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

摘要 先天免疫感受器和炎症体驱动免疫反应，主要提供对 微生物感染和对无菌侮辱的中介控制。然而，异常的先天性免疫信号是 与几种炎症性和代谢性疾病、神经变性和 癌症。在美国，结直肠癌是癌症死亡的第二大常见原因。先天的 免疫是结肠中的一个主要角色，因此了解先天免疫途径如何有助于 肿瘤发展的不同阶段将是改进癌症治疗策略的关键。我们有一个广泛的 与先天性免疫感受器相关的发现及其在结肠炎相关性结直肠癌中的作用的跟踪记录。 我们现在寻求继续并扩大这一研究计划。此应用程序的主要关注点是解开 本实验室发现的新型先天免疫感受器和炎症体调节剂的关键机制 最近及其与细胞死亡调节因子在结直肠癌发展中的相互作用。基础科学 支持这一领域的研究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中的缺陷如何导致 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，我们的研究将是 转化为治疗几种毁灭性疾病的新疗法的开发。

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.