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Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer

癌症中的先天免疫传感器、炎症小体和炎症小体介导的过程

基本信息

批准号：
10633206
负责人：
Thirumala-Devi Kanneganti
金额：
$ 105.55万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
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：
2020-07-21 至 2027-06-30
项目状态：
未结题

项目摘要

ABSTRACT Innate immune sensors and inflammasomes drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant innate immune signaling is associated with the pathogenesis of several inflammatory and metabolic diseases, neurodegeneration, and cancer. In the United States, colorectal cancer is the second most common cause of cancer deaths. Innate immunity is a major player in the colon, and thus understanding how innate immune pathways contribute to the various stages of tumor development will be key to improving cancer treatment strategies. We have an extensive track record of discoveries related to innate immune sensors and their role in colitis-associated colorectal cancer. We now seek to continue and expand this research program. The primary focus of this application is to unravel the key mechanisms of novel innate immune sensors and inflammasome regulators discovered in our lab recently and their crosstalk with cell death regulators in the development of colorectal cancer. Basic science supporting this area of research is critical to understanding the fundamentals of innate immune responses. This understanding lays the foundation to explain how defects in these sensing systems lead to the development of disease in humans. Moreover, as the molecules we are studying are central drug targets, our studies will be translated into the development of new therapeutics to treat several devastating diseases.

摘要先天性免疫传感器和炎性小体驱动免疫应答，主要提供针对以下疾病的保护：微生物感染和介导对无菌损害的控制。然而，异常的先天免疫信号是与几种炎性和代谢性疾病、神经变性和癌在美国，结直肠癌是癌症死亡的第二大常见原因。先天免疫是结肠中的主要参与者，因此了解先天免疫途径如何有助于肿瘤发展的各个阶段将是改善癌症治疗策略的关键。我们有一个广泛与先天免疫传感器及其在结肠炎相关结直肠癌中的作用有关的发现的跟踪记录。现在，我们将继续并扩大这一研究计划。本应用程序的主要重点是解开我们实验室发现的新型先天免疫传感器和炎性体调节剂的关键机制以及它们在结直肠癌发展中与细胞死亡调节因子的相互作用。基础科学支持这一研究领域对于理解先天免疫反应的基本原理至关重要。这理解为解释这些传感系统的缺陷如何导致人类的疾病。此外，由于我们正在研究的分子是中心药物靶点，我们的研究将转化为治疗几种毁灭性疾病的新疗法的发展。