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

• 批准号: 8038457
• 负责人: Wendy S. Garrett
• 金额: $ 12.52万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/8038457
• 关键词: Animal Model; Back; Bacteria; Binding; Biological; Bone Marrow; Cell Death; Cell physiology; Cells; Cellular biology; Chronic; Colitis; Colon Carcinoma; Crohn' s disease; Death Rate; Dendritic Cells; Diagnosis; Disease; Doctor of Philosophy; Effector Cell; Epithelial; Epithelial Cells; Event; Fathers; Fellowship; Functional disorder; Immune; Immune system; Immunology; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Internal Medicine; Knowledge; Laboratories; Laboratory Study; Lead; Maintenance; Malignant neoplasm of pancreas; Microbe; Modeling; Molecular; Morbidity - disease rate; Mus; Pathogenesis; Pathologic; Patients; Pattern; Pattern recognition receptor; Population; Predisposition; Principal Investigator; Production; Public Health Schools; Recruitment Activity; Research; Residencies; Role; Shapes; Signal Transduction; Study models; TNF gene; Training; Transgenic Organisms; Ulcerative Colitis; Ursidae Family; adaptive immunity; anticancer research; commensal microbes; high school; human disease; in vitro Assay; in vivo; insight; interest; intestinal epithelium; mortality; mouse model; novel; oncology; pathogen; post-doctoral training; prevent; promoter; receptor; response

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期，当时我父亲被诊断出患有胰腺癌。由于缺乏对这种疾病的了解和治疗方法，我在本科时开始了癌症研究。在我的医学博士/博士培训期间，我的兴趣扩展到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。在哈佛大学公共卫生学院劳里·格里姆彻博士的实验室学习期间，我正在研究共生微生物在炎症性肠病中的免疫学和作用。我的博士后训练将为我指导一个研究炎症和微生物在结肠癌中的作用的实验室做准备。