Ubiquitination, Intestinal Homeostasis and Cancer

泛素化、肠道稳态和癌症

基本信息

批准号：
10522777
负责人：
AVERIL I MA
金额：
$ 44.86万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10522777
关键词：
Adoptive Cell Transfers Adult Bar Codes Binding Biochemical Cell Differentiation process Cell physiology Cells Chronic Colon Carcinoma Colonic Polyps Data Enterocolitis Enzymes Epithelial Epithelial Cells Genetic Epistasis Homeostasis Human Immune Inflammation Inflammation Mediators Interferons Interleukin-17 Interleukins Intestinal Cancer Intestinal Neoplasms Intestines Knock-in Mouse Lead Length Life Light Lymphocyte Malignant - descriptor Malignant Neoplasms Mediating Molecular Mus Population Predisposition Process Proliferating Proteomics Radiation Chimera Risk Role Small Intestinal Polyp T-Lymphocyte Testing Tissue Preservation Tissues Ubiquitin Ubiquitination cell transformation colitis associated cancer colon cancer prevention colorectal cancer risk cytokine gut inflammation in vivo intercellular communication interleukin-22 intestinal epithelium intestinal homeostasis mouse model novel paracrine preservation single-cell RNA sequencing transcriptomics

项目摘要

Abstract Adult intestinal tissues are maintained in a normal functional state despite rapidly proliferating and differentiating intestinal epithelial cell populations that replenish the epithelium layer every 6-7 days. Intestinal epithelial cells reside in close association with both adaptive and innate immune cells of the gut. A reciprocal and dynamic dialogue among these components maintains intestinal homeostasis and is mediated in part by paracrine cytokine and interleukin networks. Intestinal inflammation predisposes intestinal epithelial cells (IEC) to malignant transformation via incompletely understood mechanisms. We have generated a novel knock-in mouse line that spontaneously develops perturbed IEC differentiation, gut elongation, and have a high susceptibility to colon cancer. These mice provide us with a unique opportunity to discover the key inflammatory mediators that regulate intestinal homeostasis and drive IEC transformation. Using transcriptomic, proteomic, genetic epistasis and cellular approaches, our preliminary data implicate selected immune cytokines in these processes.

抽象的尽管快速增殖和增殖，但成人肠道组织仍保持正常功能状态。分化肠上皮细胞群，每 6-7 天补充一次上皮层。肠上皮细胞与肠道的适应性和先天免疫细胞密切相关。一个倒数这些成分之间的动态对话维持肠道稳态，部分是由旁分泌细胞因子和白细胞介素网络。肠道炎症易诱发肠上皮细胞 (IEC) 通过不完全了解的机制发生恶性转化。我们已经生成了一个新颖的敲入自发产生扰乱 IEC 分化、肠道伸长并具有高对结肠癌的易感性。这些小鼠为我们提供了一个独特的机会来发现关键调节肠道稳态并驱动 IEC 转化的炎症介质。使用转录组学、蛋白质组学、遗传上位性和细胞方法，我们的初步数据表明选择这些过程中的免疫细胞因子。