Inhibition of T-bet-mediated transcriptional elongation as a novel therapeutic target for inflammatory bowel disease.

抑制 T-bet 介导的转录延伸作为炎症性肠病的新治疗靶点。

• 批准号: MR/S00033X/1
• 负责人: Omer Serhan Omer
• 金额: $ 33.15万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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%2FS00033X%2F1
• 关键词: Inhibition; bet; mediated; transcriptional; elongation

Inflammatory bowel disease (IBD) is a condition that can lead to distressing symptoms including bloody diarrhoea, abdominal pain and weight loss. Complications of IBD include cancer, intestinal failure and bowel perforation requiring emergency surgery. Even with the most effective of treatments, a large proportion of patient's fail to respond and continue to suffer with debilitating symptoms. We are interested in discovering more targeted therapies that may ultimately benefit these patients.We believe that IBD is caused by over-activity of the immune system, particularly in the gut. A protein called T-bet plays a fundamental role in maintaining a healthy and regulated immune system. Research has shown that some patients with IBD have abnormal T-bet activity and that this may lead to immune over-activity and ultimately IBD.We would like to test the effects of blocking the activity of T-bet with new experimental treatments to see if this can treat IBD. We will initially treat mice with IBD to ensure the treatment is safe and effective before studying the effects on colonic specimens from patients with IBD. We hope to discover a new and effective treatment that can be developed, tested and benefit patients in the future.

炎症性肠病 (IBD) 是一种可导致令人痛苦的症状的疾病，包括血性腹泻、腹痛和体重减轻。 IBD 的并发症包括癌症、肠衰竭和需要紧急手术的肠穿孔。即使采用最有效的治疗方法，很大一部分患者仍无法做出反应并继续遭受衰弱症状的困扰。我们有兴趣发现更多的靶向疗法，最终可能使这些患者受益。我们认为 IBD 是由免疫系统过度活跃引起的，特别是肠道免疫系统。一种名为 T-bet 的蛋白质在维持健康和受调节的免疫系统方面发挥着重要作用。研究表明，一些 IBD 患者存在异常的 T-bet 活性，这可能会导致免疫过度活动，最终导致 IBD。我们希望通过新的实验疗法来测试阻断 T-bet 活性的效果，看看这是否可以治疗 IBD。我们将首先对 IBD 小鼠进行治疗，以确保治疗安全有效，然后再研究对 IBD 患者结肠标本的影响。我们希望发现一种新的、有效的治疗方法，可以在未来进行开发、测试并造福患者。

项目成果

Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease.

• DOI: 10.1016/j.jcmgh.2022.05.011
• 发表时间: 2022
• 期刊: CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
• 影响因子: 7.2
• 作者: Omer, Omer S.;Hertweck, Arnulf;Roberts, Luke B.;Lo, Jonathan W.;Clough, Jennie N.;Jackson, Ian;Pantazi, Eirini D.;Irving, Peter M.;MacDonald, Tom T.;Pavlidis, Polychronis;Jenner, Richard G.;Lord, Graham M.
• 通讯作者: Lord, Graham M.