Disease Initation and the role of DCs in the TRUC Model of ulcerative colitis
溃疡性结肠炎 TRUC 模型中疾病的发生和 DC 的作用
基本信息
- 批准号:8013740
- 负责人:
- 金额:$ 3.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-03-01 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:Automobile DrivingBackBiochemicalCellular biologyColitisColon CarcinomaComplexDevelopmentDiagnosisDiseaseDoctor of PhilosophyEffector CellEnteralFathersFellowshipGene-ModifiedGenesGenotypeImmune systemImmunityImmunologicsImmunologyInflammationInflammatory Bowel DiseasesInternal MedicineKnowledgeLaboratoriesLaboratory StudyLeadMalignant neoplasm of pancreasMapsMethodologyMicrobeMicrobiologyModelingMolecularMolecular BiologyMorbidity - disease rateNaturePatientsPredispositionPublic Health SchoolsRecombinant DNAResearchResidenciesRoleScanningShapesStudy modelsT-bet proteinTrainingTransgenic OrganismsUlcerative ColitisUrsidae Familyanticancer researchcommensal microbescytokinedisorder controlhigh schoolhuman diseaseinterestmicrobial communitymortalitymouse modeloncologypost-doctoral trainingtool
项目摘要
DESCRIPTION (provided by applicant): My interest in research dates back to high school when my father was diagnosed with pancreatic cancer. Lack of knowledge about and treatments for this disease led me to cancer research as an undergraduate. During my MD/PhD training, my interests broadened to encompass cell biology and immunology. These interests shaped my decision to pursue a residency in internal medicine and fellowship in oncology. During my fellowship in Dr. Laurie Glimcher's laboratory at the Harvard School of Public Health, I am studying the immunology of and role of commensal microbes in inflammatory bowel disease. My post-doctoral training will prepare me to direct a laboratory that studies the function of inflammation and microbes in colon cancer.
We have developed a mouse model of ulcerative colitis (UC) that resembles the human disease. Loss of T-bet in the innate immune system results in spontaneous and communicable UC, in the absence of adaptive immunity (termed TRUC) and increased susceptibility to colitis in immunologically intact hosts. I propose to 1 ) determine whether dendritic cells (DCs) are necessary for TRUC colitis and the factors recruiting DCs to TRUC colons 2) probe the role of the epithelial barrier and the microbiota in TRUC and 3) determine the bacterial-derived signals activating DCs in TRUC. Aim 1 will focus on the role of T-bet and colonic DCs and employs transgenic approaches to prove that the DC is the effector cell necessary and sufficient for colitis in TRUC. Employing both cell biological and microbiological approaches, I will thoroughly interrogate the epithelial barrier and key, pro-inflammatory microbes in this colitis. Using both bacterial derived products and mouse models, I will seek to determine the bacterial derived signals activating DCs in TRUC colitis.
RELEVANCE: Inflammatory bowel diseases are devastating illnesses that cause significant morbidity and mortality. We have generated a mouse model of ulcerative colitis that bears a great resemblance to the human disease. Studies of this model will hopefully lead to the identification of new therapies for patients with these diseases.
描述(由申请人提供):我对研究的兴趣可以追溯到高中时,我的父亲被诊断出患有胰腺癌。缺乏对这种疾病的知识和治疗方法使我在本科时从事癌症研究。在我的MD/PhD培训期间,我的兴趣扩大到包括细胞生物学和免疫学。这些兴趣塑造了我追求内科住院医师和肿瘤学奖学金的决定。在哈佛公共卫生学院劳里·格利姆彻博士的实验室工作期间,我正在研究肠道微生物在炎症性肠病中的免疫学和作用。我的博士后培训将使我准备好领导一个研究炎症和微生物在结肠癌中的作用的实验室。
