Transcriptional regulation of the Notch and Vegf signalling pathways during angiogenesis and arterio-venous differentiation

血管的正确形成对人类的发展和健康至关重要。然而，血管生长或形成的错误在许多疾病中都会发生。例如，实体肿瘤的发展涉及到肿瘤中新血管的生长，以提供所需的营养，而许多眼病是由视网膜血管生长缺陷引起的。因此，增加我们对血管形成和生长是如何控制的理解是非常重要的。血管的生长需要大量基因的精确调控，而我们的实验室正是在研究这种调控。特别是，我们感兴趣的是基因是如何在血管中特定开启，但在其他组织中保持关闭的。这个MRC项目将研究一组相关基因的调节，这些基因组成了血管中的Notch和VEGF信号通路。这些途径是不同的，但又是相关的，血管从周围环境接收信息，表明需要形成新的血管，以及所需的血管类型。例如，如果一个组织缺乏氧气，因此需要更多的血管，它将利用这两条途径(以及其他途径)来发出这一需求的信号。我们正在研究的两个过程是血管生成，即新血管首先形成的过程，以及动脉和静脉如何成熟。这项工作的好处将包括大幅增加我们对如何控制形成新血管的信号过程以及如何调节血管生长和分化过程的理解。预计这一结果将有助于推动预防、改变或鼓励许多不同疾病的血管生长的治疗方法的开发，包括癌症、眼病、炎性和自身免疫性疾病以及心脏病。

The correct formation of blood vessels is essential for human development and health. However, mistakes in vessel growth or formation occur in a large variety of diseases. For example, the development of solid tumours involves the growth of new blood vessels into the tumour to provide the required nutrients, and a number of eye diseases are caused by faulty blood vessel growth in the retina. Consequently, it is very important that we increase our understanding of how the formation and growth of blood vessels is controlled. The growth of blood vessels requires the precise regulation of a large number of genes, and it is this regulation that our laboratory investigates. In particular, we are interested in how genes are specifically switched on in blood vessels but remain off in other tissues. This MRC project will investigate the regulation of a group of related genes that make up the Notch and VEGF signalling pathways in blood vessels. These pathways are different, but related, ways in which blood vessels receive information from their surroundings suggesting that a new blood vessel needs to be formed, and the type of vessel that is needed. For example, if a tissue is short of oxygen and therefore wants more blood vessels, it will utilise these two pathways (and others) to signal this need. The two processes we are investigating are angiogenesis, which is the process by which new vessels first form, and how arteries and veins mature.The benefits stemming from this work will include a massive increase in our understanding of how the process of signalling to form new vessels is controlled, and how the processes of vessel growth and differentiation are regulated. It is anticipated that the results will help drive forward the development of therapies to prevent, alter or encourage vascular growth in many different diseases, including cancer, eye disease, inflammatory and autoimmune disorders, and heart disease.