segments of intestinal tissue, its role is largely unknown. I have determined that a mediator released from activated mast cells, mouse mast cell protease-6 (mMCP- 6), plays an essential pro-inflammatory role in chemically-induced colitis in mice. The human ortholog to mMCP-6 is Tryptase-¿1 which is the dominant mast cell tryptase in humans. Based on published studies from our group and my preliminary data, I hypothesize that mMCP-6 acts to alter the permeability of the epithelial barrier and to bring neutrophils to the site of inflammation. I willuse strains of mice we have created to lack expression of mMCP-6 in various colitis models, in vitro studies using cultured mast cells and epithelial cells, and recombinant mouse and human mast cell tryptase to extensively study the mechanism of action of mast cell tryptase in colitis. I also will test an inhibitor of mMCP-6 which may have future therapeutic significance for patients with IBD. I will perform these studies in an Institution where every resource is available to me including facilities, mentors, collaborators, and advisers. In this environment and with the guidance of my mentors and collaborators, I will be poised to attain my goal of becoming an independent investigator.
描述(由申请人提供):虽然我们最近对炎症性肠病(IBD)的病因有了很大的了解,但我们的知识存在空白,某些患者的治疗选择可能有限。肥大细胞是存在于肠道中的效应免疫细胞,在先天免疫中起重要作用。虽然它被认为是重要的基础上,它的存在增加发炎段肠组织,其作用在很大程度上是未知的。我已经确定,从激活的肥大细胞释放的介质,小鼠肥大细胞蛋白酶-6(mMCP- 6),在小鼠化学诱导的结肠炎中起着重要的促炎作用。mMCP-6的人类直系同源物是类胰蛋白酶-1,其是人类中主要的肥大细胞类胰蛋白酶。根据我们小组发表的研究和我的初步数据,我假设mMCP-6的作用是改变上皮屏障的通透性,并将中性粒细胞带到炎症部位。我将使用我们在各种结肠炎模型中建立的缺乏mMCP-6表达的小鼠品系,使用培养的肥大细胞和上皮细胞以及重组小鼠和人肥大细胞类胰蛋白酶进行体外研究,以广泛研究肥大细胞类胰蛋白酶在结肠炎中的作用机制。我也 将测试mMCP-6的抑制剂,其可能对IBD患者具有未来的治疗意义。 我将在一个机构进行这些研究,其中每一个资源都提供给我,包括设施,导师,合作者和顾问。在这样的环境中,在我的导师和合作者的指导下,我将准备好实现我成为一名独立调查员的目标。

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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Matthew J Hamilton其他文献

Inactivation of Clostridioides Difficile Spores in Carpeting and Upholstery to Reduce Disease Recurrence in Households and Nursing Care Facilities
灭活地毯和室内装潢中的艰难梭菌孢子,以减少家庭和护理机构中的疾病复发
  • DOI:
    10.33790/jphip1100189
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Michael J Sadowsky;Raymond Erickson;Ping Wang;Matthew J Hamilton;Melissa Hoo;T. Kaiser;K. Fryxell;A. Khoruts
  • 通讯作者:
    A. Khoruts
Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management.
肥大细胞激活综合征和肠道功能障碍:诊断和治疗。
  • DOI:
    10.1007/s11894-024-00924-w
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Matthew J Hamilton
  • 通讯作者:
    Matthew J Hamilton
Molecular profiling of visible polypoid and invisible conventional intestinal-type low-grade dysplasia in patients with idiopathic inflammatory bowel disease.
特发性炎症性肠病患者可见息肉样和不可见常规肠型低度不典型增生的分子谱分析。
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Alexander Christakis;Jonathan Nowak;Matthew J Hamilton;J. Goldblum;Paige H. Parrack;Neal I Lindeman;R. Odze;Deepa T. Patil
  • 通讯作者:
    Deepa T. Patil

Matthew J Hamilton的其他文献

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{{ truncateString('Matthew J Hamilton', 18)}}的其他基金

An in depth study of mast cell tryptase as a novel mediator in colitis
肥大细胞类胰蛋白酶作为结肠炎新型介质的深入研究
  • 批准号:
    8281071
  • 财政年份:
    2012
  • 资助金额:
    $ 15.72万
  • 项目类别:
An in depth study of mast cell tryptase as a novel mediator in colitis
肥大细胞类胰蛋白酶作为结肠炎新型介质的深入研究
  • 批准号:
    8895307
  • 财政年份:
    2012
  • 资助金额:
    $ 15.72万
  • 项目类别:
An in depth study of mast cell tryptase as a novel mediator in colitis
肥大细胞类胰蛋白酶作为结肠炎新型介质的深入研究
  • 批准号:
    8721406
  • 财政年份:
    2012
  • 资助金额:
    $ 15.72万
  • 项目类别:
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