Elucidation of mechanisms that restrict the activation of Toll-Like Receptors and the IL-1 receptor to prevent inflammatory and autoimmune diseases

阐明限制 Toll 样受体和 IL-1 受体激活以预防炎症和自身免疫性疾病的机制

• 批准号: MR/R021406/1
• 负责人: Philip Cohen
• 金额: $ 208.91万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR021406%2F1
• 关键词: Elucidation; mechanisms; restrict; activation; Toll

The immune system is vital for defense against microbial pathogens, such as bacteria and viruses, but if it is activated too strongly or cannot be switched off efficiently, it can cause serious tissue damage and lead to many inflammatory and autoimmune diseases. These diseases include arthritis, asthma, colitis, fibrosis, lupus, psoriasis and sepsis, which affect the lives of millions of people. It is therefore critical to not only understand the mechanisms that switch on the immune system, but also those that prevent it from being activated to strongly and those that switch it off again when it is no longer needed. Our research proposal builds on novel and exciting recent findings made by our research teams, which have advanced the understanding of how the immune system is kept under control and switched off. In the longer term, our research may lead to the development of improved drugs to treat inflammatory and autoimmune diseases. It may also help to treat some forms of cancer because the immune system has a key role in helping to destroy the tumour cells that cause cancer. With these aims in mind, we are working will both University researchers and pharmaceutical companies to launch and accelerate the development of new medicines to treat these diseases that target key controller proteins that our research has identified.

免疫系统对于防御细菌和病毒等微生物病原体至关重要，但如果它被激活得太强或无法有效关闭，它可能会导致严重的组织损伤并导致许多炎症和自身免疫性疾病。这些疾病包括关节炎、哮喘、结肠炎、纤维化、狼疮、牛皮癣和败血症，影响着数百万人的生活。因此，不仅要了解开启免疫系统的机制，还要了解那些阻止免疫系统被强烈激活的机制，以及那些在不再需要免疫系统时再次关闭免疫系统的机制。我们的研究提案建立在我们的研究团队最近取得的新颖而令人兴奋的发现的基础上，这些发现促进了对免疫系统如何保持控制和关闭的理解。从长远来看，我们的研究可能会导致开发出治疗炎症和自身免疫性疾病的改进药物。它也可能有助于治疗某些形式的癌症，因为免疫系统在帮助摧毁导致癌症的肿瘤细胞方面起着关键作用。考虑到这些目标，我们正在努力将大学研究人员和制药公司推出和加速新药的开发，以治疗这些疾病，目标是我们的研究已经确定的关键控制蛋白。

项目成果

Nuts and bolts of the salt-inducible kinases (SIKs).

• DOI: 10.1042/bcj20200502
• 发表时间: 2021-04-16
• 期刊: The Biochemical journal
• 作者: Darling NJ;Cohen P
• 通讯作者: Cohen P

The scientific career and life of Edmond H. Fischer-A personal tribute.

埃德蒙·H·费舍尔的科学事业和一生——个人致敬。

• DOI: 10.1002/iub.2695
• 发表时间: 2023
• 期刊: IUBMB life
• 影响因子: 4.6
• 作者: Cohen P

Salt-inducible kinases are required for the IL-33-dependent secretion of cytokines and chemokines in mast cells.

• DOI: 10.1016/j.jbc.2021.100428
• 发表时间: 2021-01
• 期刊: The Journal of biological chemistry
• 作者: Darling NJ;Arthur JSC;Cohen P
• 通讯作者: Cohen P

Kinase drug discovery 20 years after imatinib: progress and future directions.

伊马替尼20年后的激酶药物发现：进步和未来方向。

• DOI: 10.1038/s41573-021-00195-4
• 发表时间: 2021-07
• 期刊: Nature reviews. Drug discovery
• 作者: Cohen P;Cross D;Jänne PA
• 通讯作者: Jänne PA

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

• DOI: 10.1126/scitranslmed.aba4627
• 发表时间: 2021-07-14
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Chrysostomou S;Roy R;Prischi F;Thamlikitkul L;Chapman KL;Mufti U;Peach R;Ding L;Hancock D;Moore C;Molina-Arcas M;Mauri F;Pinato DJ;Abrahams JM;Ottaviani S;Castellano L;Giamas G;Pascoe J;Moonamale D;Pirrie S;Gaunt C;Billingham L;Steven NM;Cullen M;Hrouda D;Winkler M;Post J;Cohen P;Salpeter SJ;Bar V;Zundelevich A;Golan S;Leibovici D;Lara R;Klug DR;Yaliraki SN;Barahona M;Wang Y;Downward J;Skehel JM;Ali MMU;Seckl MJ;Pardo OE
• 通讯作者: Pardo OE