我们已经开发了一种类似于人类疾病的溃疡性结肠炎(UC)小鼠模型。先天免疫系统中T-bet的缺失导致自发性和传染性UC,在缺乏适应性免疫(称为TRUC)的情况下,并且在免疫完整的宿主中增加对结肠炎的易感性。我建议1)确定树突状细胞(DC)是否是TRUC结肠炎所必需的,以及将DC募集到TRUC结肠的因素2)探测TRUC中上皮屏障和微生物群的作用,3)确定TRUC中激活DC的细菌源性信号。 目的1将着重于T-bet和结肠DC的作用,并采用转基因方法来证明DC是TRUC中结肠炎所必需和足够的效应细胞。采用细胞生物学和微生物学的方法,我将彻底询问上皮屏障和关键,促炎微生物在这个结肠炎。使用细菌衍生的产物和小鼠模型,我将寻求确定TRUC结肠炎中激活DC的细菌衍生的信号。
相关性:炎症性肠病是一种破坏性疾病,可导致显著的发病率和死亡率。我们已经建立了一个溃疡性结肠炎的小鼠模型,它与人类疾病非常相似。对该模型的研究有望为这些疾病的患者找到新的治疗方法。
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(2)
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Wendy S. Garrett其他文献
Immune recognition of microbial metabolites
微生物代谢物的免疫识别
- DOI:
10.1038/s41577-019-0252-2 - 发表时间:
2019-11-25 - 期刊:
- 影响因子:60.900
- 作者:
Wendy S. Garrett - 通讯作者:
Wendy S. Garrett
Bacteria in cancer initiation, promotion and progression
癌症发生、促进和进展中的细菌
- DOI:
10.1038/s41568-023-00594-2 - 发表时间:
2023-07-03 - 期刊:
- 影响因子:66.800
- 作者:
Geniver El Tekle;Wendy S. Garrett - 通讯作者:
Wendy S. Garrett
The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function
代谢传感器 LKB1 调节 ILC3 稳态和线粒体功能
- DOI:
10.1016/j.celrep.2025.115456 - 发表时间:
2025-04-22 - 期刊:
- 影响因子:6.900
- 作者:
Diogo Fonseca-Pereira;Sena Bae;Slater L. Clay;Monia Michaud;Meghan H. MacDonald;Jonathan N. Glickman;Wendy S. Garrett - 通讯作者:
Wendy S. Garrett
Engineered emEscherichia coli/em for the emin situ/em secretion of therapeutic nanobodies in the gut
用于肠道中治疗性纳米抗体原位分泌的工程化大肠杆菌
- DOI:
10.1016/j.chom.2023.03.007 - 发表时间:
2023-04-12 - 期刊:
- 影响因子:18.700
- 作者:
Jason P. Lynch;Coral González-Prieto;Analise Z. Reeves;Sena Bae;Urmila Powale;Neha P. Godbole;Jacqueline M. Tremblay;Florian I. Schmidt;Hidde L. Ploegh;Vikram Kansra;Jonathan N. Glickman;John M. Leong;Charles B. Shoemaker;Wendy S. Garrett;Cammie F. Lesser - 通讯作者:
Cammie F. Lesser
Microbiota organization—a key to understanding CRC development
微生物群结构——理解 CRC 发展的关键
- DOI:
10.1038/nrgastro.2015.25 - 发表时间:
2015-02-17 - 期刊:
- 影响因子:51.000
- 作者:
Georgina L. Hold;Wendy S. Garrett - 通讯作者:
Wendy S. Garrett
Wendy S. Garrett的其他文献
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{{ truncateString('Wendy S. Garrett', 18)}}的其他基金
Designer Probiotics for the treatment of intestinal infection and inflammation
用于治疗肠道感染和炎症的设计师益生菌
- 批准号:
9356497 - 财政年份:2016
- 资助金额:
$ 3.08万 - 项目类别:
Designer Probiotics for the treatment of intestinal infection and inflammation
用于治疗肠道感染和炎症的设计师益生菌
- 批准号:
9769017 - 财政年份:2016
- 资助金额:
$ 3.08万 - 项目类别:
Designer Probiotics for the treatment of intestinal infection and inflammation
用于治疗肠道感染和炎症的设计师益生菌
- 批准号:
10004029 - 财政年份:2016
- 资助金额:
$ 3.08万 - 项目类别:
Gut microbiota and inflammatory monocytes in colorectal cancer
结直肠癌中的肠道微生物群和炎症单核细胞
- 批准号:
8816042 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology
结直肠癌发生和具核梭杆菌:致癌微生物、致癌代谢物和肿瘤免疫学
- 批准号:
9977924 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology
结直肠癌发生和具核梭杆菌:致癌微生物、致癌代谢物和肿瘤免疫学
- 批准号:
10665786 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology
结直肠癌发生和具核梭杆菌:致癌微生物、致癌代谢物和肿瘤免疫学
- 批准号:
10207518 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Gut microbiota and inflammatory monocytes in colorectal cancer
结直肠癌中的肠道微生物群和炎症单核细胞
- 批准号:
8444653 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Gut microbiota and inflammatory monocytes in colorectal cancer
结直肠癌中的肠道微生物群和炎症单核细胞
- 批准号:
8607163 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
Colorectal carcinogenesis and Fusobacterium nucleatum: oncomicrobe, oncometabolites, and oncoimmunology
结直肠癌发生和具核梭杆菌:致癌微生物、致癌代谢物和肿瘤免疫学
- 批准号:
9307232 - 财政年份:2011
- 资助金额:
$ 3.08万 - 项目类别:
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