Identifying a Wnt pathway inhibitor for stem cell maintenance in IBD

炎症性肠病(IBD)是影响全球约500万人的主要医疗负担。溃疡性结肠炎(UC)是IBD的主要形式之一，影响结肠(大肠)。肠道内层溃疡使结肠发炎，导致剧烈腹痛、持续性腹泻、恶心、疲劳和发烧。在严重情况下，可能需要紧急手术。这是一种慢性(长期的)情况，但当治疗有效时，患者将会有一段时间没有症状。不幸的是，只有不到一半的UC患者对目前的治疗没有反应。此外，暴露在慢性炎症中的UC患者一生中有三分之一的风险患结直肠癌。因此，迫切需要更成功的治疗来提高患者的生活质量和结果。在IBD患者中，炎症的肠道组织无法修复，因为慢性炎症减少了负责组织修复的肠道干细胞数量。我的实验室发现了一种蛋白质，它负责调节在慢性炎症过程中负责取代受损细胞的细胞数量。在我们的项目中，我们的目标是通过灭活这种蛋白来发现治疗IBD患者的新的有效方法。首先，我们将研究其作用机制，其次，我们将测试阻断抗体(即该蛋白的失活)。这将让我们知道我们是否可以改善组织再生，从而减少炎症。我们将使用来自患者和健康志愿者的UC人体样本，这些样本将在体外创新的3D有机模型中培养，这将帮助我们了解推动疾病向前发展的机制以及如何改善组织修复。我们的发现将转化为改进的治疗方法，并将有助于改善IBD患者的健康。。

Inflammatory bowel disease (IBD) represents a major healthcare burden which affects approximately 5 million people worldwide. Ulcerative colitis (UC) is one of the main forms of IBD which affects the colon (large bowel). The colon becomes inflamed with ulcers on the inner lining of the bowel which leads to acute and severe abdominal pain, persistent diarrhoea, nausea, fatigue, and fever. In severe cases an urgent operation may be necessary. This is a chronic (long lasting) condition but when the treatment is effective there will be periods when a patient will be symptom free. Unfortunately, less than half of UC patients do not show response to current therapies. Additionally, UC patients exposed to chronic inflammation have a 1 in 3 lifetime risk of colorectal cancer. So, there is an urgent need of more successful treatments to improve patient's quality of life and outcome.In IBD patients the inflamed intestinal tissue fails to repair because chronic inflammation reduces the intestinal stem cell population which is responsible for tissue reparation. My lab has found a protein responsible to modulate the number of cells that are responsible to replace damage cells during chronic inflammation. In our project, we aim to discover novel effective approaches for treating IBD patients by inactivating this protein. First, we will study its mechanism of action and second, we will test blocking antibodies (i.e. inactivation of this protein). This will let us know if we can improve tissue regeneration and in consequence, decrease inflammation. We will use UC human samples from patients and healthy volunteers that will be cultured in an in vitro innovative 3D organoid model that will help us to understand the mechanism driving the disease forward and how to improve tissue repair. Our findings will be translated into improved treatments and will help improve IBD patient's health. .